Research Topics
| Allan WissnerSummaryAffiliation: Wyeth Research Country: USA Publications
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Detail Information
Publications
Dual irreversible kinase inhibitors: quinazoline-based inhibitors incorporating two independent reactive centers with each targeting different cysteine residues in the kinase domains of EGFR and VEGFR-2Allan Wissner
Chemical and Screening Sciences and Oncology Research, Wyeth Research, 401 N Middletown Road, Pearl River, NY 10965, USA
Bioorg Med Chem 15:3635-48. 2007..The relative dependence of the IC(50) values on the concentration of ATP used in the assays suggests that these compounds appear to function as irreversible inhibitors of each kinase...- Syntheses and EGFR and HER-2 kinase inhibitory activities of 4-anilinoquinoline-3-carbonitriles: analogues of three important 4-anilinoquinazolines currently undergoing clinical evaluation as therapeutic antitumor agentsAllan Wissner
Chemical Sciences and Oncology and Immunoinflammatory Research, Wyeth Research, 401N Middletown Road, Pearl River, NY 10965, USA
Bioorg Med Chem Lett 12:2893-7. 2002..The EGFR and HER-2 kinase inhibitory activities and the cell growth inhibition of the two series are compared with each other and with the clinical lead EKB-569. Similar activities are observed between these two series... 
The development of HKI-272 and related compounds for the treatment of cancerAllan Wissner
Chemical and Screening Sciences, Wyeth Research, 401 N Middletown Road, Pearl River, NY 10965, USA
Arch Pharm (Weinheim) 341:465-77. 2008..The promising interim clinical trial results for HKI-272 and EKB-569 in treating colon, lung, and breast cancers are summarized...- Synthesis and structure-activity relationships of 6,7-disubstituted 4-anilinoquinoline-3-carbonitriles. The design of an orally active, irreversible inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) and the human epiAllan Wissner
Chemical Sciences, Oncology and Immunoinflammatory Research, Wyeth Research, 401 North Middletown Road, Pearl River, New York 10965, USA
J Med Chem 46:49-63. 2003..One compound, 5 (EKB-569), which shows excellent oral in vivo activity, was selected for further studies and is currently in phase I clinical trials for the treatment of cancer... - Syntheses and EGFR kinase inhibitory activity of 6-substituted-4-anilino [1,7] and [1,8] naphthyridine-3-carbonitrilesAllan Wissner
Chemical and Screening Sciences and Oncology Research, Wyeth Research, 401N Middletown Road, Pearl River, NY 10965, USA
Bioorg Med Chem Lett 14:1411-6. 2004..Compounds having a 1,7-naphthyridine core structure can retain high potency while those with a 1,8-naphthyridine core are significantly less active. These results are consistent with molecular modeling observations... - Optimization of 6,7-disubstituted-4-(arylamino)quinoline-3-carbonitriles as orally active, irreversible inhibitors of human epidermal growth factor receptor-2 kinase activityHwei Ru Tsou
Chemical and Screening Sciences, Wyeth Research, 401 North Middletown Road, Pearl River, New York 10965, USA
J Med Chem 48:1107-31. 2005..Furthermore, it demonstrated excellent oral activity, especially in HER-2 overexpressing xenografts. Compound 25o (HKI-272) was selected for further studies and is currently in phase I clinical trials for the treatment of cancer... - 2-(Quinazolin-4-ylamino)-[1,4]benzoquinones as covalent-binding, irreversible inhibitors of the kinase domain of vascular endothelial growth factor receptor-2Allan Wissner
Chemical and Screening Sciences and Oncology Research, Wyeth Research, 401 N. Middletown Road, Pearl River, New York 10965, USA
J Med Chem 48:7560-81. 2005..Unequivocal evidence, from mass spectral studies, indicates that these inhibitors form a covalent interaction with Cys-1045. One member of this series displays antitumor activity in an in vivo model... - Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinaseSridhar K Rabindran
Department of Oncology, Wyeth Research, Pearl River, New York, USA
Cancer Res 64:3958-65. 2004..On the basis of its favorable preclinical pharmacological profile, HKI-272 has been selected as a candidate for additional development as an antitumor agent in breast and other HER-2-dependent cancers... - Synthesis and evaluation of 4-anilino-6,7-dialkoxy-3-quinolinecarbonitriles as inhibitors of kinases of the Ras-MAPK signaling cascadeDan Berger
Chemical Sciences, Wyeth Research, Pearl River, NY 10965, USA
Bioorg Med Chem Lett 13:3031-4. 2003..Secondary cellular assays revealed that a compound possessing the appropriate aniline substituents inhibited MEK1 as well as MAPK phosphorylation, thereby acting as a dual inhibitor of the Ras-MAPK signaling cascade... - Synthesis and PKCtheta inhibitory activity of a series of 4-indolylamino-5-phenyl-3-pyridinecarbonitrilesRussell G Dushin
Wyeth Research, Chemical Sciences, 401 N Middletown Road, Pearl River, NY 10965, USA
Bioorg Med Chem Lett 19:2461-3. 2009..This study led to the discovery of compound 12d, which had an IC(50) value of 18nM for the inhibition of PKCtheta... - Substituted 4-anilino-7-phenyl-3-quinolinecarbonitriles as Src kinase inhibitorsDan Berger
Chemical Sciences, Wyeth Research, Pearl River, NY 10965, USA
Bioorg Med Chem Lett 12:2989-92. 2002..The best compounds are low nanomolar inhibitors of Src kinase, and have potent activity against Src-transformed fibroblast cells... - The identification of 8,9-dimethoxy-5-(2-aminoalkoxy-pyridin-3-yl)-benzo[c][2,7]naphthyridin-4-ylamines as potent inhibitors of 3-phosphoinositide-dependent kinase-1 (PDK-1)Thomas Nittoli
Chemical Sciences, Wyeth Research, 401 N Middletown Road, Pearl River, NY 10965, USA
Eur J Med Chem 45:1379-86. 2010.... - Benzo[c][2,7]naphthyridines as inhibitors of PDK-1Kyung Hee Kim
Wyeth Research, Chemical Sciences, 401 N Middletown Road, Pearl River, NY 10965, USA
Bioorg Med Chem Lett 19:5225-8. 2009..The synthesis and SAR of this series of compounds are presented as well as the X-ray crystal structure of one of these analogs in a complex with PDK-1... - 8-Anilinoimidazo[4,5-g]quinoline-7-carbonitriles as Src kinase inhibitorsDan Berger
Chemical Sciences, Wyeth Ayerst Research, Pearl River, NY 10965, USA
Bioorg Med Chem Lett 12:2761-5. 2002..Several aniline substituents were surveyed, as well as water-solubilizing groups at the C-2 and N-3 positions. Potent Src inhibitors were identified, with N-3 providing the best position for an additional water-solubilizing group... - 4-Anilino-3-cyanobenzo[g]quinolines as kinase inhibitorsNan Zhang
Chemical Sciences, Wyeth Ayerst Research, Pearl River, NY 10965, USA
Bioorg Med Chem Lett 12:423-5. 2002..For Src kinase inhibition, the best activity is obtained when both the 7- and 8-positions are substituted with alkoxy groups. Several of these kinase inhibitors show potent growth inhibitory activity in tumor cells... - Identification, characterization and initial hit-to-lead optimization of a series of 4-arylamino-3-pyridinecarbonitrile as protein kinase C theta (PKCtheta) inhibitorsDerek C Cole
Chemical and Screening Sciences, Wyeth Research, Pearl River, New York 10965, USA
J Med Chem 51:5958-63. 2008..Compound 4p also inhibited IL-2 production in antiCD3/anti-CD28 activated T cells enriched from splenocytes... 
Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinibEunice L Kwak
Center for Molecular Therapeutics, Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
Proc Natl Acad Sci U S A 102:7665-70. 2005..Our findings suggest that one of these, HKI-272, may prove highly effective in the treatment of EGFR-mutant NSCLCs, including tumors that have become resistant to gefitinib or erlotinib...