IPI-9119 is an orally active, selective and irreversible FASN inhibitor with an IC50 of 0.3 nM in vitro biochemical assay. IPI-9119 inhibits tumor growth of castration-resistant prostate cancer (CRPC) xenografts mouse models.
IC50&Target
IC50: 0.3 nM (FASN)
体外研究
IPI-9119 inhibits FASN in cellular occupancy assays (IC50∼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.
Cell Viability Assay
Cell 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 Analysis
Cell 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 Analysis
Cell 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.
体内研究
IPI-9119 (SC pump infusion; 0.5 μL/h; 100 mg/mL; for 28 days) inhibits tumor growth of CRPC xenografts mouse models.
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.
分子式
C24H19F2N5O5
分子量
495.43
CAS号
1346564-56-4
运输条件
Room temperature in continental US; may vary elsewhere.