IPI-9119 (C09-1140-037)

IPI-9119 is an orally active, selective and irreversible FASN inhibitor with an IC 50 of 0.3 nM in vitro biochemical assay. IPI-9119 inhibits tumor growth of castration-resistant prostate cancer (CRPC) xenografts mouse modelsIn VitroIPI-9119 inhibits FASN in cellular occupancy assays (IC 50 ∼10nM), and shows more than 400-fold selectivity against several additional serine hydrolases. IPI-9119 (0.1-0.5 μM; 6 days) inhibits cell growth and induces cell cycle arrest, apoptosis. IPI-9119 (0.05-5 μM; 6 days) inhibits AR-FL and AR-V7 protein expression. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: Prostate cancer (PCa) cells (AD LNCaP, AI C4-2, LNCaP-95 and 22Rv1 AI cells) Concentration: 0.1, 0.5 μM Incubation Time: 6 days Result: Inhibited PCa cell growth. Had no growth inhibition in FASN KO PCa cells. Cell Cycle AnalysisCell Line: PCa cells Concentration: 0.1, 0.5 μM Incubation Time: 6 days Result: Reduced the proportion of S-phase cells and increased that of G0/G1-, sub-G1–phase cells and decreased expression of cyclin A2. Western Blot AnalysisCell Line: PCa cells Concentration: 0.05, 0.1, 0.25, 0.5, 5 μM Incubation Time: 6 days Result: Significantly decreased AR-FL protein levels in AD LNCaP, AI C4-2 cells (expressing only AR-FL) and reduced the expression of AR-V7 in LNCaP-95, 22Rv1 AI cells driven by this variant.In VivoIPI-9119 (SC pump infusion; 0.5 μL/h; 100 mg/mL; for 28 days) inhibits tumor growth of CRPC xenografts mouse models . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: 8-10-week male Ncr Nu Castrated mice or castrated NOD male SCID with 22Rv1 or LNCaP-95 cells Dosage: 100 mg/mL Administration: SC pump infusion (0.5 μL/h; 100 mg/mL); for 28 days Result: Inhibited tumor growth of castration-resistant prostate cancer (CRPC) xenografts mouse models.Form:SolidIC50& Target:IC50: 0.3 nM (FASN). Specification: 0.98 Molecular Formula: C24H19F2N5O5 Molecular Weight: 495.43 PubChem CID: 68208572 Isomeric SMILES: CC(C)N(C1=C(C=C(C=C1)C(=O)O)OC2=CC=CC=C2)C(=O)N3C(=O)N(N=N3)C4=C(C=CC=C4F)F