Research Topics
| Thomas D PenningSummaryAffiliation: Abbott Laboratories Country: USA Publications
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Publications
Synthesis of pyrazoles and isoxazoles as potent alpha(v)beta3 receptor antagonistsThomas D Penning
Department of Medicinal Chemistry, Pfizer Global Research and Development, 4901 Searle Parkway, Skokie, IL 60077, USA
Bioorg Med Chem Lett 16:3156-61. 2006..Compounds were synthesized in a straightforward manner from readily available glutarate precursors...- The PARP inhibitor, ABT-888 potentiates temozolomide: correlation with drug levels and reduction in PARP activity in vivoJoAnn P Palma
Abbott Laboratories, Cancer Research, Abbott Park, IL 60064, USA
Anticancer Res 28:2625-35. 2008..Potentiation of TMZ activity by ABT-888 correlated with drug levels and inhibition of PARP activity in vivo. ABT-888 is in Phase 1 trials using a validated ELISA based on the assay developed here to assess pharmacological effect... - Discovery and SAR of 2-(1-propylpiperidin-4-yl)-1H-benzimidazole-4-carboxamide: A potent inhibitor of poly(ADP-ribose) polymerase (PARP) for the treatment of cancerThomas D Penning
Cancer Research, GPRD, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
Bioorg Med Chem 16:6965-75. 2008.... - Optimization of phenyl-substituted benzimidazole carboxamide poly(ADP-ribose) polymerase inhibitors: identification of (S)-2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-1H-benzimidazole-4-carboxamide (A-966492), a highly potent and efficacious inhibitorThomas D Penning
Cancer Research, Abbott Laboratories 100 Abbott Park Road, Abbott Park, Illinois 60064, USA
J Med Chem 53:3142-53. 2010..It also demonstrated good in vivo efficacy in a B16F10 subcutaneous murine melanoma model in combination with temozolomide and in an MX-1 breast cancer xenograft model both as a single agent and in combination with carboplatin... - Small-molecule PARP modulators--current status and future therapeutic potentialThomas D Penning
Abbott Laboratories, Cancer Research, Global Pharmaceutical Research and Development, 100 Abbott Park Road, Abbott Park, IL 60064, USA
Curr Opin Drug Discov Devel 13:577-86. 2010..This review focuses on new developments in lead clinical PARP inhibitors, recent disclosures of new inhibitors and the potential use of PARP-1 inhibitors in new disease settings... - Synthesis of cinnamic acids and related isosteres as potent and selective alpha v beta 3 receptor antagonistsThomas D Penning
Department of Medicinal Chemistry, Pfizer Global Research and Development, 4901 Searle Parkway, Skokie, IL 60077, USA
Bioorg Med Chem Lett 14:1471-6. 2004..These compounds were synthesized from readily available starting materials using either Heck or Mitsunobu coupling conditions... - Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancerThomas D Penning
Cancer Research, Pharmacokinetics, GPRD, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064, USA
J Med Chem 52:514-23. 2009.... - Synthesis and evaluation of a new generation of orally efficacious benzimidazole-based poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors as anticancer agentsYunsong Tong
Cancer Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA
J Med Chem 52:6803-13. 2009..In addition, these two molecules exhibited potent oral in vivo efficacy in potentiating the cytotoxic agent temozolomide in a B16F10 murine melanoma model... - Synthesis and SAR of novel, potent and orally bioavailable benzimidazole inhibitors of poly(ADP-ribose) polymerase (PARP) with a quaternary methylene-amino substituentGui Dong Zhu
Cancer Research, GPRD, Abbott Laboratories, Abbott Park, IL 60064, USA
Bioorg Med Chem Lett 18:3955-8. 2008..In vivo efficacy data in a B16F10 murine flank melanoma model in combination with temozolomide (TMZ) are described for two optimized analogs... - Synthesis and SAR of novel tricyclic quinoxalinone inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1)Julie Miyashiro
Cancer Research, GPRD, Abbott Laboratories, 100 Abbott Park Rd, Abbott Park, IL 60064, USA
Bioorg Med Chem Lett 19:4050-4. 2009..The tricyclic quinoxalinone class is sensitive to modifications of both the amine substituent and the tricyclic core. The synthesis and structure-activity relationship studies are presented... - Syntheses of potent, selective, and orally bioavailable indazole-pyridine series of protein kinase B/Akt inhibitors with reduced hypotensionGui Dong Zhu
Cancer Research, Preclinical Safety, Structural Biology, Integrative Pharmacology, GPRD, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6101, USA
J Med Chem 50:2990-3003. 2007..6 nM vs Akt), selectivity, and improved cardiovascular safety profile. The SARs, pharmacokinetic profile, and CV safety of selected Akt inhibitors will be discussed... - ABT-888 confers broad in vivo activity in combination with temozolomide in diverse tumorsJoAnn P Palma
Abbott Laboratories, Cancer Research, Abbott Park, Illinois 60064, USA
Clin Cancer Res 15:7277-90. 2009..We investigated ABT-888+TMZ combination therapy in multiple xenograft models representing various human tumors having different responses to TMZ... - Synthesis of 2,5-thiazole butanoic acids as potent and selective alpha(v)beta3 integrin receptor antagonists with improved oral pharmacokinetic propertiesJohn A Wendt
Department of Medicinal Chemistry, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA
Bioorg Med Chem Lett 16:845-9. 2006..These analogs were demonstrated to have high bioavailability relative to other relative heterocyclic analogs... - ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor modelsCherrie K Donawho
Abbott Laboratories, Abbott Park, Illinois 60064 6074, USA
Clin Cancer Res 13:2728-37. 2007..To evaluate the preclinical pharmacokinetics and antitumor efficacy of a novel orally bioavailable poly(ADP-ribose) polymerase (PARP) inhibitor, ABT-888... - Discovery and SAR of substituted 3-oxoisoindoline-4-carboxamides as potent inhibitors of poly(ADP-ribose) polymerase (PARP) for the treatment of cancerViraj B Gandhi
Cancer Research, GPRD, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
Bioorg Med Chem Lett 20:1023-6. 2010..An additional hydrogen bond interaction of the piperidine nitrogen to Gly-888 also contributes to the binding affinity of 1e to PARP-1... - Synthesis of imidazopyridines and purines as potent inhibitors of leukotriene A4 hydrolaseThomas D Penning
Department of Medicinal Chemistry, Pharmacia Corporation, 4901 Searle Parkway, Skokie, IL 60077, USA
Bioorg Med Chem Lett 13:1137-9. 2003..Imidazopyridine and purine analogues are specifically highlighted with several demonstrating excellent potency in our in vitro assays, as well as good oral activity in a mouse ex vivo assay... - Pyrrolidine and piperidine analogues of SC-57461A as potent, orally active inhibitors of leukotriene A(4) hydrolaseThomas D Penning
Department of Medicinal Chemistry, Pharmacia Corporation, Skokie, IL 60077, USA
Bioorg Med Chem Lett 12:3383-6. 2002..These efforts led to the identification of SC-56938 (14) as a potent, orally active inhibitor of LTA(4) hydrolase... - Discovery of 3H-benzo[4,5]thieno[3,2-d]pyrimidin-4-ones as potent, highly selective, and orally bioavailable inhibitors of the human protooncogene proviral insertion site in moloney murine leukemia virus (PIM) kinasesZhi Fu Tao
Cancer Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA
J Med Chem 52:6621-36. 2009..ADME profiling of 14j suggested a long half-life in both human and mouse liver microsomes, good permeability, modest protein binding, and no CYP inhibition below 20 muM concentration... - Aminopyrimidinone cdc7 kinase inhibitorsKeith W Woods
Abbott Laboratories, 100 Abbott Park Rd, R47S AP10 307, Abbott Park, IL 60064 6101, USA
Bioorg Med Chem Lett 22:1940-3. 2012..A wide range of amine substitutions give potent compounds with activities (K(i)) less than 1nM. Kinase selectivity is reasonable and cytotoxicity corresponds to inhibition of MCM2 phosphorylation... - Isoxazolo[3,4-b]quinoline-3,4(1H,9H)-diones as unique, potent and selective inhibitors for Pim-1 and Pim-2 kinases: chemistry, biological activities, and molecular modelingYunsong Tong
Cancer Research, Global Pharmaceutical R and D, Abbott Laboratories, R47S, AP10, 100 Abbott Park Road, Abbott Park, IL 60064, USA
Bioorg Med Chem Lett 18:5206-8. 2008..5 and 43.5 nM against Pim-1 and Pim-2, respectively. Compound 19 also exhibited an activity profile with a high degree of kinase selectivity... - Synthesis of potent leukotriene A(4) hydrolase inhibitors. Identification of 3-[methyl[3-[4-(phenylmethyl)phenoxy]propyl]amino]propanoic acidThomas D Penning
Department of Medicinal Chemistry, Pharmacia Corporation, 4901 Searle Parkway, Skokie, IL 60077, USA
J Med Chem 45:3482-90. 2002..The efforts leading to the identification of clinical candidate SC-57461A (8d, 3-[methyl[3-[4-(phenylmethyl)phenoxy]propyl]amino]propanoic acid) are described... - Iniparib nonselectively modifies cysteine-containing proteins in tumor cells and is not a Bona Fide PARP inhibitorXuesong Liu
Cancer Research, Advanced Technology, and Process R and D, Abbott Laboratories, Abbott Park, IL 60064, USA
Clin Cancer Res 18:510-23. 2012..In this study, we compare the biologic activities of two different structural classes of NAD(+)-competitive compounds with iniparib and its C-nitroso metabolite... - Convergent, parallel synthesis of a series of beta-substituted 1,2,4-oxadiazole butanoic acids as potent and selective alpha(v)beta3 receptor antagonistsMark L Boys
Department of Chemistry, PfizerGlobal Research and Development, 2800 Plymouth Rd, Ann Arbor, MI 48105, USA
Bioorg Med Chem Lett 16:839-44. 2006..In whole cells, the majority of these analogs also demonstrated modest selectivity against other alpha(v) integrins such as alpha(v)beta1 and alpha(v)beta6...