ALAN PAUL KOZIKOWSKI

Summary

Affiliation: University of Illinois at Chicago
Country: USA

Publications

  1. pmc Chemistry, biology, and QSAR studies of substituted biaryl hydroxamates and mercaptoacetamides as HDAC inhibitors-nanomolar-potency inhibitors of pancreatic cancer cell growth
    Alan P Kozikowski
    Drug Discovery Program, College of Pharmacy, University of Illinois at Chicago, 833 S Wood St, Chicago, Illinois 60612, USA
    ChemMedChem 3:487-501. 2008
  2. ncbi request reprint Use of the nitrile oxide cycloaddition (NOC) reaction for molecular probe generation: a new class of enzyme selective histone deacetylase inhibitors (HDACIs) showing picomolar activity at HDAC6
    Alan P Kozikowski
    Department of Medicinal Chemistry and Pharmacognosy, Drug Discovery Program, University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612, USA
    J Med Chem 51:4370-3. 2008
  3. ncbi request reprint Chemical medicine: novel 10-substituted cytisine derivatives with increased selectivity for alpha4beta2 nicotinic acetylcholine receptors
    Alan P Kozikowski
    Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612, USA
    ChemMedChem 2:1157-61. 2007
  4. pmc Searching for disease modifiers-PKC activation and HDAC inhibition - a dual drug approach to Alzheimer's disease that decreases Abeta production while blocking oxidative stress
    Alan P Kozikowski
    Drug Discovery Program, College of Pharmacy, University of Illinois at Chicago, 833 S Wood St, Chicago, IL 60612, USA
    ChemMedChem 4:1095-105. 2009
  5. doi request reprint Stereoselective HDAC inhibition from cysteine-derived zinc-binding groups
    Kyle V Butler
    Department of Medicinal Chemistry, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA
    ChemMedChem 4:1292-301. 2009
  6. ncbi request reprint Derivatives of 3-isoxazolecarboxylic acid esters: a potent and selective compound class against replicating and nonreplicating Mycobacterium tuberculosis
    Annamaria Lilienkampf
    Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA
    Curr Top Med Chem 12:729-34. 2012
  7. pmc Intracerebroventricular administration of N-acetylaspartylglutamate (NAAG) peptidase inhibitors is analgesic in inflammatory pain
    Tatsuo Yamamoto
    Department of Biology, Georgetown University, Washington, DC 20057, USA
    Mol Pain 4:31. 2008
  8. ncbi request reprint Structural remodeling of cocaine: design and synthesis of trisubstituted cyclopropanes as selective serotonin reuptake inhibitors
    Alan P Kozikowski
    Drug Discovery Program, Department of Neurology, Georgetown University Medical Center, 3900 Reservoir Road, NW, Washington, DC 20007, USA
    ChemMedChem 1:58-65. 2006
  9. ncbi request reprint Synthesis of urea-based inhibitors as active site probes of glutamate carboxypeptidase II: efficacy as analgesic agents
    Alan P Kozikowski
    Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, 539 College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612, USA
    J Med Chem 47:1729-38. 2004
  10. ncbi request reprint Structure-based design leads to the identification of lithium mimetics that block mania-like effects in rodents. possible new GSK-3beta therapies for bipolar disorders
    Alan P Kozikowski
    Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA
    J Am Chem Soc 129:8328-32. 2007

Collaborators

Detail Information

Publications68

  1. pmc Chemistry, biology, and QSAR studies of substituted biaryl hydroxamates and mercaptoacetamides as HDAC inhibitors-nanomolar-potency inhibitors of pancreatic cancer cell growth
    Alan P Kozikowski
    Drug Discovery Program, College of Pharmacy, University of Illinois at Chicago, 833 S Wood St, Chicago, Illinois 60612, USA
    ChemMedChem 3:487-501. 2008
    ..Of particular interest is the selectivity of the mercaptoacetamides for HDAC6...
  2. ncbi request reprint Use of the nitrile oxide cycloaddition (NOC) reaction for molecular probe generation: a new class of enzyme selective histone deacetylase inhibitors (HDACIs) showing picomolar activity at HDAC6
    Alan P Kozikowski
    Department of Medicinal Chemistry and Pharmacognosy, Drug Discovery Program, University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612, USA
    J Med Chem 51:4370-3. 2008
    ..Some of the compounds were examined for their ability to block pancreatic cancer cell growth and found to be about 10-fold more potent than SAHA. This research provides valuable, new molecular probes for use in exploring HDAC biology...
  3. ncbi request reprint Chemical medicine: novel 10-substituted cytisine derivatives with increased selectivity for alpha4beta2 nicotinic acetylcholine receptors
    Alan P Kozikowski
    Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612, USA
    ChemMedChem 2:1157-61. 2007
  4. pmc Searching for disease modifiers-PKC activation and HDAC inhibition - a dual drug approach to Alzheimer's disease that decreases Abeta production while blocking oxidative stress
    Alan P Kozikowski
    Drug Discovery Program, College of Pharmacy, University of Illinois at Chicago, 833 S Wood St, Chicago, IL 60612, USA
    ChemMedChem 4:1095-105. 2009
    ..These findings may offer a new approach to therapies that exhibit disease-modifying effects, as opposed to symptomatic relief, in the treatment of AD...
  5. doi request reprint Stereoselective HDAC inhibition from cysteine-derived zinc-binding groups
    Kyle V Butler
    Department of Medicinal Chemistry, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA
    ChemMedChem 4:1292-301. 2009
    ..Molecular modeling was employed to investigate the differences in inhibitory activity between the HDAC inhibitors generated from the two enantiomeric forms of cysteine...
  6. ncbi request reprint Derivatives of 3-isoxazolecarboxylic acid esters: a potent and selective compound class against replicating and nonreplicating Mycobacterium tuberculosis
    Annamaria Lilienkampf
    Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA
    Curr Top Med Chem 12:729-34. 2012
    ..The foregoing facts make derivatives of 3- isoxazolecarboxylic acid esters a promising anti-TB chemotype, and as such present attractive lead compounds for TB drug development...
  7. pmc Intracerebroventricular administration of N-acetylaspartylglutamate (NAAG) peptidase inhibitors is analgesic in inflammatory pain
    Tatsuo Yamamoto
    Department of Biology, Georgetown University, Washington, DC 20057, USA
    Mol Pain 4:31. 2008
    ..Consistent with NAAG's activation of group II metabotropic glutamate receptors, this analgesia is blocked by a group II antagonist...
  8. ncbi request reprint Structural remodeling of cocaine: design and synthesis of trisubstituted cyclopropanes as selective serotonin reuptake inhibitors
    Alan P Kozikowski
    Drug Discovery Program, Department of Neurology, Georgetown University Medical Center, 3900 Reservoir Road, NW, Washington, DC 20007, USA
    ChemMedChem 1:58-65. 2006
  9. ncbi request reprint Synthesis of urea-based inhibitors as active site probes of glutamate carboxypeptidase II: efficacy as analgesic agents
    Alan P Kozikowski
    Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, 539 College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612, USA
    J Med Chem 47:1729-38. 2004
    ..These urea-based inhibitors of GCPII thus offer a novel approach to pain management...
  10. ncbi request reprint Structure-based design leads to the identification of lithium mimetics that block mania-like effects in rodents. possible new GSK-3beta therapies for bipolar disorders
    Alan P Kozikowski
    Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA
    J Am Chem Soc 129:8328-32. 2007
    ..Selective brain penetrable GSK-3 ligands like those described herein become valuable research tools in better defining the role of this multifaceted kinase in both physiological and pathophysiological events...
  11. ncbi request reprint Functional differences in epigenetic modulators-superiority of mercaptoacetamide-based histone deacetylase inhibitors relative to hydroxamates in cortical neuron neuroprotection studies
    Alan P Kozikowski
    Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612, USA
    J Med Chem 50:3054-61. 2007
    ....
  12. ncbi request reprint Acetylenic pyridines for use in PET imaging of nicotinic receptors
    Alan P Kozikowski
    Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612, USA
    ChemMedChem 2:54-7. 2007
  13. ncbi request reprint Highly potent and specific GSK-3beta inhibitors that block tau phosphorylation and decrease alpha-synuclein protein expression in a cellular model of Parkinson's disease
    Alan P Kozikowski
    Drug Discovery Program, College of Pharmacy, University of Illinois at Chicago, 833 S Wood St, Chicago, Illinois 60612, USA
    ChemMedChem 1:256-66. 2006
    ....
  14. doi request reprint On the path from chemistry to neuroscience: early explorations in chemical medicine under the mentorship of Dr. Erminio Costa, a neuroscientist with a big brain and a bigger heart
    Alan P Kozikowski
    Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL, United States
    Pharmacol Res 64:327-9. 2011
    ....
  15. pmc Identification of a glycogen synthase kinase-3β inhibitor that attenuates hyperactivity in CLOCK mutant mice
    Alan P Kozikowski
    Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612, USA
    ChemMedChem 6:1593-602. 2011
    ....
  16. pmc Chemistry and pharmacology of nicotinic ligands based on 6-[5-(azetidin-2-ylmethoxy)pyridin-3-yl]hex-5-yn-1-ol (AMOP-H-OH) for possible use in depression
    Alan P Kozikowski
    Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, USA
    ChemMedChem 4:1279-91. 2009
    ..Inactivation of nAChRs may be a common neurochemical endpoint for nicotine dependence, its treatment, and some of its manifestations, including relief from depression...
  17. pmc Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A
    Kyle V Butler
    Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 South Wood, Chicago, Illinois 60612, USA
    J Am Chem Soc 132:10842-6. 2010
    ....
  18. ncbi request reprint SAR studies of piperidine-based analogues of cocaine. 4. Effect of N-modification and ester replacement
    Pavel A Petukhov
    Drug Discovery Program, Department of Neurology, Georgetown University Medical Center, 3900 Reservoir Road, N W, Washington, D C 20007, USA
    J Med Chem 45:3161-70. 2002
    ....
  19. ncbi request reprint Further studies on conformationally constrained tricyclic tropane analogues and their uptake inhibition at monoamine transporter sites: synthesis of (Z)-9-(substituted arylmethylene)-7-azatricyclo[4.3.1.0(3,7)]decanes as a novel class of serotonin transpo
    Ao Zhang
    Drug Discovery Program, Department of Neurology, Georgetown University Medical Center, 3900 Reservoir Road Northwest, Washington, DC 20007 2197, USA
    J Med Chem 45:1930-41. 2002
    ..06 nM and has essentially no activity at the DAT or NET. The present results have important implications for drug addiction as well as a number of psychiatric diseases...
  20. ncbi request reprint Thiophene derivatives: a new series of potent norepinephrine and serotonin reuptake inhibitors
    Ao Zhang
    Drug Discovery Program, Department of Neurology, Georgetown University Medical Center, 3900 Reservoir Road, NW, Washington, DC 20007 2197, USA
    Bioorg Med Chem Lett 12:993-5. 2002
    ..Compound 5b is a NET-selective inhibitor, 5c is a mixed NET- and SERT-selective inhibitor, while 11 is a SERT-selective inhibitor...
  21. ncbi request reprint 2,3-Disubstituted quinuclidines as a novel class of dopamine transporter inhibitors
    Sukumar Sakamuri
    Department of Neurology, Georgetown University Medical Center, 3900 Reservoir Rd, Washington, DC 20007, USA
    Bioorg Med Chem 11:1123-36. 2003
    ..Thus, 34 may serve as a novel lead compound in the ultimate development of therapeutic entities for cocaine abuse and/or addiction...
  22. doi request reprint Studies of benzamide- and thiol-based histone deacetylase inhibitors in models of oxidative-stress-induced neuronal death: identification of some HDAC3-selective inhibitors
    Yufeng Chen
    Drug Discovery Program, College of Pharmacy, University of Illinois at Chicago, 833 S Wood St, Chicago, IL 60612, USA
    ChemMedChem 4:842-52. 2009
    ....
  23. ncbi request reprint CoMFA study of piperidine analogues of cocaine at the dopamine transporter: exploring the binding mode of the 3 alpha-substituent of the piperidine ring using pharmacophore-based flexible alignment
    Hongbin Yuan
    Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, USA
    J Med Chem 47:6137-43. 2004
    ....
  24. pmc Synthesis and biological evaluation of triazol-4-ylphenyl-bearing histone deacetylase inhibitors as anticancer agents
    Rong He
    Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612, USA
    J Med Chem 53:1347-56. 2010
    ..Taken together, these data further support the value of the triazol-4-ylphenyl bearing hydroxamates in identifying potential pancreatic cancer therapies...
  25. pmc Chemistry and pharmacological characterization of novel nitrogen analogues of AMOP-H-OH (Sazetidine-A, 6-[5-(azetidin-2-ylmethoxy)pyridin-3-yl]hex-5-yn-1-ol) as α4β2-nicotinic acetylcholine receptor-selective partial agonists
    Jianhua Liu
    Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612, USA
    J Med Chem 53:6973-85. 2010
    ....
  26. ncbi request reprint Biaryl analogues of conformationally constrained tricyclic tropanes as potent and selective norepinephrine reuptake inhibitors: synthesis and evaluation of their uptake inhibition at monoamine transporter sites
    Jia Zhou
    Drug Discovery Program, Department of Neurology, Georgetown University Medical Center, 3970 Reservoir Road, NW, Washington, DC 20057 2197, USA
    J Med Chem 46:1997-2007. 2003
    ..Some of the compounds in this series may also be valuable in sorting out the contribution of the individual transporters to cocaine's reinforcing properties...
  27. ncbi request reprint New bivalent PKC ligands linked by a carbon spacer: enhancement in binding affinity
    Jayalakshmi Sridhar
    Drug Discovery Program, Department of Neurology, Georgetown University Medical Center, 3970, Reservoir Road, NW, Washington, D C 20057 2197, USA
    J Med Chem 46:4196-204. 2003
    ..The high binding affinity of compounds 2d-g to PKCs gives us the impetus to design additional molecules that would retain this enhanced activity and would also show selectivity for the PKC isoforms...
  28. pmc From a natural product lead to the identification of potent and selective benzofuran-3-yl-(indol-3-yl)maleimides as glycogen synthase kinase 3beta inhibitors that suppress proliferation and survival of pancreatic cancer cells
    Irina N Gaisina
    Department of Medicinal Chemistry and Pharmacognosy, Drug Discovery Program, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, USA
    J Med Chem 52:1853-63. 2009
    ..The present data suggest a possible role for GSK-3beta inhibitors in cancer therapy, in addition to their more prominent applications in CNS disorders...
  29. pmc Molecular modeling, synthesis, and activity studies of novel biaryl and fused-ring BACE1 inhibitors
    Srinivas Reddy Chirapu
    Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA
    Bioorg Med Chem Lett 19:264-74. 2009
    ..Ligand 5b reduced 65% of Abeta40 production in N2a cells stably transfected with Swedish human APP...
  30. ncbi request reprint Synthesis and pharmacological characterization of bivalent ligands of epibatidine at neuronal nicotinic acetylcholine receptors
    Zhi Liang Wei
    Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 S Wood Street, Chicago, IL 60612, USA
    Bioorg Med Chem Lett 14:1855-8. 2004
    ..In contrast to epibatidine, these bivalent ligands are weak partial agonists at the alpha3beta4 nAChR as shown by functional assays...
  31. ncbi request reprint New amide-bearing benzolactam-based protein kinase C modulators induce enhanced secretion of the amyloid precursor protein metabolite sAPPalpha
    Alan P Kozikowski
    Drug Discovery Program, Department of Neurology, Georgetown University Medical Center, 3970 Reservoir Road, NW, Washington, D C 20007 2197, USA
    J Med Chem 46:364-73. 2003
    ..Compound 5e thus becomes a viable candidate compound in the search for Alzheimer's therapeutics capable of modulating amyloid processing...
  32. ncbi request reprint Synthesis and modeling study of (2S,5R,6R)- and (2S,5R,6S)-6-hydroxy- 8-(1-decynyl)-benzolactam-V8 as protein kinase C modulators
    Zhi Liang Wei
    Drug Discovery Program, Department of Neurology, Georgetown University Medical Center, 3900 Reservoir Road, NW, Washington, DC 20007, USA
    Org Lett 4:2169-72. 2002
    ..Biological assays reveal the (6R)-ligand to be 20-fold more potent than its (6S)-counterpart in binding to PKC alpha...
  33. ncbi request reprint Chemistry and biology of mercaptoacetamides as novel histone deacetylase inhibitors
    Bin Chen
    Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612, USA
    Bioorg Med Chem Lett 15:1389-92. 2005
    ..Their ability to inhibit HDAC activity and their effects on cancer cell growth were investigated. Some compounds exhibit better HDAC inhibitory activity than SAHA...
  34. pmc Synthesis and pharmacological evaluation of novel 9- and 10-substituted cytisine derivatives. Nicotinic ligands of enhanced subtype selectivity
    Sheela K Chellappan
    Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Illinois 60612, USA
    J Med Chem 49:2673-6. 2006
    ..The 9-vinyl derivative was found to have a very similar agonist activity profile to that of cytisine...
  35. doi request reprint A series of potent and selective, triazolylphenyl-based histone deacetylases inhibitors with activity against pancreatic cancer cells and Plasmodium falciparum
    Yufeng Chen
    Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612, USA
    J Med Chem 51:3437-48. 2008
    ..Lastly, these new HDACIs were studied for both their anticancer and antimalarial activity, which serve to validate the superior activity of the HDACI 10c...
  36. ncbi request reprint Synthesis, molecular modeling, and biological studies of novel piperidine-based analogues of cocaine: evidence of unfavorable interactions proximal to the 3alpha-position of the piperidine ring
    Pavel A Petukhov
    Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy MC 781, University of Illinois at Chicago, 833 S Wood Street 539, Chicago, IL 60612, USA
    J Med Chem 47:3009-18. 2004
    ....
  37. pmc Design and synthesis of aryl ether inhibitors of the Bacillus anthracis enoyl-ACP reductase
    Suresh K Tipparaju
    Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 S Wood St, Chicago, IL 60612, USA
    ChemMedChem 3:1250-68. 2008
    ..aureus. X-ray crystal structures of BaENR in complex with triclosan and two other compounds help explain the improved efficacy of the new compounds and suggest future rounds of optimization that might be used to improve their potency...
  38. ncbi request reprint Novel pyridyl ring C5 substituted analogues of epibatidine and 3-(1-methyl-2(S)-pyrrolidinylmethoxy)pyridine (A-84543) as highly selective agents for neuronal nicotinic acetylcholine receptors containing beta2 subunits
    Zhi Liang Wei
    Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612, USA
    J Med Chem 48:1721-4. 2005
    ..Our data indicate that the extracellular domains of the nAChRs are sufficiently different to allow for the design of novel ligands with high affinity and selectivity for the nAChR subtypes...
  39. ncbi request reprint Synthesis and pharmacological evaluation of 8- and 9-substituted benzolactam-v8 derivatives as potent ligands for protein kinase C, a therapeutic target for Alzheimer's disease
    Ulrich R Mach
    Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 S Wood St, Chicago, Illinois 60612, USA
    ChemMedChem 1:307-14. 2006
    ..An interesting decrease in binding affinity was found for the 9-thienyl analogue 13, suggesting adverse electronic interactions of the sulfur atom with PKC or parts of the cellular membrane...
  40. ncbi request reprint Further structure-activity relationship studies of piperidine-based monoamine transporter inhibitors: effects of piperidine ring stereochemistry on potency. Identification of norepinephrine transporter selective ligands and broad-spectrum transporter inhi
    Rong He
    Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy M C781, University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612 7230, USA
    J Med Chem 48:7970-9. 2005
    ....
  41. ncbi request reprint Sazetidine-A, a novel ligand that desensitizes alpha4beta2 nicotinic acetylcholine receptors without activating them
    Yingxian Xiao
    Department of Pharmacology, Georgetown University School of Medicine, Washington, DC 20057, USA
    Mol Pharmacol 70:1454-60. 2006
    ....
  42. doi request reprint Creating zinc monkey wrenches in the treatment of epigenetic disorders
    Jay Hans Kalin
    University of Illinois at Chicago, Department of Medicinal Chemistry, 833 South Wood Street, Chicago, IL 60612, USA
    Curr Opin Chem Biol 13:263-71. 2009
    ..Based on the diverse utility and wide range of mechanistic actions observed with this class of drugs, the future development of better drug combination therapies and more selective HDACIs is warranted...
  43. pmc Selective 5-hydroxytryptamine 2C receptor agonists derived from the lead compound tranylcypromine: identification of drugs with antidepressant-like action
    Sung Jin Cho
    Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612 7230, USA
    J Med Chem 52:1885-902. 2009
    ..8 nM at the 2A, 2B, and 2C subtypes, respectively). In animal studies, compound 37 (10-60 mg/kg) decreased immobility time in the mouse forced swim test...
  44. ncbi request reprint Structural basis of RasGRP binding to high-affinity PKC ligands
    Suo Bao Rong
    Drug Discovery Program, Department of Neurology, Georgetown University Medical Center, 3970 Reservoir Road, Washington, D C 20007, USA
    J Med Chem 45:853-60. 2002
    ..Taken together, our experimental and modeling studies provide us with a better understanding of the structural basis of the binding of PKC ligands to the novel phorbol ester receptor RasGRP...
  45. doi request reprint Structure-activity relationships of compounds targeting mycobacterium tuberculosis 1-deoxy-D-xylulose 5-phosphate synthase
    Jialin Mao
    Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612, USA
    Bioorg Med Chem Lett 18:5320-3. 2008
    ..Ultimately we found that 2-methyl-3-(4-fluorophenyl)-5-(4-methoxy-phenyl)-4H-pyrazolo[1,5-a]pyrimidin-7-one, although still weak, was able to inhibit M. tuberculosis DXS with an IC(50) of 10.6 microM...
  46. ncbi request reprint Synthesis, nicotinic acetylcholine receptor binding affinities, and molecular modeling of constrained epibatidine analogues
    Zhi Liang Wei
    Drug Discovery Program, Department of Neurology, Georgetown University Medical Center, 3900 Reservoir Road, NW, Washington, DC 20057, USA
    J Med Chem 46:921-4. 2003
    ..Modeling studies suggest that the spatial distribution of the ligand's atoms around the pharmacophore elements may control their nAChR subtype selectivity...
  47. ncbi request reprint Molecular modeling of the interactions of glutamate carboxypeptidase II with its potent NAAG-based inhibitors
    Suo Bao Rong
    Department of Neurology, Department of Pharmacology, Georgetown University Medical Center, 3970 Reservoir Road, Washington, DC 20007, USA
    J Med Chem 45:4140-52. 2002
    ..On the basis of the predicted interaction mode, our structure-based design has led to a series of highly potent GCPII inhibitors...
  48. pmc Design and synthesis of 2-pyridones as novel inhibitors of the Bacillus anthracis enoyl-ACP reductase
    Suresh K Tipparaju
    Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 S Wood Street, Chicago, IL 60612, USA
    Bioorg Med Chem Lett 18:3565-9. 2008
    ..A number of novel 2-pyridone derivatives were synthesized and shown to be potent inhibitors of BaENR...
  49. pmc Identification and development of novel inhibitors of Toxoplasma gondii enoyl reductase
    Suresh K Tipparaju
    Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois, USA
    J Med Chem 53:6287-300. 2010
    ..This provides a paradigm, conceptual foundation, reagents, and lead compounds for future rational development and discovery of improved inhibitors of T. gondii...
  50. ncbi request reprint Chemical origins of isoform selectivity in histone deacetylase inhibitors
    Kyle V Butler
    University of Illinois at Chicago, Department of Medicinal Chemistry, Chicago, IL 60612, USA
    Curr Pharm Des 14:505-28. 2008
    ..This review will focus on the applications of selective HDAC inhibitors, inhibitors reported to show selectivity, and the relationship between inhibitor structure and selectivity...
  51. ncbi request reprint NAAG peptidase inhibition reduces locomotor activity and some stereotypes in the PCP model of schizophrenia via group II mGluR
    Rafal T Olszewski
    Department of Biology, Georgetown University, Washington, DC, USA
    J Neurochem 89:876-85. 2004
    ..These data support the view that NAAG peptidase inhibitors may represent a new therapeutic approach to some of the components of schizophrenia that are modeled by PCP...
  52. ncbi request reprint Design, synthesis, and pharmacological evaluation of mefloquine-based ligands as novel antituberculosis agents
    Jialin Mao
    Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612, USA
    ChemMedChem 2:1624-30. 2007
    ..The clear structure-activity relationships (SARs) derived from this study should facilitate our ultimate goal of identifying improved anti-TB agents...
  53. ncbi request reprint Synthesis and structure-activity relationships of 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine analogues as potent, noncompetitive metabotropic glutamate receptor subtype 5 antagonists; search for cocaine medications
    Yasuyoshi Iso
    Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612, USA
    J Med Chem 49:1080-100. 2006
    ..Two compounds 19 and 59 exhibited functional activity as mGluR5 antagonists that are 490 and 230 times, respectively, better than that of MTEP...
  54. pmc Isoxazole moiety in the linker region of HDAC inhibitors adjacent to the Zn-chelating group: effects on HDAC biology and antiproliferative activity
    Subhasish Tapadar
    Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL 60612, USA
    Bioorg Med Chem Lett 19:3023-6. 2009
    ..Some of these compounds showed nanomolar activity in the HDAC isoform inhibitory assay and exhibited micro molar inhibitory activity against five pancreatic cancer cell lines...
  55. ncbi request reprint Synthesis and biological activity of novel neuroprotective diketopiperazines
    K R C Prakash
    Drug Discovery Program, Department of Neurology, Georgetown University Medical Center, 3900 Reservoir Road, N W, Washington, DC 20007 2197, USA
    Bioorg Med Chem 10:3043-8. 2002
    ..The neuroprotective profile of these compounds suggests that they may be useful as treatments for neuronal degeneration in vivo, potentially through several different mechanisms...
  56. doi request reprint Searching for new cures for tuberculosis: design, synthesis, and biological evaluation of 2-methylbenzothiazoles
    Qingqing Huang
    Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois 60612, USA
    J Med Chem 52:6757-67. 2009
    ..These studies thus suggest that certain 2-methylbenzothiazole based compounds may serve as promising lead scaffolds for further elaboration as anti-TB drugs and as possible antimalaria drugs...
  57. ncbi request reprint Design and synthesis of a potent and selective peptidomimetic inhibitor of caspase-3
    Nicola Micale
    Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 South Wood Street, Illinois 60612, USA
    J Med Chem 47:6455-8. 2004
    ....
  58. ncbi request reprint Novel HDAC inhibitors with radiosensitizing properties
    Mira Jung
    Department of Radiation Medicine, Georgetown University Medical Center, Washington, DC 20057, USA
    Radiat Res 163:488-93. 2005
    ..The data support the further investigation of these HDAC inhibitors for use as sensitizing agents with potential for clinical application...
  59. ncbi request reprint Functionalization of the alicyclic skeleton of epibatidine: synthesis and nicotinic acetylcholine receptor binding affinities of epibatidine analogues
    Zhi Liang Wei
    Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 S Wood Street, Chicago, Illinois 60612 7231, USA
    Org Biomol Chem 1:3878-81. 2003
    ..2.1]heptan-3-one (12) on silica gel was developed and used as the key step to synthesize functionalized analogues of epibatidine which were evaluated for their nicotine receptor subtype selectivity in binding studies...
  60. pmc The amino terminus of tau inhibits kinesin-dependent axonal transport: implications for filament toxicity
    Nichole E LaPointe
    Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
    J Neurosci Res 87:440-51. 2009
    ..Our results suggest that pathological tau aggregation contributes to neurodegeneration by altering a regulatory pathway for FAT...
  61. ncbi request reprint Mixed cocaine agonist/antagonist properties of (+)-methyl 4beta-(4-chlorophenyl)-1-methylpiperidine-3alpha-carboxylate, a piperidine-based analog of cocaine
    Alan P Kozikowski
    Drug Discovery Program, Departments of Neurology, Georgetown University Medical Center, Washington, DC, USA
    J Pharmacol Exp Ther 305:143-50. 2003
    ..These properties of (+)-CPCA suggest that it may have utility in the treatment of cocaine craving and dependence...
  62. ncbi request reprint Neuroprotective and nootropic actions of a novel cyclized dipeptide after controlled cortical impact injury in mice
    Alan I Faden
    Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road NW, Room EP 12, Washington, DC 20057, USA
    J Cereb Blood Flow Metab 23:355-63. 2003
    ..In addition, they show that 35b has a relatively wide therapeutic window and improves cognitive function after both acute and chronic injury...
  63. ncbi request reprint Novel diketopiperazine enhances motor and cognitive recovery after traumatic brain injury in rats and shows neuroprotection in vitro and in vivo
    Alan I Faden
    Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road NW, Room EP 12, Washington, DC 20057, USA
    J Cereb Blood Flow Metab 23:342-54. 2003
    ..Thus, 35b shows none of the typical physiologic actions associated with TRH, but possesses neuroprotective actions in vivo and in vitro, and appears to attenuate both necrotic and apoptotic cell death...
  64. ncbi request reprint Antinociceptive pharmacology of N-(4-chlorobenzyl)-N'-(4-hydroxy-3-iodo-5-methoxybenzyl) thiourea, a high-affinity competitive antagonist of the transient receptor potential vanilloid 1 receptor
    Lei Tang
    Department of Biopharmaceutical Sciences, and Cancer Center, University of Illinois, 833 South Woods St, Chicago, IL 60612, USA
    J Pharmacol Exp Ther 321:791-8. 2007
    ..Taken together, these data demonstrate that IBTU acts as a TRPV1 antagonist in vivo, and they suggest that it may be of therapeutic use for the treatment of pain...
  65. ncbi request reprint Synthesis of more potent analogues of the acetylcholinesterase inhibitor, huperzine B
    V Rajendran
    Drug Discovery Program, Department of Neurology, Georgetown University Medical Center, 3900 Reservoir Road NW, Washington DC 20007 2197, USA
    Bioorg Med Chem Lett 12:1521-3. 2002
    ..The synthesis and acetylcholinesterase inhibition activity of analogues of huperzine B are reported. These new racemic analogues show a better AChE inhibitory activity than the natural product huperzine B...
  66. pmc Use of molecular modeling, docking, and 3D-QSAR studies for the determination of the binding mode of benzofuran-3-yl-(indol-3-yl)maleimides as GSK-3beta inhibitors
    Ki Hwan Kim
    Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 60612, USA
    J Mol Model 15:1463-79. 2009
    ..The 3D-QSAR models were used for the estimation of the inhibitory potency of two additional compounds...
  67. ncbi request reprint Novel PI analogues selectively block activation of the pro-survival serine/threonine kinase Akt
    Alan P Kozikowski
    Drug Discovery Program, Department of Neurology, Georgetown University, 3900 Reservoir Road, NW, Washington, DC 20007, USA
    J Am Chem Soc 125:1144-5. 2003
    ..Specific inhibition of Akt by these compounds validates ligand design targeted to the PH domains of crucial signaling proteins, thus providing a unique class of possible cancer therapeutics...
  68. ncbi request reprint Stereochemistry at the forefront in the design and discovery of novel anti-tuberculosis agents
    Qingqing Huang
    Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois 60612, USA
    Curr Top Med Chem 11:810-8. 2011
    ..This review will focus on the reported chiral anti-TB agents together with the clinical importance of their chirality and stereochemistry...

Research Grants40

  1. Chemistry and Pharmacology of a New Nicotine Ligands
    Alan Kozikowski; Fiscal Year: 2007
    ..Functional activity will be evaluated using established 86RbC1 efflux assays and/or whole cell patch clamp measurements. ..
  2. DESIGN OF LIGANDS SELECTIVE FOR THE DAG SUPERFAMILY
    Alan Kozikowski; Fiscal Year: 2002
    ..To assess the effect of alterations in the ligand's hydrophobic side chain on its tumor promoting activity, studies of skin hyperplasia will be conducted. ..
  3. Chemistry and Biology of 5-HT2C Receptor Ligands for Drug Abuse
    Alan Kozikowski; Fiscal Year: 2009
    ....
  4. PKC Modulators for the Treatment of Alzheimer's disease
    Alan Kozikowski; Fiscal Year: 2006
    ..For the best compounds from Aim 2, perform studies in triple transgenic mice to ascertain effects on Abeta and sAPPalpha levels and plaque formation in vivo. ..
  5. Chemistry and Pharmacology of a New Nicotine Ligands
    Alan Kozikowski; Fiscal Year: 2006
    ..Functional activity will be evaluated using established 86RbC1 efflux assays and/or whole cell patch clamp measurements. ..
  6. PKC Modulators for the Treatment of Alzheimer's disease
    Alan Kozikowski; Fiscal Year: 2005
    ..For the best compounds from Aim 2, perform studies in triple transgenic mice to ascertain effects on Abeta and sAPPalpha levels and plaque formation in vivo. ..
  7. Chemistry and Pharmacology of a New Nicotine Ligands
    Alan Kozikowski; Fiscal Year: 2005
    ..Functional activity will be evaluated using established 86RbC1 efflux assays and/or whole cell patch clamp measurements. ..
  8. CHEMICAL AND PHARMACOLOGICAL STUDIES OF COCAINE ANALOGS
    Alan Kozikowski; Fiscal Year: 2003
    ....
  9. Chemistry and Pharmacology of a New Nicotine Ligands
    Alan Kozikowski; Fiscal Year: 2004
    ..Functional activity will be evaluated using established 86RbC1 efflux assays and/or whole cell patch clamp measurements. ..
  10. CHEMICAL AND PHARMACOLOGICAL STUDIES OF COCAINE ANALOGS
    Alan Kozikowski; Fiscal Year: 2004
    ....
  11. Molecular Interventions for Bipolar Disorder
    Alan Kozikowski; Fiscal Year: 2007
    ..using their patented SmartCube technology. ..
  12. PKC Modulators for the Treatment of Alzheimer's disease
    Alan Kozikowski; Fiscal Year: 2007
    ..For the best compounds from Aim 2, perform studies in triple transgenic mice to ascertain effects on Abeta and sAPPalpha levels and plaque formation in vivo. ..
  13. Molecular Interventions for Bipolar Disorder
    ALAN PAUL KOZIKOWSKI; Fiscal Year: 2010
    ..using their patented SmartCube technology. ..
  14. Molecular Interventions for Bipolar Disorder
    Alan Kozikowski; Fiscal Year: 2009
    ..using their patented SmartCube technology. ..
  15. Chemistry and Biology of 5-HT2C Receptor Ligands for Drug Abuse
    Alan Kozikowski; Fiscal Year: 2007
    ....
  16. Chemistry and Pharmacology of a New Nicotine Ligands
    Alan Kozikowski; Fiscal Year: 2003
    ..Functional activity will be evaluated using established 86RbC1 efflux assays and/or whole cell patch clamp measurements. ..
  17. CHEMICAL AND PHARMACOLOGICAL STUDIES OF COCAINE ANALOGS
    Alan Kozikowski; Fiscal Year: 2002
    ....
  18. CHEMICAL & PHARMACOLOGICAL STUDIES OF COCAINE ANALOGUES
    Alan Kozikowski; Fiscal Year: 1999
    ..Results of our efforts to date which include the discovery of a weak cocaine antagonist are detailed in the Preliminary Studies Section. ..
  19. DESIGN OF LIGANDS SELECTIVE FOR THE DAG SUPERFAMILY
    Alan Kozikowski; Fiscal Year: 1999
    ..To assess the effect of alterations in the ligand's hydrophobic side chain on its tumor promoting activity, studies of skin hyperplasia will be conducted. ..
  20. BIOLOGICAL STUDIES OF PIPERIDINE ANALOGS OF COCAINE
    Alan Kozikowski; Fiscal Year: 1999
    ..4. For compounds meeting set criteria, to further evaluate their behavioral pharmacological profile in animals using intravenous drug self-administration and drug discrimination procedures. ..
  21. DESIGN OF LIGANDS SELECTIVE FOR THE DAG SUPERFAMILY
    Alan Kozikowski; Fiscal Year: 2000
    ..To assess the effect of alterations in the ligand's hydrophobic side chain on its tumor promoting activity, studies of skin hyperplasia will be conducted. ..
  22. DESIGN OF LIGANDS SELECTIVE FOR THE DAG SUPERFAMILY
    Alan Kozikowski; Fiscal Year: 2002
    ..To assess the effect of alterations in the ligand's hydrophobic side chain on its tumor promoting activity, studies of skin hyperplasia will be conducted. ..
  23. BIOLOGICAL STUDIES OF PIPERIDINE ANALOGS OF COCAINE
    Alan Kozikowski; Fiscal Year: 2001
    ..4. For compounds meeting set criteria, to further evaluate their behavioral pharmacological profile in animals using intravenous drug self-administration and drug discrimination procedures. ..
  24. CHEMICAL AND PHARMACOLOGICAL STUDIES OF COCAINE ANALOGS
    Alan Kozikowski; Fiscal Year: 2001
    ....
  25. DESIGN OF LIGANDS SELECTIVE FOR THE DAG SUPERFAMILY
    Alan Kozikowski; Fiscal Year: 2001
    ..To assess the effect of alterations in the ligand's hydrophobic side chain on its tumor promoting activity, studies of skin hyperplasia will be conducted. ..
  26. CHEMICAL AND PHARMACOLOGICAL STUDIES OF COCAINE ANALOGS
    Alan Kozikowski; Fiscal Year: 2000
    ....
  27. BIOLOGICAL STUDIES OF PIPERIDINE ANALOGS OF COCAINE
    Alan Kozikowski; Fiscal Year: 2000
    ..4. For compounds meeting set criteria, to further evaluate their behavioral pharmacological profile in animals using intravenous drug self-administration and drug discrimination procedures. ..
  28. Chemistry and Biology of 5-HT2C Receptor Ligands for Drug Abuse
    ALAN PAUL KOZIKOWSKI; Fiscal Year: 2010
    ....