Pulrodemstat

SKU: orb1691452

Description

Pulrodemstat (CC-90011) is a potent, selective, and orally bioavailable LSD1 inhibitor with demonstrated anticancer activity. It suppresses head and neck squamous cell carcinoma (HNSCC) growth in vitro by inhibiting cell proliferation and migration and inducing apoptosis, with supporting evidence from in vivo studies.

Research Area

Epigenetics & Chromatin

Key Properties

• CAS Number: 1821307-10-1
• MW: 451.47
• Purity: 98.89% (May vary between batches)
• Formula: C₂₄H₂₃F₂N₅O₂
• SMILES: N#CC1=CC=C(C=C1F)C=2N=C(N(C(=O)C2C=3C=CC(OC)=C(F)C3)C)N4CCC(N)CC4
• Target: Histone Demethylase

Bioactivity

• Target IC50:
  H1417 cells (12 days):6 nM (EC50)|Kasumi-1 cells:2 nM (EC50)|H209 cells (4 days):3 nM (EC50)|CD11b:7 nM (EC50)|LSD1:0.25 nM (IC50)|H1417 cells (4 days):4 nM (EC50)
• In Vivo:
  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. 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. 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%.
• In Vitro:
  Pulrodemstat is a potent, selective, reversible and orally active lysine-specific demethylase 1 (LSD1) inhibitor with an IC50 value of 0.25 nM. 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. 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.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Pulrodemstat, CC 90011, CC90011, CC-90011, LSD1-IN-7

Compound Identifiers

PubChem CID

118483201