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Overview
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Background
UC-112[5-((benzyloxy)methyl)-7-(pyrrolidin-1-ylmethyl)quinolin-8-ol], is inhibitor of inhibitor of apoptosis protein (IAP).[1]
Inhibitor of apoptosis protein (IAP) family is overexpressed in most human cancer cells, but nearly isn’t expressed in adult differentiated tissues. Inhibitor of apoptosis (IAP) proteins are widely considered as promising drug-resistant tumors drug targets. [1,2]
UC-112 strongly activates caspase-3/7 and caspase-9 activities, and selectively reduce surviving level at a concentration as low as 1 mM. Coincubation of UC-112 with a known proteasome inhibitor Z-Leu-Leu-Leu-CHO (MG-132) rescued survivin inhibition. As a single agent, UC-112 strongly inhibits tumor growth and reduces both X chromosomelinked IAP and survivin levels in an A375 human melanoma xenograft model in vivo.[1]
UC-112 inhibits tumor cell growth in several cancer cell lines in vitro and suppresses melanoma tumor growth in vivo. Mechanistic studies indicated that UC-112 selectively inhibits survivin expression and induces strong cancer cell apoptosis. UC-112 could efficiently inhibit tumor cell proliferation by down regulating the level of IAPs, especially survivin protein.[1,2][1] Wang J, Li W. Discovery of novel second mitochondria-derived activator of caspase mimetics as selective inhibitor of apoptosis protein inhibitors. J Pharmacol Exp Ther. 2014 May;349(2):319-29.
[2] Xiao M, Wang J, Lin Z, etal. , Design, Synthesis and Structure-Activity Relationship Studies of Novel Survivin Inhibitors with Potent Anti-Proliferative Properties. PLoS One. 2015 Jun 12;10(6):e0129807.
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