Description: 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.For research use only. We do not sell to patients. Molecular Weight 556.50 Appearance Solid Formula C26H26F6N4O3 CAS No. 1401066-79-2 SMILES O=C(N[C@@H]1C(N(C)C2=CC=CC=C2C(C3=CC=CC=C3)=N1)=O)[C@H](CCC(F)(F)F)[C@H](CCC(F)(F)F)C(N)=O Shipping Room temperature in continental US; may vary elsewhere. Storage Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month IC50 & Target: IC50: 1.6 nM (Notch1), 0.7 nM (Notch2), 3.4 nM (Notch3) and 2.9 nM (Notch4) 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]. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot Analysis Cell Line: NSCLC cell lines (A549, H358, H1975, H2444, H1792, HCC44) Concentration: 5, 10, 25, 50, 100 nM Incubation Time: 72 hours Result: Reduced Notch1 ICD levels in all six lung cancer cell lines tested at concentrations as low as 5 nM, with maximal depletion at 50-100 nM. 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 T1/2 of 4.6/5.3 hours, a Cmax of 1/0.3 μM and an AUC of 3.4/1.9 μM•hour for IV/PO[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Six to 12-week-old female NOD scid gamma (NSG) mice with KRAS- and BRAF-WT PDX-T42 xenografts[1] Dosage: 8.5 mg/kg Administration: oral gavage; days 1 through 4 of each week for 3 weeks Result: Significantly enhanced the tumor growth inhibition of Paclitaxel (36 mg/kg), but had no significant effect on Cisplatin (2 mg/kg) treatment. Clinical Trial: NCT Number Sponsor Condition Start Date Phase NCT01363817 Bristol-Myers Squibb Lymphoblastic Leukemia, Acute T-cell|Precursor T-Cell Lymphoblastic Lymphoma September 28, 2011 Phase 1 NCT01653470 Bristol-Myers Squibb Cancer October 12, 2012 Phase 1 NCT01292655 Bristol-Myers Squibb Cancer March 3, 2011 Phase 1 Disclaimer: For laboratory research use only.
