Cobimetinib hemifumarate - CAS# 1369665-02-0

Cobimetinib hemifumarate is a novel selective MEK1 inhibitor, and the IC50 value against MEK1 is 4.2 nM.

Product information

CAS Number: 1369665-02-0

Molecular Weight: 1178.69

Formula: C46H46F6I2N6O8

Chemical Name: (S)-(3, 4-difluoro-2-((2-fluoro-4-iodophenyl)amino)phenyl)(3-hydroxy-3-(piperidin-2-yl)azetidin-1-yl)methanone hemifumarate

Smiles: OC1(CN(C1)C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F)[C@@H]1CCCCN1.OC1(CN(C1)C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F)[C@@H]1CCCCN1.OC(=O)/C=C/C(O)=O

InChiKey: RESIMIUSNACMNW-BXRWSSRYSA-N

InChi: InChI=1S/2C21H21F3IN3O2.C4H4O4/c2*22-14-6-5-13(19(18(14)24)27-16-7-4-12(25)9-15(16)23)20(29)28-10-21(30,11-28)17-3-1-2-8-26-17;5-3(6)1-2-4(7)8/h2*4-7,9,17,26-27,30H,1-3,8,10-11H2;1-2H,(H,5,6)(H,7,8)/b;;2-1+/t2*17-;/m00./s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 50 mg/mL (84.85 mM; Need ultrasonic). H2O : < 0.1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

The EC50 values of Cobimetinib (GDC-0973) for 888MEL and A2058 cells are 0.2 μM, 10 μM, respectivelly. Melanoma cells are treated with EC50 concentration of MEK and PI3K inhibitors for 24 hours (888MEL: 0.05 μM GDC-0973, 2.5 μM GDC-0941; A2058: 2.5 μM GDC-0973, 2.5 μM GDC-0941). Mitochondrial OXPHOS limits cell death induced by cobimetinib (100 nM) in melanoma with constitutive MAPK activation in A375 cells.

In Vivo:

In the NCI-H2122 KRASG12C mutant non-small cell lung carcinoma (NSCLC) xenograft model, treatment with up to 5 mg/kg Cobimetinib (GDC-0973) lead to moderate TGI and at 10 mg/kg approaches tumor stasis. GDC-0973 and GDC-0941 are administered to A2058 tumor-bearing mice daily (QD) or every third day (Q3D) either as single agents or in combination. The population rate constants associated with tumor growth inhibition for GDC-0973 and GDC-0941 are 0.00102 and 0000651 μM-1 h-1, respectively. Following single doses of GDC-0973 (1, 3, or 10 mg/kg, p.o.) estimated in vivo IC50 values of %pERK decrease based on tumor concentrations in xenograft mice are 0.78 (WM-266-4) and 0.52 μM (A375).

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