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Derivatives of Procaspase-Activating Compound 1 (PAC-1) and their Anticancer Activities.

ABSTRACT: PAC-1 induces the activation of procaspase-3 in vitro and in cell culture by chelation of inhibitory labile zinc ions via its ortho-hydroxy-N-acylhydrazone moiety. First reported in 2006, PAC-1 has shown promise in cell culture and animal models of cancer, and a Phase I clinical trial in cancer patients began in March 2015 (NCT02355535). Because of the considerable interest in this compound and a well-defined structure-activity relationship, over 1000 PAC-1 derivatives have been synthesized in an effort to vary pharmacological properties such as potency and pharmacokinetics. This article provides a comprehensive examination of all PAC-1 derivatives reported to date. A survey of PAC-1 derivative libraries is provided, with an indepth discussion of four derivatives on which extensive studies have been performed.

SUBMITTER: Roth HS

PROVIDER: S-EPMC4968085 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Derivatives of Procaspase-Activating Compound 1 (PAC-1) and their Anticancer Activities.

Roth Howard S HS Hergenrother Paul J PJ

Current medicinal chemistry 20160101 3

PAC-1 induces the activation of procaspase-3 in vitro and in cell culture by chelation of inhibitory labile zinc ions via its ortho-hydroxy-N-acylhydrazone moiety. First reported in 2006, PAC-1 has shown promise in cell culture and animal models of cancer, and a Phase I clinical trial in cancer patients began in March 2015 (NCT02355535). Because of the considerable interest in this compound and a well-defined structure-activity relationship, over 1000 PAC-1 derivatives have been synthesized in a ...[more]

PMID: 26630918

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