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 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].

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

BMS-906024, Purity: 98.10%