Cobimetinib

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Cobimetinib (GDC-0973, XL-518) 是一种有效的选择性 MEK 抑制剂，对 MEK1 的 IC50 为 4.2 nM。

Cobimetinib (GDC-0973, XL-518) is a potent, selective MEK inhibitor with IC50 of 4.2 nM for MEK1; shows excellent selectivity against mTOR, DNA-dependent protein kinase (DNA-PK), and a panel of more than 228 kinases; shows strong cellular potency in a broad panel of tumor types, particularly in BRAF or KRAS mutant cancer cell lines, triggers robust apoptosis and tumor growth inhibition in vivo combined with PI3K inhibitor GDC-0941.Skin Cancer Approved(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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GDC-0973 | XL-518 | GDC 0973 | XL 518 | GDC0973 | XL518

MAPK/ERK Signaling

MEK

MEK1

Cancer

Skin Cancer

934660-93-2

531.31

C21H21F3IN3O2

>98% (HPLC)

10 mM in DMSO

C1CCN[C@@H](C1)C2(CN(C2)C(=O)C3=C(C(=C(C=C3)F)F)NC4=C(C=C(C=C4)I)F)O

Methanone, [3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl][3-hydroxy-3-[(2S)-2-piperidinyl]-1-azetidinyl]-

(-20℃)

With Ice Pack

≥ 2 years