Pulrodemstat (CC-90011) is an orally active, selective, and highly efficient lysine-specific demethylase-1 (LSD1) inhibitor with anticancer activity. It inhibits HNSCC cell proliferation and migration by triggering apoptosis and inhibiting head and neck squamous cell carcinoma growth.

LSD1:0.25 nM (IC50), H1417 cells (4 days):4 nM (EC50), CD11b:7 nM (EC50), H209 cells (4 days):3 nM (EC50), Kasumi-1 cells:2 nM (EC50), H1417 cells (12 days):6 nM (EC50)

Pulrodemstat is a potent, selective, reversible and orally active lysine-specific demethylase 1 (LSD1) inhibitor with an IC50 value of 0.25 nM. [1]
In the THP-1 cell line, Pulrodemstat strongly induced the expression of CD11b, a marker of target cell differentiation, with an EC50 value of 7 nM; furthermore, it showed antiproliferative effects in acute myeloid leukemia (AML) Kasumi-1 cells with an EC50 value of 2 nM. [1]
After 4 days of treatment, Pulrodemstat reduced the levels of growth regulatory protein (GRP) in a dose-dependent manner. At pharmacologically effective concentrations, its EC50 was 3 nM and 4 nM for H209 and H1417 cells, respectively. significant antiproliferative effects were observed after 12 days of Pulrodemstat treatment of small cell lung cancer (SCLC) cells (EC50 of 6 nM for H1417), which were associated with GRP inhibition.[1]

In a patient-derived xenograft SCLC model, once-daily oral administration of 5 mg/kg of Pulrodemstat for 30 consecutive days significantly inhibited tumor growth. [1]
Once-daily treatment with Pulrodemstat for 4 consecutive days resulted in a significant reduction in GRP mRNA levels in SCLC human tumor xenograft mice (H1417). Significant inhibition was observed at a dose of 2.5 mg/kg, with maximal effect at 5 mg/kg.[1]
After intravenous administration of 5 mg/kg of Pulrodemstat, the systemic clearance was 32.4 mL/min/kg, the elimination half-life was 2 hours, and the volume of distribution was 7.5 L/kg. 5 mg/kg of Pulrodemstat was readily absorbed by the oral route, and it had an AUC0-24h of 1.8 μM-h, with a maximal concentration (Cmax) of 0.36 μM, and an oral bioavailability of 32%. [1]