1369665-02-0
1369665-02-0 structure
- Name: Cobimetinib (hemifumarate)
- Chemical Name: (E)-but-2-enedioic acid,[3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-[3-hydroxy-3-[(2S)-piperidin-2-yl]azetidin-1-yl]methanone
- CAS Number: 1369665-02-0
- Molecular Formula: C25H25F3IN3O6
- Molecular Weight: 647.38200
- Catalog: Research Areas Cancer
- Create Date: 2018-10-17 08:57:45
- Modify Date: 2024-01-02 18:10:17
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Cobimetinib hemifumarate is a novel selective MEK inhibitor, and the IC50 value against MEK1 is 4.2 nM.
| Name | (E)-but-2-enedioic acid,[3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-[3-hydroxy-3-[(2S)-piperidin-2-yl]azetidin-1-yl]methanone |
|---|---|
| Synonyms |
UNII-6EXI96H8SV
Cobimetinib hemifumarate Xl-518 hemifumarate Methanone,(3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)phenyl)(3-hydroxy-3-(2S)-2-piperidinyl-1-azetidinyl)-,(2E)-2-butenedioate (2:1) GDC-0973 hemifumarate Cobimetinib Fumarate Cobimetinib (hemifumarate) |
| Description | Cobimetinib hemifumarate is a novel selective MEK inhibitor, and the IC50 value against MEK1 is 4.2 nM. |
|---|---|
| Related Catalog | |
| Target |
MEK1:4.2 nM (IC50) |
| 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)[1]. Mitochondrial OXPHOS limits cell death induced by cobimetinib (100 nM) in melanoma with constitutive MAPK activation in A375 cells[4]. |
| 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[1]. 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[2]. 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)[3]. |
| Animal Admin | 5 million WM-266-4 melanoma cells are resuspended in Hank balanced salt solution and implanted intradermally into the hind flank of female NCR nude mice. On days 11 or 13 after the implantation, xenograft mice with tumor volumes of approximately 100 to 120 mm3 are randomLy assigned to 8 groups (n=27 per group), 4 single dose groups and 4 multiple dose groups. One day after randomization and group assignment, mice in the single dose groups are given a single oral dose of vehicle (water for injection USP), 1, 3, or 10 mg/kg of Cobimetinib (GDC-0973, expressed as free base equivalents). Mice in the multiple dose groups are given daily oral doses of vehicle (water for injection USP), 1, 3, or 10 mg/kg of GDC-0973 for 14 days. Plasma and tumor samples (n=3 per time point) are collected from euthanized mice predose and at 2, 4, 8, 16, 24, 72, 120, and 168 hours postdose on day 1 (single dose groups) or day 14 (multiple dose groups). Samples are stored at −80°C until analysis. GDC-0973 concentrations in plasma and tumor lysates are determined using liquid chromatography/tandem mass spectrometry (LC/MS-MS). The dynamic range of the assay is 0.004 to 35 μM. |
| References |
| Molecular Formula | C25H25F3IN3O6 |
|---|---|
| Molecular Weight | 647.38200 |
| Exact Mass | 647.07400 |
| PSA | 139.20000 |
| LogP | 3.83260 |
| Storage condition | 2-8℃ |