IRC-083927 (hydrochloride)

IRC-083927 hydrochloride is an orally active tubulin inhibitor. IRC-083927 hydrochloride binds competitively to the colchicine-binding site on tubulin, inhibits tubulin polymerization, disrupts the microtubule cytoskeleton, and arrests the cell cycle at the G2-M phase. IRC-083927 (hydrochloride) can be used in research related to human cervical cancer, hormone-independent breast cancer, pancreatic cancer, prostate cancer, and small cell lung cancer^[1][2]. In Vitro:IRC-083927 (5-100 nM) hydrochloride disrupts and depolymerizes the microtubule cytoskeleton in human prostate cancer DU-145 cells^[1].
IRC-083927 (72-96 h) hydrochloride inhibits the proliferation of human tumor cell lines including MIA PaCa-2, MDA-MB-231, DU-145, NCI-H69, NCI-H69/AR, NCI-H69/Lx4, A549, A549.EpoB40 and A549.EpoB480, with IC₅₀ values ranging from 7 μM to 42 μM. It remains active against cell lines that develop resistance to standard tubulin-binding agents via efflux pumps or tubulin mutations^[1].
IRC-083927 (10-20 nM; 11 days) hydrochloride inhibits endothelial cell proliferation and blocks angiogenesis in human umbilical vein endothelial cells (HUVECs) and their co-culture system with fibroblasts^[1].
IRC-083927 (10-60 nM; 24 h) hydrochloride arrests the cell cycle at the G2-M phase in human non-small cell lung cancer A549 cell line and its tubulin mutation-resistant A549.EpoB40 cells^[1].
IRC-083927 (5 μM; 60 min) hydrochloride inhibits tubulin polymerization in purified bovine brain tubulin^[1].
IRC-083927 (20 μM; 3 h) hydrochloride competitively inhibits the binding of labeled colchicine to purified tubulin in a cell-free system^[1]. In Vivo:IRC-083927 (2.5-5 mg/kg; p.o.; once daily for 5 consecutive days followed by 2 days of withdrawal; continuous treatment for 4 weeks) hydrochloride exerts a significant tumor growth inhibitory effect in a mouse model of subcutaneous xenografted human cervical cancer^[1].
IRC-083927 (5 mg/kg; administered orally; once daily for 5 consecutive days followed by 2 days of withdrawal; treated continuously for 4 weeks) hydrochloride exerts a significant tumor growth inhibitory effect in a mouse model of subcutaneous xenografted human breast cancer^[1].