Pulrodemstat HCl is an orally active, selective and potent lysine demethylase-1 (LSD1) inhibitor, and a selective KDM1A inhibitor, with anticancer and anti-proliferative activities, inhibiting HNSCC cell proliferation and migration Inhibits the growth of head and neck squamous cell carcinoma by triggering apoptosis.

H1417:4 nM (EC50), CD11b:7 nM (EC50), H209:3 nM (EC50)

Pulrodemstat HCl was effective in inducing the target cell differentiation marker CD11b in the THP-1 cell line with an EC50 of 7 nM; the antiproliferative activity in AML Kasumi-1 cells had an EC50 of 2 nM.[1]
Pulrodemstat HCl acts for 4 days and inhibits GRP in a dose-dependent manner at pharmacologically useful concentrations (H209-EC50=3 nM and H1417-EC50=4 nM).Pulrodemstat HCl acts for 12 days and produces potent antiproliferative activity (H1417-EC50=6 nM) in SCLC cells. [1]

In a patient-derived xenograft SCLC model, daily oral administration of 5 mg/kg Pulrodemstat HCl for 30 days significantly inhibited tumor growth. In addition, in a SCLC xenograft mouse model (H1417), once-daily treatment with Pulrodemstat HCl for 4 consecutive days significantly down-regulated GRP mRNA levels at 2.5 mg/kg, while the strongest inhibition of GRP expression was observed at 5 mg/kg. [1]
After intravenous injection of 5 mg/kg Pulrodemstat HCl, the systemic clearance was 32.4 mL/min/kg, the elimination half-life was 2 h, and the volume of distribution was high at 7.5 L/kg. When the same dose was administered orally, the drug was well absorbed, with an AUC (0-24h) of 1.8 μM-h, Cmax of 0.36 μM, oral bioavailability of 0.36 μM, and oral bioavailability of 1.8 μM/kg. μM and oral bioavailability was 32%. [1]