biphenyl compounds

Summary

Top Publications

  1. ncbi An inhibitor of Bcl-2 family proteins induces regression of solid tumours
    Tilman Oltersdorf
    Idun Pharmaceuticals, 9380 Judicial Drive, San Diego, California 92121, USA
    Nature 435:677-81. 2005
  2. pmc The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized
    Mark F van Delft
    The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia
    Cancer Cell 10:389-99. 2006
  3. ncbi Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members
    Michael Certo
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Cancer Cell 9:351-65. 2006
  4. pmc Bcl-2 inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy
    Min H Kang
    Cancer Center and the Department of Cell Biology and Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USA
    Clin Cancer Res 15:1126-32. 2009
  5. ncbi Programmed anuclear cell death delimits platelet life span
    Kylie D Mason
    Molecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia
    Cell 128:1173-86. 2007
  6. ncbi BH3 profiling identifies three distinct classes of apoptotic blocks to predict response to ABT-737 and conventional chemotherapeutic agents
    Jing Deng
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Cancer Cell 12:171-85. 2007
  7. pmc Acquired resistance to ABT-737 in lymphoma cells that up-regulate MCL-1 and BFL-1
    Derek Yecies
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA
    Blood 115:3304-13. 2010
  8. ncbi Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia
    Marina Konopleva
    Section of Molecular Hematology and Therapy, Department of Blood and Marrow Transplantation, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Cell 10:375-88. 2006
  9. pmc Bcl-2, Bcl-x(L), and Bcl-w are not equivalent targets of ABT-737 and navitoclax (ABT-263) in lymphoid and leukemic cells
    Delphine Merino
    The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Blood 119:5807-16. 2012
  10. ncbi Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARgamma-modulating activity
    Stephen C Benson
    Department of Biological Sciences, California State University, Hayward, USA
    Hypertension 43:993-1002. 2004

Detail Information

Publications299 found, 100 shown here

  1. ncbi An inhibitor of Bcl-2 family proteins induces regression of solid tumours
    Tilman Oltersdorf
    Idun Pharmaceuticals, 9380 Judicial Drive, San Diego, California 92121, USA
    Nature 435:677-81. 2005
    ....
  2. pmc The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized
    Mark F van Delft
    The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia
    Cancer Cell 10:389-99. 2006
    ..Hence, ABT-737 should prove efficacious in tumors with low Mcl-1 levels, or when combined with agents that inactivate Mcl-1, even to treat those tumors that overexpress Bcl-2...
  3. ncbi Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members
    Michael Certo
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Cancer Cell 9:351-65. 2006
    ..Our data allow us to distinguish a cellular state we call "primed for death," which can be determined by BH3 profiling and which correlates with dependence on antiapoptotic family members for survival...
  4. pmc Bcl-2 inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy
    Min H Kang
    Cancer Center and the Department of Cell Biology and Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USA
    Clin Cancer Res 15:1126-32. 2009
    ..Here, we review the role of the Bcl-2 family in apoptotic pathways and those agents that are known and/or designed to inhibit the anti-apoptotic Bcl-2 family of proteins...
  5. ncbi Programmed anuclear cell death delimits platelet life span
    Kylie D Mason
    Molecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia
    Cell 128:1173-86. 2007
    ....
  6. ncbi BH3 profiling identifies three distinct classes of apoptotic blocks to predict response to ABT-737 and conventional chemotherapeutic agents
    Jing Deng
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Cancer Cell 12:171-85. 2007
    ..BCL-2 dependence correlates with high levels of proapoptotic BIM sequestered by BCL-2. Strikingly, BH3 profiling can also predict sensitivity to conventional chemotherapeutic agents like etoposide, vincristine, and adriamycin...
  7. pmc Acquired resistance to ABT-737 in lymphoma cells that up-regulate MCL-1 and BFL-1
    Derek Yecies
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA
    Blood 115:3304-13. 2010
    ..This dynamic increase suggests a novel mechanism whereby modulation of antiapoptotic protein function communicates with nuclear transcriptional machinery...
  8. ncbi Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia
    Marina Konopleva
    Section of Molecular Hematology and Therapy, Department of Blood and Marrow Transplantation, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Cell 10:375-88. 2006
    ..These data suggest that ABT-737 could be a highly effective antileukemia agent when the mechanisms of resistance identified here are considered...
  9. pmc Bcl-2, Bcl-x(L), and Bcl-w are not equivalent targets of ABT-737 and navitoclax (ABT-263) in lymphoid and leukemic cells
    Delphine Merino
    The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Blood 119:5807-16. 2012
    ..These results have profound implications for how BH3-mimetics induce apoptosis and how the use of these compounds can be optimized for treating lymphoid malignancies...
  10. ncbi Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARgamma-modulating activity
    Stephen C Benson
    Department of Biological Sciences, California State University, Hayward, USA
    Hypertension 43:993-1002. 2004
    ....
  11. ncbi Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes
    E J Lewis
    Department of Medicine, Rush-Presbyterian-St Luke's Medical Center, Chicago, IL 60612, USA
    N Engl J Med 345:851-60. 2001
    ..CONCLUSIONS: The angiotensin-II-receptor blocker irbesartan is effective in protecting against the progression of nephropathy due to type 2 diabetes. This protection is independent of the reduction in blood pressure it causes...
  12. ncbi Bcl-2 inhibitors: small molecules with a big impact on cancer therapy
    M Vogler
    MRC Toxicology Unit, Hodgkin Building, University of Leicester, PO Box 138, Lancaster Road, Leicester LE1 9HN, UK
    Cell Death Differ 16:360-7. 2009
    ..In in vitro studies, primary cells from patients with various B-cell malignancies are exquisitely sensitive to ABT-737, exhibiting novel morphological features of apoptosis including marked outer mitochondrial membrane rupture...
  13. ncbi Different forms of cell death induced by putative BCL2 inhibitors
    M Vogler
    MRC Toxicology Unit, Hodgkin Building, University of Leicester, Leicestershire, UK
    Cell Death Differ 16:1030-9. 2009
    ....
  14. pmc Mimicking the BH3 domain to kill cancer cells
    T Ní Chonghaile
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Oncogene 27:S149-57. 2008
    ..Thus, the BH3 mimetics are a new class of cancer drugs that specifically target a mechanism of cancer cell survival to selectively kill cancer cells...
  15. ncbi Angiotensin type 1 receptor blockers induce peroxisome proliferator-activated receptor-gamma activity
    Michael Schupp
    Center for Cardiovascular Research, Institut fur Pharmakologie und Toxikologie, Campus Charite Mitte, Charite Universitatsmedizin Berlin, Berlin, Germany
    Circulation 109:2054-7. 2004
    ..The peroxisome proliferator-activated receptor-gamma (PPARgamma) is the central regulator of insulin and glucose metabolism improving insulin sensitivity. We investigated the regulation of PPARgamma function by ARBs...
  16. pmc Therapeutic efficacy of ABT-737, a selective inhibitor of BCL-2, in small cell lung cancer
    Christine L Hann
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21231, USA
    Cancer Res 68:2321-8. 2008
    ..Taken together, these data have specific implications for the clinical development of Bcl-2 inhibitors for SCLC and broader implications for the testing of novel anticancer strategies in relevant preclinical models...
  17. ncbi Inhibition of NADPH oxidase-related oxidative stress-triggered signaling by honokiol suppresses high glucose-induced human endothelial cell apoptosis
    Meei Ling Sheu
    Institute of Medical Technology, National Chung Hsing University, Taiwan
    Free Radic Biol Med 44:2043-50. 2008
    ....
  18. ncbi The Bcl-xL inhibitor, ABT-737, efficiently induces apoptosis and suppresses growth of hepatoma cells in combination with sorafenib
    Hayato Hikita
    Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
    Hepatology 52:1310-21. 2010
    ..Sorafenib, not alone but in combination with ABT-737, efficiently induced apoptosis in hepatoma cells. This combination also led to stronger suppression of xenograft tumors than sorafenib alone...
  19. ncbi Concurrent up-regulation of BCL-XL and BCL2A1 induces approximately 1000-fold resistance to ABT-737 in chronic lymphocytic leukemia
    Meike Vogler
    Medical Research Council Toxicology Unit, University of Leicester, Leicester, United Kingdom
    Blood 113:4403-13. 2009
    ....
  20. ncbi The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes
    H H Parving
    Steno Diabetes Center, Copenhagen, Denmark
    N Engl J Med 345:870-8. 2001
    ..02). CONCLUSIONS: Irbesartan is renoprotective independently of its blood-pressure-lowering effect in patients with type 2 diabetes and microalbuminuria...
  21. ncbi Defining the target specificity of ABT-737 and synergistic antitumor activities in combination with histone deacetylase inhibitors
    Kate F Whitecross
    Cancer Immunology Program, The Peter MacCallum Cancer Centre, Trescowthick Research Laboratories, East Melbourne, Australia
    Blood 113:1982-91. 2009
    ..Our studies provide important preclinical data on the binding specificity of ABT-737 and its usefulness against primary hematologic malignancies when used as a single agent and in combination with HDACi...
  22. ncbi Free radical scavenging properties of wheat extracts
    Liangli Yu
    Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, Colorado 80523, USA
    J Agric Food Chem 50:1619-24. 2002
    ..The TPC were 487.9 +/- 927.8 microg gallic acid equivalents/g of grain. No correlation was observed between TPC and radical scavenging capacities for DPPH* and ABTS*+ (p = 0.15 and p > 0.5, respectively)...
  23. ncbi Activity of vincristine, L-ASP, and dexamethasone against acute lymphoblastic leukemia is enhanced by the BH3-mimetic ABT-737 in vitro and in vivo
    Min H Kang
    Developmental Therapeutics Program, Childrens Hospital Los Angeles and University of Southern California Institute for Pediatric Clinical Research, Los Angeles, CA 90027, USA
    Blood 110:2057-66. 2007
    ..Combining VXL with a BH3-mimetic warrants clinical investigation in ALL at relapse and potentially in chemotherapy-resistant ALL subgroups...
  24. pmc Combined Bcl-2/mammalian target of rapamycin inhibition leads to enhanced radiosensitization via induction of apoptosis and autophagy in non-small cell lung tumor xenograft model
    Kwang Woon Kim
    Department of Radiation Oncology, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 5671, USA
    Clin Cancer Res 15:6096-105. 2009
    ..Radiotherapy has a central role in the treatment of non-small cell lung cancer. Effectiveness of this modality, however, is often limited as resistance results from defects in cell death...
  25. ncbi Honokiol, a phytochemical from the Magnolia plant, inhibits photocarcinogenesis by targeting UVB-induced inflammatory mediators and cell cycle regulators: development of topical formulation
    Mudit Vaid
    Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Carcinogenesis 31:2004-11. 2010
    ..Together, our results indicate that honokiol holds promise for the prevention of UVB-induced skin cancer by targeting inflammatory mediators, cell cycle regulators and cell survival signals in UVB-exposed skin...
  26. pmc Honokiol, a multifunctional antiangiogenic and antitumor agent
    Levi E Fried
    Department of Dermatology, Emory University School of Medicine, Winship Cancer Institute, Atlanta VA Medical Center, Atlanta, Georgia 30322, USA
    Antioxid Redox Signal 11:1139-48. 2009
    ..Knowledge of the dual activities of honokiol can assist with the development of honokiol derivatives and the design of clinical trials that will maximize the potential benefit of honokiol in the patient setting...
  27. ncbi Apoptosis-based treatment of glioblastomas with ABT-737, a novel small molecule inhibitor of Bcl-2 family proteins
    K E Tagscherer
    Molecular Neuro Oncology, German Cancer Research Center, Heidelberg, Germany
    Oncogene 27:6646-56. 2008
    ..As the resistance of glioma stem cells was associated with high Mcl-1 expression levels, ABT-737 treatment combined with downregulation of Mcl-1 could represent a promising novel approach in glioblastoma treatment...
  28. pmc RNA silencing of Mcl-1 enhances ABT-737-mediated apoptosis in melanoma: role for a caspase-8-dependent pathway
    Angela M Keuling
    Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada
    PLoS ONE 4:e6651. 2009
    ..However, overexpression of Mcl-1, a frequent observance in melanoma, is known to confer ABT-737 resistance...
  29. pmc Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737
    Victoria Del Gaizo Moore
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    J Clin Invest 117:112-21. 2007
    ..Indeed, activator BH3-only occupation of BCL2 may prime cancer cells for death, offering a potential explanation for the marked chemosensitivity of certain cancers that express abundant BCL2, such as CLL and follicular lymphoma...
  30. ncbi Modulation of NOXA and MCL-1 as a strategy for sensitizing melanoma cells to the BH3-mimetic ABT-737
    Keryn M Lucas
    The Centenary Institute, Newtown, New South Wales, Australia
    Clin Cancer Res 18:783-95. 2012
    ..Melanoma cells are insensitive to ABT-737, but MCL-1 inhibition reportedly increases the sensitivity of other tumors to the compound...
  31. pmc Bim and Bad mediate imatinib-induced killing of Bcr/Abl+ leukemic cells, and resistance due to their loss is overcome by a BH3 mimetic
    Junya Kuroda
    The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia
    Proc Natl Acad Sci U S A 103:14907-12. 2006
    ..These results demonstrate that Bim and Bad account for most, perhaps all, imatinib-induced killing of Bcr/Abl+ leukemic cells and suggest previously undescribed drug combination strategies for cancer therapy...
  32. ncbi Influence of Bcl-2 family members on the cellular response of small-cell lung cancer cell lines to ABT-737
    Stephen K Tahir
    Global Pharmaceutical Product Research Division, Abbott Laboratories, Abbott Park Road, Abbott Park, IL 60064, USA
    Cancer Res 67:1176-83. 2007
    ..Overall, these observations provide further insight as to the mechanistic bases for ABT-737 efficacy in SCLC and will be helpful for profiling patients and aiding in the rational design of combination therapies...
  33. ncbi Magnolol enhances adipocyte differentiation and glucose uptake in 3T3-L1 cells
    Sun Sil Choi
    Research Institute for Biological Functions, Chubu University, 1200 Matsumoto, Kasugai, Aichi, Japan
    Life Sci 84:908-14. 2009
    ..Its ligands, including thiazolidinediones, improve insulin sensitivity in type 2 diabetes. We investigate the effect of magnolol, an ingredient of Magnolia officinalis on adipogenesis and glucose uptake using 3T3-L1 cells...
  34. pmc Dual inhibition of Bcl-2 and Bcl-xL strikingly enhances PI3K inhibition-induced apoptosis in human myeloid leukemia cells through a GSK3- and Bim-dependent mechanism
    Mohamed Rahmani
    Department of Medicine, Virginia Commonwealth University, The Virginia Institute for Molecular Medicine and Massey Cancer Center, Richmond, VA 23298, USA
    Cancer Res 73:1340-51. 2013
    ..They also argue that combining PI3K/AKT/mTOR inhibitors with BH3 mimetics warrants attention in AML, particularly in the setting of basal AKT activation and/or addiction...
  35. pmc Magnolol, a major bioactive constituent of the bark of Magnolia officinalis, exerts antiepileptic effects via the GABA/benzodiazepine receptor complex in mice
    C R Chen
    Department of Pharmacology, Shanghai Medical College, Fudan University, Shanghai, China
    Br J Pharmacol 164:1534-46. 2011
    ..The aim of this study was to evaluate the anti-convulsant effects of magnolol (6, 6', 7, 12-tetramethoxy-2, 2'-dimethyl-1-β-berbaman, C18H18O2) and the mechanisms involved...
  36. ncbi The efficacy and safety of low- and high-dose fixed combinations of irbesartan/hydrochlorothiazide in patients with uncontrolled systolic blood pressure on monotherapy: the INCLUSIVE trial
    Joel M Neutel
    Orange County Research Center, Tustin, CA 92780, USA
    J Clin Hypertens (Greenwich) 7:578-86. 2005
    ..Treatments were well tolerated. This irbesartan/HCTZ treatment regimen achieved SBP goals in more than 75% of patients uncontrolled on monotherapy...
  37. ncbi Identification of a naturally occurring rexinoid, honokiol, that activates the retinoid X receptor
    Hitoshi Kotani
    Laboratory of Medicinal Resources, School of Pharmacy, Aichi Gakuin University, 1 100 Kusumoto cho, Chikusa ku, Nagoya 464 8650, Japan
    J Nat Prod 73:1332-6. 2010
    ..The results obtained demonstrate that 1, a newly identified natural rexinoid, regulates the functions of RXR/LXR heterodimer and abrogates foam cell formation by the induction of ABCA1 via activation of the RXR/LXR heterodimer...
  38. ncbi Pharmacokinetic interaction of fimasartan, a new angiotensin II receptor antagonist, with amlodipine in healthy volunteers
    SoJeong Yi
    Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, Jongno gu, Seoul, Republic of Korea
    J Cardiovasc Pharmacol 57:682-9. 2011
    ..The objective of this study was to investigate the effect of the coadministration of fimasartan and amlodipine on the steady-state pharmacokinetics of each drug...
  39. ncbi Dichotomy in NF-kappaB signaling and chemoresistance in immunoglobulin variable heavy-chain-mutated versus unmutated CLL cells upon CD40/TLR9 triggering
    J M Tromp
    Department of Hematology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Oncogene 29:5071-82. 2010
    ..Thus, a distinction in NF-kappaB activation and drug susceptibility in mutated versus unmutated (LN-like) CLL cells was uncovered, which was causally linked to Bcl-X(L) levels...
  40. ncbi Odanacatib in the treatment of postmenopausal women with low bone mineral density: three-year continued therapy and resolution of effect
    John A Eisman
    Garvan Institute of Medical Research, St Vincent s Hospital, University of New South Wales, Sydney, NSW, Australia
    J Bone Miner Res 26:242-51. 2011
    ..Bone-resorption markers remained suppressed, whereas bone-formation markers returned to near baseline. ODN effects were reversible: bone resorption increased transiently and BMD decreased following treatment discontinuation...
  41. pmc Honokiol arrests cell cycle, induces apoptosis, and potentiates the cytotoxic effect of gemcitabine in human pancreatic cancer cells
    Sumit Arora
    Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama, United States of America
    PLoS ONE 6:e21573. 2011
    ..Altogether, these findings demonstrate, for the first time, the growth inhibitory effects of honokiol in pancreatic cancer and indicate its potential usefulness as a novel natural agent in prevention and therapy...
  42. ncbi Odanacatib treatment increases hip bone mass and cortical thickness by preserving endocortical bone formation and stimulating periosteal bone formation in the ovariectomized adult rhesus monkey
    Tara Cusick
    Bone Biology Group, Merck Sharp and Dohme Corp, West Point, PA 19486, USA
    J Bone Miner Res 27:524-37. 2012
    ..The drug provided marked increases in periosteal bone formation and cortical thickness in OVX monkeys, suggesting that CatK inhibition may represent a novel therapeutic approach for the treatment of osteoporosis...
  43. ncbi I-COMBINE study: assessment of efficacy and safety profile of irbesartan/amlodipine fixed-dose combination therapy compared with amlodipine monotherapy in hypertensive patients uncontrolled with amlodipine 5 mg monotherapy: a multicenter, phase III, prosp
    Guillaume Bobrie
    Department of Hypertension, Hopital Europeen Georges Pompidou, Paris, France
    Clin Ther 34:1705-19. 2012
    ..Newer antihypertensive treatment combinations include fixed-dose combinations of an angiotensin receptor blocker and a calcium channel blocker...
  44. ncbi Efficacy and tolerability of fimasartan, a new angiotensin receptor blocker, compared with losartan (50/100 mg): a 12-week, phase III, multicenter, prospective, randomized, double-blind, parallel-group, dose escalation clinical trial with an optional 12-w
    Sang Eun Lee
    Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
    Clin Ther 34:552-568, 568.e1-9. 2012
    ..Angiotensin receptor blockers (ARBs) is an effective and well tolerated first-line antihypertensive drug. Fimasartan is a newly developed ARB that has not been compared with other ARBs with regard to its efficacy and tolerability...
  45. pmc Efficacy and safety of fixed combinations of irbesartan/hydrochlorothiazide in hypertensive women: the inclusive trial
    Elizabeth O Ofili
    Morehouse School of Medicine, Atlanta, Georgia 30310, USA
    J Womens Health (Larchmt) 17:931-8. 2008
    ....
  46. pmc Inhibitory effect of 4-O-methylhonokiol on lipopolysaccharide-induced neuroinflammation, amyloidogenesis and memory impairment via inhibition of nuclear factor-kappaB in vitro and in vivo models
    Young Jung Lee
    College of Pharmacy, Chungbuk National University, 12, Gaeshin dong, Heungduk gu, Cheongju, Chungbuk 361 763, Korea
    J Neuroinflammation 9:35. 2012
    ..In the present study, we investigated the possible preventive effects of 4-O-methylhonokiol, a constituent of Magnolia officinalis, on memory deficiency caused by LPS, along with the underlying mechanisms...
  47. ncbi Odanacatib reduces bone turnover and increases bone mass in the lumbar spine of skeletally mature ovariectomized rhesus monkeys
    Patricia J Masarachia
    Bone Biology Group, Merck Sharp and Dohme Corp, West Point, PA 19486, USA
    J Bone Miner Res 27:509-23. 2012
    ..Taken together, our findings demonstrated that the long-term treatment with ODN effectively suppressed bone turnover without reducing osteoclast number and maintained normal biomechanical properties of the spine of OVX nonhuman primates...
  48. pmc Magnolol, a natural compound, induces apoptosis of SGC-7901 human gastric adenocarcinoma cells via the mitochondrial and PI3K/Akt signaling pathways
    Azhar Rasul
    Central Research Laboratory, Jilin University Bethune Second Hospital, Changchun 130041, PR China
    Int J Oncol 40:1153-61. 2012
    ....
  49. ncbi Unleashing the power of inhibitors of oncogenic kinases through BH3 mimetics
    Mark S Cragg
    The Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria, Australia
    Nat Rev Cancer 9:321-6. 2009
    ..Combining oncogenic kinase inhibitors with direct activators of the apoptosis machinery, such as the BH3 mimetic ABT-737, may unlock potent anti-tumour potential to produce durable clinical responses with less collateral damage...
  50. pmc Diapocynin and apocynin administration fails to significantly extend survival in G93A SOD1 ALS mice
    Kari A Trumbull
    Linus Pauling Institute, Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA
    Neurobiol Dis 45:137-44. 2012
    ..Diapocynin was also detected in the CNS of apocynin-treated mice. The failure to achieve significant protection with either apocynin or diapocynin raises questions about the utility for treating ALS patients...
  51. ncbi Anti-inflammatory effect of 4-O-methylhonokiol, compound isolated from Magnolia officinalis through inhibition of NF-kappaB [corrected]
    Ju Hoon Oh
    College of Pharmacy, CBITRC, Chungbuk National University, 12, Gaesin dong, Heungduk gu, Cheongju, Chungbuk 361 763, Republic of Korea
    Chem Biol Interact 180:506-14. 2009
    ..The present results provided evidence that 4-O-methylhonokiol has anti-inflammatory properties through inhibition of the NF-kappaB pathway, and suggested that 4-O-methylhonokiol can be used as an anti-inflammatory agent...
  52. ncbi Total polyphenol content and antioxidant capacity of commercially available tea (Camellia sinensis) in Argentina
    Claudia Anesini
    Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
    J Agric Food Chem 56:9225-9. 2008
    ..The results obtained herein allow one to conclude that Argentine tea is of very good quality when compared to teas from other sources...
  53. pmc BH3 mimetics antagonizing restricted prosurvival Bcl-2 proteins represent another class of selective immune modulatory drugs
    Emma M Carrington
    Autoimmunity and Transplantation Division, The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Australia
    Proc Natl Acad Sci U S A 107:10967-71. 2010
    ..These results provide an insight into the selective mechanisms of immune cell survival and how this selectivity avails a different strategy for immune modulation...
  54. ncbi 4-O-methylhonokiol attenuated β-amyloid-induced memory impairment through reduction of oxidative damages via inactivation of p38 MAP kinase
    Yong Kyung Lee
    College of Pharmacy and MRC, Chungbuk National University, Heungduk gu, Cheongju, Chungbuk 361 763, South Korea
    J Nutr Biochem 22:476-86. 2011
    ..These results suggest that 4-O-MH might prevent the development and progression of AD through the reduction of oxidative stress and neuronal cell death via inactivation of p38 MAP kinase pathway...
  55. pmc Sensitization of BCL-2-expressing breast tumors to chemotherapy by the BH3 mimetic ABT-737
    Samantha R Oakes
    The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia
    Proc Natl Acad Sci U S A 109:2766-71. 2012
    ..Our findings provide in vivo evidence that BH3 mimetics can be used to sensitize primary breast tumors to chemotherapy and further suggest that elevated BCL-2 expression constitutes a predictive response marker in breast cancer...
  56. pmc Honokiol is a potent scavenger of superoxide and peroxyl radicals
    Sergey Dikalov
    Division of Cardiology, Emory University School of Medicine, 1639 Pierce Drive, Suite 319 WMB, Atlanta, GA 30322, United States
    Biochem Pharmacol 76:589-96. 2008
    ..5x10(6)M(-1)s(-1)). Therefore, honokiol is an effective scavenger of both superoxide and peroxyl radicals, which may be important for physiological activity of honokiol...
  57. ncbi Honokiol causes G0-G1 phase cell cycle arrest in human prostate cancer cells in association with suppression of retinoblastoma protein level/phosphorylation and inhibition of E2F1 transcriptional activity
    Eun Ryeong Hahm
    Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Mol Cancer Ther 6:2686-95. 2007
    ....
  58. ncbi Honokiol, a natural plant product, inhibits inflammatory signals and alleviates inflammatory arthritis
    Melissa E Munroe
    Department of Microbiology, University of Iowa, IA 52242, USA
    J Immunol 179:753-63. 2007
    ..These promising findings suggest that the nontoxic anti-inflammatory properties of HNK could be valuable for blocking the autoimmune response...
  59. ncbi Characterization of neurotoxic effects of NMDA and the novel neuroprotection by phytopolyphenols in mice
    Chen Chang-Mu
    Department of Surgery, National Taiwan University Hospital, Institute of Toxicology, National Taiwan University, Taiwan
    Behav Neurosci 124:541-53. 2010
    ..The therapeutic potential of these neuroprotective regimens in treating excitotoxicity-related diseases merits for further investigation...
  60. ncbi Inhibition of diet-induced atherosclerosis and endothelial dysfunction in apolipoprotein E/angiotensin II type 1A receptor double-knockout mice
    Sven Wassmann
    Klinik fur Innere Medizin III, Universitatsklinikum des Saarlandes, Homburg Saar, Germany
    Circulation 110:3062-7. 2004
    ..Angiotensin II type 1 (AT1) receptor activation is potentially involved in the multifactorial pathogenesis of atherosclerosis...
  61. ncbi Synergistic antitumor activity of gemcitabine and ABT-737 in vitro and in vivo through disrupting the interaction of USP9X and Mcl-1
    Chong Zhang
    1Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China
    Mol Cancer Ther 10:1264-75. 2011
    ....
  62. pmc Distribution of Bim determines Mcl-1 dependence or codependence with Bcl-xL/Bcl-2 in Mcl-1-expressing myeloma cells
    Alejo A Morales
    Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, USA
    Blood 118:1329-39. 2011
    ..Overall, these results suggest that complex interactions, and not simply expression patterns of Bcl-2 proteins, need to be investigated to understand Bcl-2 dependence and how to better use agents, such as ABT-737...
  63. ncbi ABT-737 is highly effective against molecular subgroups of multiple myeloma
    Linda Bodet
    INSERM, Unité Mixte de Recherche_S892, Institut de Recherche Thérapeutique de l Université de Nantes, Nantes, France
    Blood 118:3901-10. 2011
    ....
  64. pmc Honokiol in combination with radiation targets notch signaling to inhibit colon cancer stem cells
    Sivapriya Ponnurangam
    Department of Molecular and Integrative Physiology, The University of Kansas Medical Center, Kansas City, Kansas 66160, USA
    Mol Cancer Ther 11:963-72. 2012
    ..These studies warrant further clinical evaluation for the combination of honokiol and IR for treating colon cancers...
  65. pmc Anti-inflammatory effects of the neurotransmitter agonist Honokiol in a mouse model of allergic asthma
    Melissa E Munroe
    Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
    J Immunol 185:5586-97. 2010
    ....
  66. ncbi ABT-737 induces apoptosis in mantle cell lymphoma cells with a Bcl-2high/Mcl-1low profile and synergizes with other antineoplastic agents
    Cyrille Touzeau
    INSERM UMR 892, Universite de Nantes, Nantes, France
    Clin Cancer Res 17:5973-81. 2011
    ..Mantle cell lymphoma (MCL) is considered to be incurable. ABT-737 is a BH3 mimetic that targets Bcl-2, which is overexpressed in MCL and implicated in drug resistance. The present work investigated the antitumor effect of ABT-737...
  67. pmc BCL-2 dependence and ABT-737 sensitivity in acute lymphoblastic leukemia
    Victoria Del Gaizo Moore
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 111:2300-9. 2008
    ..The ALL cells studied exhibit BCL-2 dependence, supporting clinical trials of BCL-2 antagonists in ALL as single agents or combination therapies...
  68. ncbi Concomitant inhibition of MDM2 and Bcl-2 protein function synergistically induce mitochondrial apoptosis in AML
    Kensuke Kojima
    Section of Molecular Hematology and Therapy, Department of Blood and Marrow Transplantation, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
    Cell Cycle 5:2778-86. 2006
    ..Our data suggest that combined targeting of Mdm2 and Bcl-2 proteins could offer considerable therapeutic promise in AML...
  69. pmc An antiapoptotic BCL-2 family expression index predicts the response of chronic lymphocytic leukemia to ABT-737
    Sayer Al-Harbi
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
    Blood 118:3579-90. 2011
    ..Changes after ABT-737 treatment included increased expression of BFL-1 and BCL-B that may contribute to treatment resistance. This study defines a highly significant BCL-2 expression index for predicting the response of CLL to ABT-737...
  70. ncbi Anti-inflammatory bioactivities of honokiol through inhibition of protein kinase C, mitogen-activated protein kinase, and the NF-kappaB pathway to reduce LPS-induced TNFalpha and NO expression
    Louis Kuoping Chao
    Department of Cosmeceutics, China Medical University, Taichung, Taiwan
    J Agric Food Chem 58:3472-8. 2010
    ..Our current results have exhaustively described the anti-inflammatory properties of honokiol, which could lead to the possibility of its future pharmaceutical application in the realm of immunomodulation...
  71. ncbi A novel Bcl-2/Bcl-X(L)/Bcl-w inhibitor ABT-737 as therapy in multiple myeloma
    D Chauhan
    The Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Oncogene 26:2374-80. 2007
    ....
  72. ncbi Effects of magnolol (5,5'-diallyl-2,2'-dihydroxybiphenyl) on diabetic nephropathy in type 2 diabetic Goto-Kakizaki rats
    Eun Jin Sohn
    Department of Herbal Pharmaceutical Development, Korea Institute of Oriental Medicine, 461 24 Jeonmin dong, Yuseong Gu, Daejeon 305 811, Republic of Korea
    Life Sci 80:468-75. 2007
    ..Thus based on our findings, the use of magnolol could result in good blood glucose control and prevent or retard development of diabetic complications such as diabetic nephropathy...
  73. ncbi Crystal structure of ABT-737 complexed with Bcl-xL: implications for selectivity of antagonists of the Bcl-2 family
    E F Lee
    Cell Death Differ 14:1711-3. 2007
  74. pmc 2-deoxyglucose-induced toxicity is regulated by Bcl-2 family members and is enhanced by antagonizing Bcl-2 in lymphoma cell lines
    O Zagorodna
    Department of Pathology, University of Iowa, Iowa City, IA 52242, USA
    Oncogene 31:2738-49. 2012
    ..Bcl-2 inhibition combined with 2DG may be an effective therapeutic strategy for lymphoma...
  75. ncbi Studies leading to potent, dual inhibitors of Bcl-2 and Bcl-xL
    Milan Bruncko
    Cancer Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064, USA
    J Med Chem 50:641-62. 2007
    ..Compound 2 demonstrated single agent efficacy against human follicular lymphoma cell lines that overexpress Bcl-2, and efficacy in a murine xenograft model of lymphoma when given both as a single agent and in combination with etoposide...
  76. ncbi Tipping the Noxa/Mcl-1 balance overcomes ABT-737 resistance in chronic lymphocytic leukemia
    Jacqueline M Tromp
    Departments of Hematology and Experimental Immunology, and Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Clin Cancer Res 18:487-98. 2012
    ..We aimed to define which antiapoptotic proteins determine resistance to ABT-737 in CLL and whether combination of known antileukemia drugs and ABT-737 was able to induce apoptosis of CD40-stimulated CLL cells...
  77. ncbi BH3 mimetics activate multiple pro-autophagic pathways
    S A Malik
    INSERM, U848, Institut Gustave Roussy, Villejuif, France
    Oncogene 30:3918-29. 2011
    ..These results point to unexpected and pleiotropic pro-autophagic effects of BH3 mimetics involving the modulation of multiple signalling pathways...
  78. pmc Biphenyl dioxygenases: functional versatilities and directed evolution
    Kensuke Furukawa
    Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Hakozaki, Fukuoka 812 8581, Japan
    J Bacteriol 186:5189-96. 2004
  79. ncbi The BH3 mimetic compound, ABT-737, synergizes with a range of cytotoxic chemotherapy agents in chronic lymphocytic leukemia
    K D Mason
    Divisions of Cancer and Haematology and Molecular Genetics of Cancer, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
    Leukemia 23:2034-41. 2009
    ..These data indicate that combination of ABT-737 with a second anti-leukemic agent would improve response rates and suggest a potential role for combination therapies that include BH3 mimetics for the treatment of this disease...
  80. ncbi Honokiol and magnolol induce Ca2+ mobilization in rat cortical neurons and human neuroblastoma SH-SY5Y cells
    Haifeng Zhai
    Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Yamashiro cho, 770 8514 Tokushima, Japan
    Eur J Pharmacol 474:199-204. 2003
    ..Thus, honokiol and magnolol may be involved in a new activation mechanism closely associated with intracellular Ca(2+) mobilization...
  81. ncbi The mechanism of honokiol-induced and magnolol-induced inhibition on muscle contraction and Ca2+ mobilization in rat uterus
    Yu Cheng Lu
    Department of Pharmacy, Buddhist Dalin Tzu Chi General Hospital, Chia Yi, Taiwan
    Naunyn Schmiedebergs Arch Pharmacol 368:262-9. 2003
    ..Honokiol and magnolol may be considered as putative Ca(2+) channel blockers and be of potential value in the treatment of gynecological dysfunctions associated with uterine muscular spasm and dysmenorrhea...
  82. ncbi Radical scavenging activity of black cumin (Nigella sativa L.), coriander (Coriandrum sativum L.), and niger (Guizotia abyssinica Cass.) crude seed oils and oil fractions
    Mohamed F Ramadan
    Institut fur Lebensmittelchemie, Technische Universitat Berlin, Gustav Meyer Allee 25, TIB 4 3 1, D 13355 Berlin, Germany
    J Agric Food Chem 51:6961-9. 2003
    ..As part of the effort to assess the potential of these seed oils, the information is also of importance in processing and utilizing the crude oils and their byproducts...
  83. ncbi The anti-inflammatory effect of honokiol on neutrophils: mechanisms in the inhibition of reactive oxygen species production
    Kuo Tong Liou
    Institute of Clinical Medicine, National Yang Ming University School of Medicine, Taipei, Taiwan
    Eur J Pharmacol 475:19-27. 2003
    ....
  84. ncbi Targeting the Bcl-2-regulated apoptosis pathway by BH3 mimetics: a breakthrough in anticancer therapy?
    V Labi
    Division of Developmental Immunology, Department of Biocenter, Innsbruck Medical University, Innsbruck, Austria
    Cell Death Differ 15:977-87. 2008
    ....
  85. ncbi A small-molecule inhibitor of Bcl-XL potentiates the activity of cytotoxic drugs in vitro and in vivo
    Alex R Shoemaker
    Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    Cancer Res 66:8731-9. 2006
    ..In tumors, the combination therapy also resulted in a significant increase in mitotic arrest followed by apoptosis relative to paclitaxel monotherapy...
  86. ncbi Antioxidative and hepatoprotective effects of magnolol on acetaminophen-induced liver damage in rats
    Yung Hsiang Chen
    Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan
    Arch Pharm Res 32:221-8. 2009
    ..Our study points out the potential interest of magnolol in the treatment of toxic ALF...
  87. ncbi Magnolol reduces myocardial ischemia/reperfusion injury via neutrophil inhibition in rats
    Y M Lee
    Department of Pharmacology, National Defense Medical Center, PO Box 90048-504, Nei-Hu, Taipei, Taiwan
    Eur J Pharmacol 422:159-67. 2001
    ..This pronounced cardioprotective activity of magnolol may be mediated by its antioxidant activity and by its capacity for neutrophil inhibition in myocardial ischemia/reperfusion...
  88. pmc Mcl1 downregulation sensitizes neuroblastoma to cytotoxic chemotherapy and small molecule Bcl2-family antagonists
    Brian J Lestini
    Division of Oncology, The Children s Hospital of Philadelphia, Philadelphia, PA 19104 4318, USA
    Cancer Biol Ther 8:1587-95. 2009
    ..Optimization of compounds with higher Mcl1 affinity, or combination with additional Mcl1 antagonists, may enhance the clinical utility of this approach...
  89. ncbi Irbesartan in patients with atrial fibrillation
    Salim Yusuf
    Population Health Research Institute, McMaster University, Hamilton, ON, Canada
    N Engl J Med 364:928-38. 2011
    ..The risk of cardiovascular events among patients with atrial fibrillation is high. We evaluated whether irbesartan, an angiotensin-receptor blocker, would reduce this risk...
  90. ncbi PPARgamma-activating angiotensin type-1 receptor blockers induce adiponectin
    Ronald Clasen
    Center for Cardiovascular Research, Institut fur Pharmakologie und Toxikologie, Charite Campus Mitte, Charite Universitatsmedizin Berlin, Berlin, Germany
    Hypertension 46:137-43. 2005
    ..ARB-induced adiponectin stimulation is likely to be mediated via PPARgamma activation involving a post-transcriptional mechanism...
  91. pmc Chronic administration of BMS309403 improves endothelial function in apolipoprotein E-deficient mice and in cultured human endothelial cells
    Mary Yk Lee
    Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
    Br J Pharmacol 162:1564-76. 2011
    ..Here, we investigate the contribution of A-FABP to the pathogenesis of endothelial dysfunction in the aorta of apolipoprotein E-deficient (ApoE(-/-) ) mice and in cultured human endothelial cells...
  92. ncbi Honokiol, a small molecular weight natural product, inhibits angiogenesis in vitro and tumor growth in vivo
    Xianhe Bai
    Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Biol Chem 278:35501-7. 2003
    ..Our preclinical data suggests that honokiol is a systemically available and non-toxic inhibitor of angiogenesis and should be further evaluated as a potential chemotherapeutic agent...
  93. ncbi Neuroprotective activity of honokiol and magnolol in cerebellar granule cell damage
    Yi Ruu Lin
    Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan
    Eur J Pharmacol 537:64-9. 2006
    ....
  94. ncbi Antioxidant activity of caffeic acid (3,4-dihydroxycinnamic acid)
    Ilhami Gulcin
    Faculty of Arts and Sciences, Department of Chemistry, Ataturk University, TR 25240 Erzurum, Turkey
    Toxicology 217:213-20. 2006
    ..In addition, caffeic acid is an effective ABTS(+) scavenging, DPPH scavenging, superoxide anion radical scavenging, total reducing power and metal chelating on ferrous ions activities...
  95. ncbi Bcl-2 family proteins are essential for platelet survival
    H Zhang
    Department of Cancer Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6101, USA
    Cell Death Differ 14:943-51. 2007
    ..Taken together, these data suggest that ABT-737 induces an apoptosis-like response in platelets that is distinct from platelet activation and results in enhanced clearance in vivo by the reticuloendothelial system...
  96. ncbi Anti-inflammatory activity of 4-methoxyhonokiol is a function of the inhibition of iNOS and COX-2 expression in RAW 264.7 macrophages via NF-kappaB, JNK and p38 MAPK inactivation
    Hong Yu Zhou
    Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151 742, South Korea
    Eur J Pharmacol 586:340-9. 2008
    ..7 macrophages...
  97. ncbi Killing cancer cells by flipping the Bcl-2/Bax switch
    Suzanne Cory
    The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia
    Cancer Cell 8:5-6. 2005
    ..Hence, this work validates Bcl-2-like proteins as important new targets in cancer therapy...
  98. ncbi The cathepsin K inhibitor odanacatib suppresses bone resorption in women with breast cancer and established bone metastases: results of a 4-week, double-blind, randomized, controlled trial
    Anders Bonde Jensen
    Aarhus University Hospital, Noerrebrogade 44, Aarhus C, Denmark
    Clin Breast Cancer 10:452-8. 2010
    ..This study assessed the pharmacokinetics, efficacy, and safety of odanacatib, a selective Cat K inhibitor, in reducing markers of bone resorption in women with breast cancer and MBD...
  99. pmc BH3 mimetic ABT-737 potentiates TRAIL-mediated apoptotic signaling by unsequestering Bim and Bak in human pancreatic cancer cells
    Shengbing Huang
    Miles and Shirley Fiterman Center for Digestive Diseases and Division of Oncology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Cancer Res 68:2944-51. 2008
    ..These findings suggest a novel strategy to enhance cross-talk between the extrinsic and intrinsic apoptotic pathways to improve therapeutic efficacy against pancreatic cancer...
  100. ncbi Evaluation of the antioxidant properties of litchi fruit phenolics in relation to pericarp browning prevention
    Xuewu Duan
    South China Botanical Garden, The Chinese Academy of Sciences, Guangzhou Leyiju 510650, PR China
    Molecules 12:759-71. 2007
    ..These results suggest that litchi pericarp tissue phenolics could be beneficial in scavenging free radicals, maintaining membrane integrity and, thereby inhibiting pericarp browning of litchi fruit...
  101. ncbi Angiotensin II type 2 receptor-mediated vasodilation in human coronary microarteries
    Wendy W Batenburg
    Department of Pharmacology, Erasmus MC, Rotterdam, The Netherlands
    Circulation 109:2296-301. 2004
    ..In contrast, AT2 receptor-mediated vasodilation could not be observed in large human coronary arteries. We studied Ang II-induced vasodilation of human coronary microarteries (HCMAs)...

Research Grants52

  1. Computational Design of Unnatural Amino Acid Dependent Metalloproteins
    Jeremy Mills; Fiscal Year: 2013
    ..impact with respect to bioremediation of persistent anthropomorphic toxins such as polychlorinated biphenyl compounds. The designed unnatural amino acid containing proteins will be produced in a bacterial expression system ..
  2. Small-molecule inhibitors of gp41-mediated fusion as HIV-1 topical microbicides
    Min Lu; Fiscal Year: 2010
    ..We will design and synthesize two sets of analogs of active triazinone and biphenyl compounds, characterize the equilibrium properties of interactions with the N-trimer coiled coil, and evaluate their ..
  3. Small-molecule inhibitors of gp41-mediated fusion as HIV-1 topical microbicides
    Min Lu; Fiscal Year: 2013
    ..We will design and synthesize two sets of analogs of active triazinone and biphenyl compounds, characterize the equilibrium properties of interactions with the N-trimer coiled coil, and evaluate their ..
  4. ALPHA 2 ADRENERGIC CONTROL IN IRRITABLE BOWEL SYNDROME
    Michael Camilleri; Fiscal Year: 2008
    ..Significance: This project will characterize pharmacogenetic mechanisms determining the response to clonidine through studies of candidate genes that control alpha2-adrenoreceptor function and norepinephrine transport in IBS. ..
  5. HIGH RESOLUTION ECHOCARDIOGRAPHY SYSTEM
    Michael Zile; Fiscal Year: 2001
    ..This will foster interdisciplinary investigation, support NIH-funded investigators and trainees, and enhance the competitiveness of MUSC investigators. ..
  6. "MENTORED PATIENT-ORIENTED RESEARCH CAREER DEVELOPMENT AWARD"
    Allon Friedman; Fiscal Year: 2009
    ..abstract_text> ..
  7. AN ENDOCANNABINOID MECHANISM FOR STRESS-INDUCED ANALGESIA
    ANDREA GRACE HOHMANN; Fiscal Year: 2010
    ..Furthermore, the results will provide essential information on the mechanisms responsible for endocannabinoid deactivation in the brain, which may facilitate the development of novel analgesic and anti- stress medicines. ..
  8. Cannabinoid Mechanisms in Human Gastrointestinal Motor and Sensory Functions
    MICHAEL L CAMILLERI; Fiscal Year: 2010
    ..These actions may be relevant to develop new treatments for IBS. The studies will also provide further understanding of the potential of medications like medical marijuana on stomach function that may be relevant to appetite control. ..
  9. ENDOCANNABINOID ANALGESIA: AN IN VIVO GENE TRANSFER - LIPIDOMICS APPROACH
    Andrea Hohmann; Fiscal Year: 2007
    ..Successful validation of our technological approach and hypotheses may facilitate development of endocannabinoid-based pharmacological and gene therapies for pain. [unreadable] [unreadable] [unreadable]..
  10. ALPHA-2 ADRENERGIC CONTROL OF COLONIC FUNCTION IN IBS
    Michael Camilleri; Fiscal Year: 2007
    ..abstract_text> ..
  11. Controlling the BCL-2 Pathway of Mitochondrial Apoptosis
    Anthony Letai; Fiscal Year: 2007
    ..Finally, we will use the mitochondrial, cellular and mouse assays developed above to test the efficacy and specificity of BH3 mimetics of both small molecule and peptidomimetic origin. [unreadable] [unreadable]..
  12. PERIPHERAL CANNABINOID MODULATION OF PAIN TRANSMISSION
    Andrea Hohmann; Fiscal Year: 2005
    ..abstract_text> ..
  13. MECHANISMS OF RISK TO DIABETIC NEPHROPATHY IN BLACKS
    Deborah Price; Fiscal Year: 2003
    ..Our goal in this study is to explore preliminary evidence that RAS activation and the combination with other polymorphic genes accounts for many Type II DM features involving renal risk and racial differences in risk. ..
  14. Oxidative Stress and Genetics of Prehypertension
    Shawna Nesbitt; Fiscal Year: 2004
    ..abstract_text> ..
  15. AASK Cohort Study
    George Bakris; Fiscal Year: 2007
    ..Such results might eventually lead to new strategies that delay or prevent ESRD. ..
  16. Designing HTA therapy for drug resistant malaria
    Christian Wolf; Fiscal Year: 2009
    ..Our long term goal is the identification of novel, inexpensive, efficacious therapy for treating drug resistant malaria. ..
  17. GENETICS OF HYPERTENSION AND ITS INTERMEDIATE PHENOTYPES
    Xiping Xu; Fiscal Year: 2001
    ..Thus, the genetic factors contributing to hypertension in this population may be less heterogeneous and more readily detected. ..
  18. Opposing Roles for MEK/ERK in Differentiation & Leukemia
    Daniel Johnson; Fiscal Year: 2009
    ....
  19. AUTONOMIC REGULATION OF AIRWAY SMOOTH MUSCLE TONE
    BRENDAN CANNING; Fiscal Year: 2001
    ..It is anticipated that this information will improve our understanding of the role of the autonomic innervation of the healthy and diseased lung. ..
  20. STUDIES IN MOLECULAR RECOGNITION
    Julius Rebek; Fiscal Year: 2010
    ..These cavitands could allow the identification of genes whose expression is influenced by trimethylation of particular lysines of the histones. ..
  21. Synthesis of Polyketides and Terpenes
    David A Evans; Fiscal Year: 2010
    ..As a consequence, organic synthesis is a critical discipline that continues to have an important impact on the fields of both medicine and biology. ..
  22. GENETICS OF AIRWAY RESPONSIVENESS AND LUNG FUNCTION
    Xiping Xu; Fiscal Year: 2001
    ....
  23. Dietary Omega-3 Fatty Acids and Sudden Cardiac Death
    GEORGE EDWARD BILLMAN; Fiscal Year: 2010
    ..This project will also determine the effectiveness of fish oil supplements in reducing sudden death due to a lethal abnormal heart rhythm after a heart attack. ..
  24. ALCOHOL AND MESOLIMBIC DOPAMINE PATHWAY
    QINGSHAN YAN; Fiscal Year: 2002
    ..This will elucidate the relative contribution of 5-HT2 receptors to the regulation of ethanol-induced DA release and help to explain the effects of 5-HT2 antagonists on alcohol consumption reported in the literature. ..
  25. Reflexes and Supraesophageal Consequences of Reflux Disease
    Brendan J Canning; Fiscal Year: 2010
    ..This research may also help identify novel therapeutic strategies for treating both GERD and chronic cough. ..
  26. Establishing the Precursors of Osteoporosis in Children
    Xiping Xu; Fiscal Year: 2010
    ....
  27. Role of TRPV1 in Airway Hypersensitivity Induced by Inflammation
    Lu Yuan Lee; Fiscal Year: 2010
    ..The results obtained from these studies should bring a new insight into the pathogenesis and therapeutic strategy for alleviating the airway hypersensitivity. ..
  28. ASYMMETRIC SYNTHESIS OF VANCOMYCIN ANTIBIOTICS
    David Evans; Fiscal Year: 2001
    ..During the course of this project we intend to confirm (correct) the absolute stereochemical assignments of the principal members of this family by total synthesis. ..
  29. ADRENAL NICOTINIC RECEPTORS AND CATECHOLAMINE SECRETION
    DENNIS MCKAY; Fiscal Year: 2001
    ..These studies should contribute significantly to our current knowledge of adrenal nAChRs and may also contribute to our basic understanding of neuronal nAChRs and their regulation. ..
  30. Chemosensitivity of Tachykinin-containing Lung Afferents
    Lu Yuan Lee; Fiscal Year: 2008
    ..The results obtained from this study should provide critical information for gaining new insights into the mechanisms underlying the airway hyperresponsiveness induced by cationic proteins. [unreadable] [unreadable]..
  31. ONCOGENE INDUCED LEUKEMOGENESIS IN TRANGENIC MICE
    Suzanne Cory; Fiscal Year: 2009
    ..abstract_text> ..
  32. POSTMENOPAUSAL HORMONAL REPLACEMENT THERAPY
    Wanpen Vongpatanasin; Fiscal Year: 2006
    ..The long-term goal of her work would be the discovery the most effective estrogen preparation that can prevent or treat hypertension in women after menopause. ..
  33. A NEW LEWIS ACID CATALYZED CLAISEN REARRANGEMENT
    DAVID MACMILLAN; Fiscal Year: 2004
    ..This new chemical tool should prove valuable for the rapid construction of erythronolide analogues; an important area of research for treatment of resistant bacterial strains. ..
  34. ASSEMBLIES OF SELF COMPLEMENTARY STRUCTURES
    Julius Rebek; Fiscal Year: 2005
    ..We also propose to synthesize new and larger capsules, especially those made up of many identical molecular subunits. ..
  35. Role of Cathepsin D in Chemotherapy Induced Cell Death
    Daniel Johnson; Fiscal Year: 2005
    ..Together, these studies will delineate the importance of cathepsin D in VP- 16-induced cell death, and define the mechanism of action of this protease. ..
  36. Organocatalysis: A Strategy for Asymmetric Synthesis
    DAVID MACMILLAN; Fiscal Year: 2005
    ..abstract_text> ..
  37. Effect of Daily Exercise on Cardiac Autonomic Regulation
    GEORGE BILLMAN; Fiscal Year: 2005
    ..Ventricular contractile responses to Beta1- and Beta2-adrenoceptor stimulation will be examined in vivo by echocardiography and in vitro by single cell fluorescence microscopy/video edge detection. ..
  38. ASYMMETRIC SYNTHESIS OF IONOPHORE/MACROLIDE ANTIBIOTICS
    David Evans; Fiscal Year: 2005
    ..Our goal has been to set in place all of the reactions necessary for the rapid assemblage of any polyketide target structure. ..
  39. PULMONARY C-NEURON HYPERSENSITIVITY:CELLULAR MECHANISMS
    Lu Yuan Lee; Fiscal Year: 2005
    ..This information may, therefore, help to develop new therapeutic strategies for alleviating the symptoms of bronchial hyperreactivity associated with airway mucosal inflammation. ..
  40. MECHANISMS IN THE REGULATION OF APOPTOSIS
    Jerry Adams; Fiscal Year: 2006
    ..Justification: As the proposal addresses central issues about the regulation of apoptosis, builds onproductive research, and exploits novel findings, it should significantly advance the molecular dissection of apoptosis. ..
  41. Inova 500 MHz Nuclear Magnetic Resonance System
    DAVID MACMILLAN; Fiscal Year: 2004
    ..The new 500 MHz instrument will be housed in contiguous space with the current Division NMR instruments. ..
  42. Neural Mechanism of Thiazide-Induced Insulin Resistance
    Wanpen Vongpatanasin; Fiscal Year: 2008
    ....
  43. RNAi-medicated inhibition of BDNF expression and alcohol-drinking behavior
    QINGSHAN YAN; Fiscal Year: 2008
    ..abstract_text> ..
  44. KININS AS MEDIATORS OF HUMAN REACTIONS
    BRENDAN CANNING; Fiscal Year: 2003
    ..These rigorous studies will not only clarify the role of BK in airway diseases, but will also have broader relevance by providing new and important insights into how neural function is altered in asthma and rhinitis. ..
  45. ORGANOPHOSPHATE PESTICIDES AND HUMAN REPRODUCTIVE HEALTH
    Xiping Xu; Fiscal Year: 2003
    ..S.; and (9) the population possesses unique characteristics for examining the proposed hypothesis, i.e., a stable workforce, a non-smoking group and excellent compliance rates. ..
  46. POSITIONAL CANDIDATE GENE APPROACHES IN ASTHMA GENE DISC
    Xiping Xu; Fiscal Year: 2006
    ..The findings from the proposed study may lead to improved strategies for prevention, diagnosis, and treatment of this disease. (End of Abstract.) ..
  47. GENETIC EPIDIMOLOGY OF OSTEOPOROSIS
    Xiping Xu; Fiscal Year: 2005
    ..OS (Osteoporosis in Men) studies. ..
  48. Synthesis of Macrolides, Steroids, Cyclopentanoids, etc.
    BARRY TROST; Fiscal Year: 2009
    ..These new synthetic methods apply to many structural types beyond those illustrated and constitutes a significant to gain access to complex molecular targets more easily. ..
  49. Identification and characterization of two novel cannabinoid receptors
    Alex Straiker; Fiscal Year: 2008
    ..Marijuana is a major drug of abuse, acting via cannabinoid receptors. Knowing the identity and function of all cannabinoid receptors is key to understanding how marijuana affects the body. [unreadable] [unreadable] [unreadable]..
  50. ANG II AND IGF-1 INTERACTION IN CARDIOVASCULAR TISSUE
    James Sowers; Fiscal Year: 2003
    ..Thus, the proposed investigation will explore the role of PI3-kinase in mediating the cardiovascular interactions of AngII/IGF-1 after both short-term in vitro Ang II exposure and longer-term in vivo Ang II tissue excess. ..