|2-((S)-4-(7-(8-氯萘-1-基)-2-(((S)-1-甲基吡咯烷-2-基)甲氧基)-5,6,7,8-四氢吡啶并[3,4-d]嘧啶-4-基)-1-(2-氟丙烯酰基)哌嗪-2-基)乙腈|CsnPharm

CAS No.: 2326521-71-3

Adagrasib Catalog No. CSN25249

Synonyms: MRTX849

MRTX849 is a potent, selective and covalent K-Ras (G12C) inhibitor that exhibits favorable drug-like properties, selectively modifies mutant cysteine 12 in GDP-bound K-Ras (G12C), and inhibits KRAS-dependent signaling.

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400-920-2911

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tech@csnpharm.cn

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技术信息

生物活性

描述KRAS is one of the most frequently mutated oncogenes in cancer. KRAS^G12C mutations are present in lung and colon adenocarcinoma as well as smaller fractions of other cancers. MRTX849 is a potent, selective, and covalent KRAS^G12C inhibitor. MRTX849 demonstrated much greater modification of KRAS^G12C when preloaded with GDP compared with GTP supporting that MRTX849 binds to and stabilizes the inactive GDP-bound form of KRAS^G12C. In the KRAS^G12C-mutant H358 lung and MIA PaCa-2 pancreatic cancer cell lines, MRTX849 demonstrated an upward electrophoretic mobility shift of KRAS^G12C protein band migration by immunoblot, indicative of covalent modification of KRAS^G12C. MRTX849 potently inhibited cell growth in the vast majority of KRAS^G12C-mutant cell lines with IC₅₀ values ranging between 10 and 973 nM in the 2D format and between 0.2 and 1042 nM in the 3D format. In vivo, the modified fraction of KRAS^G12C was 74% at 6 hours post-dose and gradually decreased to 47% by 72 hours after a single oral dose of MRTX849 at 30 mg/kg to H358 xenograft-bearing mice. To evaluate the effect of MRTX849 on KRAS-dependent signal transduction in vivo, a single dose of MRTX849 at 10, 30 or 100 mg/kg was administered to H358 tumor-bearing mice. Dose-dependent inhibition of ERK1/2 and pS6^S235/36 phosphorylation was observed at 6 hours post-dose. Finally, significant, dose-dependent, anti-tumor activity was observed at the 3, 10, 30 and 100 mg/kg dose levels of MRTX849 in the MIA PaCa-2 model^[1].
参考文献

[1] Hallin J, Engstrom LD, Hargis L, et al. The KRAS^G12C Inhibitor MRTX849 Provides Insight toward Therapeutic Susceptibility of KRAS-Mutant Cancers in Mouse Models and Patients. Cancer Discov. 2020;10(1):54-71

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 1.6553 mL
- 8.2765 mL
- 16.5531 mL
- 5 mM
- 0.3311 mL
- 1.6553 mL
- 3.3106 mL
- 10 mM
- 0.1655 mL
- 0.8277 mL
- 1.6553 mL

技术信息

CAS号

2326521-71-3

储存条件

粉末: Sealed in dry,2-8°C

液体: -20°C:3-6 月 -80°C:12月

分子式

C32H35ClFN7O2

运输

蓝冰

分子量

604.12

别名

MRTX849

溶解度

DMSO	100.0 mg/mL (165.5 mM)
Water	Insoluble
Ethanol	50.0 mg/mL (82.8 mM)

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