Pulrodemstat (CC-90011) is a highly potent and selective inhibitor of lysine specific demethylase-1 (LSD1), exhibiting a reversible mode of action and oral bioavailability. With an impressive IC50 of 0.25 nM, Pulrodemstat effectively suppresses LSD1 enzymatic activity while demonstrating minimal inhibition of LSD2, MOA-A, and MAO-B enzymes. Additionally, Pulrodemstat possesses remarkable anticancer properties, promoting differentiation in acute myeloid leukemia (AML) and small cell lung cancer (SCLC) cells.

LSD1:0.25 nM (IC50)

Pulrodemstat (CC-90011, Compound 11) induces the cellular differentiation marker CD11b in the THP-1 cell line with an EC50 of 7 nM and shows significant antiproliferative effects in AML Kasumi-1 cells (EC50 of 2 nM) [1]. Additionally, Pulrodemstat suppresses GRP in a dose-dependent manner over four days, achieving pharmacologically relevant concentrations (EC50 of 3 nM in H209 and 4 nM in H1417 cells) [1]. A 12-day treatment with Pulrodemstat also results in notable antiproliferative activity in SCLC cells (EC50 of 6 nM in H1417 cells), consistent with GRP suppression [1].

Pulrodemstat (CC-90011; 5 mg/kg; orally; daily for 30 days) significantly inhibits tumor growth in patient-derived xenograft models of small cell lung carcinoma (SCLC), with a tumor growth inhibition rate of 78% and no weight loss in BALB/c nude mice. Additionally, daily oral doses for 4 days result in notable downregulation of GRP mRNA levels, achieving maximum GRP suppression at a 5 mg/kg dosage in a SCLC human tumor xenograft (H1417) mouse model. Pharmacokinetic studies show that Pulrodemstat (Compound 11; 5 mg/kg) has a systemic clearance of 32.4 mL/min/kg, an elimination half-life of 2 hours, and a high volume of distribution of 7.5 L/kg following intravenous administration. After oral administration, Pulrodemstat exhibits good absorption with an area under the curve (AUC 0-24h) of 1.8 μM·h, a maximum concentration (Cmax) of 0.36 μM, and an oral bioavailability of 32%.