BMS-906024

BMS-906024 is an orally active and selective γ-secretase (gamma secretase) inhibitor. BMS-906024 is a potent pan-Notch receptors inhibitor with IC₅₀s of 1.6 nM, 0.7 nM, 3.4 nM, and 2.9 nM for Notch1, -2, -3, and -4 receptors, respectively. BMS-906024 demonstrates broad-spectrum antineoplastic activity^[1][2]. IC50 & Target: IC50: 1.6 nM (Notch1), 0.7 nM (Notch2), 3.4 nM (Notch3) and 2.9 nM (Notch4)^[2] In Vitro: BMS-906024 (5-100 nM; 72 hours) reduces Notch1 ICD levels in all six lung cancer cell lines. BMS-906024 at 100 nM, has no effect on total Notch1, and down-regulated Hes1 transcript^[1].
In cancer cell proliferation assays, BMS-906024 inhibits both leukemia (TALL-1) and triple-negative breast cancer (MDA-MB-468) cells with IC₅₀ of ～4 nM^[2].
BMS-906024 (100 nM; for 72 hours) enhances the anti-tumor activity of Paclitaxel in vitro^[1].
In Vivo: BMS-906024 (8.5 mg/kg; oral gavage; days 1 through 4 of each week for 3 weeks) significantly enhances the tumor growth inhibition of Paclitaxel (36 mg/kg). BMS-906024 enhances Paclitaxel-mediated cytotoxicity in vivo in NSCLC through a combination of inhibiting proliferation and promoting apoptosis, in a p21 and p57-independent manner^[1].
BMS-906024 has a T_1/2 of 4.6/5.3 hours, a C_max of 1/0.3 μM and an AUC of 3.4/1.9 μM?hour for IV/PO^[2].