CC-90011 is a potent and orally active LSD1 inhibitor. It is in phase I clinical study of CC-90011 in patients (pts) with advanced unresectable solid tumors and R/R NHL.
CC-90011 benzenesulfonate acts as a potent, selective, reversible, and orally active lysine specific demethylase-1 (LSD1) inhibitor with an IC50 of 0.25 nM. It exhibits minimal enzymatic inhibition towards LSD2, MAO-A, and MAO-B. CC-90011 benzenesulfonate promotes differentiation in acute myeloid leukemia (AML) and small cell lung cancer (SCLC) cells, demonstrating significant anticancer efficacy [1].
体内研究
CC-90011 treatment (5 mg/kg; oral administration; daily; for 30 days) suppresses tumor growth in patient-derived xenograft SCLC models [1].
CC-90011 treatment (once a day; for 4 days) leads to significant downregulation of GRP mRNA levels at 2.5 mg/kg and maximal suppression of GRP at 5 mg/kg in SCLC human tumor xenograft (H1417) mice [1].
Following intravenous (i.v.) administration, CC-90011 (5 mg/kg) displays a systemic clearance of 32.4 mL/min/kg, an elimination half-life of 2 hours, and a large volume of distribution at 7.5 L/kg. After oral administration, CC-90011 (5 mg/kg) is quickly absorbed, showing an AUC0-24h of 1.8 μM·h, a Cmax of 0.36 μM, and an oral bioavailability of 32% [1].
体外研究
CC-90011 effectively induces the on-target cellular differentiation marker CD11b in the THP-1 cell line with an EC50 of 7 nM and exhibits antiproliferative effects in AML Kasumi-1 cells with an EC50 of 2 nM [1].
Treatment with CC-90011 suppresses GRP in a dose-dependent manner at pharmacologically effective concentrations (EC50=3 nM, H209 and 4 nM, H1417) over 4 days. A 12-day treatment of SCLC cells with CC-90011 demonstrates strong antiproliferative effects (EC50=6 nM, H1417), associated with GRP suppression [1].
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