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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

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

Author(s): Howard S. Roth and Paul J. Hergenrother

Volume 23, Issue 3, 2016

Page: [201 - 241] Pages: 41

DOI: 10.2174/0929867323666151127201829

Price: $65

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.


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