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.
Keywords: PAC-1, procaspase-3, zinc, apoptosis, cancer, library.
Current Medicinal Chemistry
Title:Derivatives of Procaspase-Activating Compound 1 (PAC-1) and their Anticancer Activities
Volume: 23 Issue: 3
Author(s): Howard S. Roth and Paul J. Hergenrother
Affiliation:
Keywords: PAC-1, procaspase-3, zinc, apoptosis, cancer, library.
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.
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Cite this article as:
Roth S. Howard and Hergenrother J. Paul, Derivatives of Procaspase-Activating Compound 1 (PAC-1) and their Anticancer Activities, Current Medicinal Chemistry 2016; 23 (3) . https://dx.doi.org/10.2174/0929867323666151127201829
DOI https://dx.doi.org/10.2174/0929867323666151127201829 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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