BMS-906024 is a novel, oral and potent pan-Notch inhibitor that demonstrated robust anti-tumor activity at tolerated doses in multiple tumor xenograft models. It is being evaluated in Phase 1 clinical studies. BMS-906024 is being administered IV (once weekly) in the clinic and the projected human efficacious dose is 4 - 6 mg. Based on the preclinical data, the projected human half-life of BMS-906024 is in the 37 h - 124 h range. Deregulation of the Notch pathway has been shown to be oncogenic in numerous tissue types including T-cell acute lymphoblastic leukemia (T-ALL), breast cancer, non-small cell lung cancer, and colorectal carcinoma.

Physicochemical Properties

Molecular Formula	C26H26F4N4O3
Molecular Weight	518.50
Exact Mass	518.194
CAS #	1584713-87-0
PubChem CID	73388374
Appearance	White to off-white solid powder
LogP	4.1
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	9
Heavy Atom Count	37
Complexity	886
Defined Atom Stereocenter Count	3
SMILES	FC(C([H])([H])C([H])([H])[C@@]([H])(C(N([H])[C@]1([H])C(N([H])C2C(=C([H])C([H])=C([H])C=2C(C2C([H])=C([H])C([H])=C([H])C=2[H])=N1)F)=O)=O)[C@@]([H])(C(N([H])[H])=O)C([H])([H])C1([H])C([H])([H])C1([H])[H])(F)F
InChi Key	RANYIWAZSQWERN-WLENULPWSA-N
InChi Code	InChI=1S/C26H26F4N4O3/c27-19-8-4-7-17-20(15-5-2-1-3-6-15)32-23(25(37)33-21(17)19)34-24(36)16(11-12-26(28,29)30)18(22(31)35)13-14-9-10-14/h1-8,14,16,18,23H,9-13H2,(H2,31,35)(H,33,37)(H,34,36)/t16-,18+,23-/m1/s1
Chemical Name	(2R,3S)-3-(cyclopropylmethyl)-N1-((S)-9-fluoro-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-2-(3,3,3-trifluoropropyl)succinamide
Synonyms	BMS-983970; BMS 983970; BMS983970.
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vivo	In solid tumor xenograft models and T-cell acute lymphoblastic leukemia (T-ALL) models, BMS-983970 demonstrates anti-tumor efficacy [1].
References	[1]. Abstract 1643: BMS-983970, an oral pan-Notch inhibitor for the treatment of cancer. Cancer Res October 1, 2014 74; 1643.

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 50 mg/mL (~96.43 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 2.5 mg/mL (4.82 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with heating and sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (4.82 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with heating and sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (4.82 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.9286 mL	9.6432 mL	19.2864 mL
	5 mM	0.3857 mL	1.9286 mL	3.8573 mL
	10 mM	0.1929 mL	0.9643 mL	1.9286 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.