Description
PAC-1 (Procaspase Activating Compound 1) has been identified through high-throughput screening as a compound that may enhance the enzymatic activity of procaspase-3 in vitro. Procaspase-3 may be useful as an anticancer strategy due to its low frequency of mutations in cancer and expression of its enzyme in several types of cancers. PAC-1 converts procaspase-3 to active caspase-3 in vitro by chelating zinc ions and thereby inducing cell death in the tumor cells. In multiple cancer cell lines, PAC-1 was shown to trigger endoplasmic reticulum stress signaling and induce autophagy and mitochondria-mediated apotosis.
References
Sarkar A, Balakrishnan K, Chen J, et al. Molecular evidence of Zn chelation of the procaspase activating compound B-PAC-1 in B cell lymphoma. Oncotarget. 2016 Jan 19;7(3):3461-3476. PMID: 26658105.
Roth HS, Hergenrother PJ. Derivatives of procaspase-activating compound 1 (PAC-1) and their anticancer activities. Curr Med Chem. 2016;23(3):201-241. PMID: 26630918.
Seervi M, Sobhan PK, Joseph J, et al. ERO1alpha-dependent endoplasmic reticulum-mitochondrial calcium flux contributes to ER stress and mitochondrial permeabilization by procaspase-activating compound-1 (PAC-1). Cell Death Dis. 2013 Dec 19;4:e968. PMID: 24357799.
Lucas PW, Schmit JM, Peterson QP, et al. Pharmacokinetics and derivation of an anticancer dosing regimen for PAC-1, a preferential small molecule activator of procaspase-3, in healthy dogs. Invest New Drugs. 2011 Oct;29(5):901-911. PMID: 20499133.
Peterson QP, Goode DR, West DC, et al. PAC-1 activates procaspase-3 in vitro through relief of zinc-mediated inhibition. J Mol Biol. 2009 Apr 24;388(1):144-158. PMID: 19281821.
