Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 50, Issue 15, Pages 3751-3755Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm070506t
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Funding
- NCI NIH HHS [CA121952] Funding Source: Medline
- NHLBI NIH HHS [HL13851] Funding Source: Medline
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A series of isatin sulfonamide analogs having a Michael acceptor were prepared and their potencies for inhibiting caspase-1, -3, -6, -7, and -8 were evaluated. These compounds have nanomolar potency for inhibiting the executioner caspases, caspase-3 and caspase-7, and have a low potency for inhibiting caspase-1, caspase-6, and caspase-8. The inhibition mechanism was investigated through NMR studies of the reaction between 11d and benzylmercaptan as a model for Cys-285 in the active site of caspase-3.
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