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

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:

• Department of Chemistry, University of Illinois, 261 Roger Adams Laboratory, Box 36-5, 600 S. Mathews Ave., Urbana, IL, 61801, USA.,United States

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.

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