ChemicalBook CAS DataBase List 1401066-79-2

1401066-79-2

Name	BMS-906024
CAS	1401066-79-2
Molecular Formula	C26H26F6N4O3
MDL Number	MFCD24849414
Molecular Weight	556.5
MOL File	1401066-79-2.mol

Chemical Properties

storage temp.	Store at -20°C
solubility	Soluble in DMSO
form	Solid
color	White to off-white

Safety Data

Symbol(GHS)	GHS07
Signal word	Warning
Hazard statements	H302-H315-H319-H335
Precautionary statements	P261-P305+P351+P338

Hazard Information

Uses

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].

Definition

ChEBI: (2S,3R)-N'-[(3S)-1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]-2,3-bis(3,3,3-trifluoropropyl)butanediamide is a primary carboxamide, a secondary carboxamide and a tertiary carboxamide.

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].

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.

Animal Model:	Mouse^[2]
Dosage:	1 mg/kg (Pharmacokinetic Analysis)
Administration:	IV or PO
Result:	Had 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.

References

[1] Morgan KM, et al. Gamma Secretase Inhibition by BMS-906024 Enhances Efficacy of Paclitaxel in Lung Adenocarcinoma. Mol Cancer Ther. 2017 Dec;16(12):2759-2769. DOI:10.1158/1535-7163.MCT-17-0439
[2] Gavai AV, et al. Discovery of Clinical Candidate BMS-906024: A Potent Pan-Notch Inhibitor for the Treatment of Leukemia and Solid Tumors. ACS Med Chem Lett. 2015 Mar 11;6(5):523-7. DOI:10.1021/acsmedchemlett.5b00001

Spectrum Detail

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