Adagrasib (MRTX849)

製品コードS8884 バッチS888402

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
化学式

C32H35ClFN7O2
分子量 604.12 CAS No. 2326521-71-3
Solubility (25°C)* 体外 DMSO 100 mg/mL (165.53 mM)
Ethanol 100 mg/mL (165.53 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Adagrasib (MRTX849)は、強力かつ選択的共有結合性のKRAS G12C阻害剤であり、良好な薬剤様特性を示し、GDP結合型KRAS G12Cの変異型システイン12を選択的に修飾し、KRAS依存性シグナル伝達を阻害します。
in vitro

To evaluate the breadth of Adagrasib (MRTX849) activity, its effect on cell viability is determined across a panel of 17 KRASG12C-mutant and three non-KRASG12C-mutant cancer cell lines using 2D (3-day, adherent cells) and 3D (12-day, spheroids) cell growth conditions. This compound potently inhibits cell growth in the vast majority of KRASG12C-mutant cell lines with IC50 values ranging between 10 nM and 973 nM in the 2D format and between 0.2 nM and 1042 nM in the 3D format..
in vivo

Rapid tumor regression is observed at the earliest posttreatment tumor measurement and animals in the 30 mg/kg and 100 mg/kg cohorts of Adagrasib (MRTX849) exhibit evidence of a complete response at study Day 15. Dosing is stopped at study Day 16 and all 4 mice in the 100 mg/kg cohort and 2 out of 7 mice in the 30 mg/kg cohort remain tumor-free through study Day 70..

プロトコル(参考用のみ)

細胞アッセイ 細胞株 MIA PaCa-2, H1373, H358, H2122, SW1573, H2030, KYSE-410 cells (G12C); H1299 (WT); A549 (G12S), HCT116 (G13D) cells
濃度 --
反応時間 24 h
実験の流れ

All cell lines were maintained at 37 ℃ in a humidified incubator at 5% CO2 and were periodically checked for mycoplasma. A CellTiter-Glo assay to evaluate the effect of Adagrasib (MRTX849) on cell viability was performed on seven KRAS G12C-mutant cell lines and three non-KRAS G12C-mutant cell lines, grown in 2D tissue culture conditions in a 3-day assay or in 3D conditions using 96-well, ULA plates in a 12-day assay.
動物実験 動物モデル MIA PaCa-2 model
投薬量 3 mg/kg, 10 mg/kg, 30 mg/kg and 100 mg/kg
投与方法 Oral gavage

参考

  • https://pubmed.ncbi.nlm.nih.gov/31658955-the-kras-g12c-inhibitor-mrtx849-provides-insight-toward-therapeutic-susceptibility-of-kras-mutant-cancers-in-mouse-models-and-patients/?from_single_result=The+KRASG12C+Inhibitor%2C+MRTX849%2C+Provides+Insight+Toward+Therapeutic+Susceptibility+of+KRAS+Mutant+Cancers+in+Mouse+Models+and+Patients

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Systemic activation of NRF2 contributes to the therapeutic efficacy of clinically-approved KRAS-G12C anti-cancer drugs [ Br J Cancer, 2025, 10.1038/s41416-025-03162-7] PubMed: 40890297
Single-molecule imaging quantifies oncogenic KRAS dynamics for enhanced accuracy of therapeutic efficacy assessment [ iScience, 2025, 28(9):113374] PubMed: 40949096
Activity of direct KRAS(G12C) inhibitors in preclinical models of pediatric cancer [ Mol Cancer Ther, 2025, 10.1158/1535-7163.MCT-25-0022] PubMed: 41340466
Quantifying small GTPase activation status using a novel fluorescence HPLC-based assay [ J Biol Chem, 2025, 301(6):108545] PubMed: 40286847
LC-MS/MS method development and validation for novel targeted anticancer therapies adagrasib, capmatinib, ensartinib, entrectinib, larotrectinib, lorlatinib, pralsetinib, selpercatinib and sotorasib [ J Pharm Biomed Anal, 2025, 266:117078] PubMed: 40743983
Base editing screens define the genetic landscape of cancer drug resistance mechanisms [ Nat Genet, 2024, 10.1038/s41588-024-01948-8] PubMed: 39424923
Combined inhibition of KRASG12C and mTORC1 kinase is synergistic in non-small cell lung cancer [ Nat Commun, 2024, 15(1):6076] PubMed: 39025835
Targeted therapies prime oncogene-driven lung cancers for macrophage-mediated destruction [ J Clin Invest, 2024, 134(9)e169315] PubMed: 38483480
AXL signal mediates adaptive resistance to KRAS G12C inhibitors in KRAS G12C-mutant tumor cells [ Cancer Lett, 2024, 587:216692] PubMed: 38342232
WEE1 confers resistance to KRASG12C inhibitors in non-small cell lung cancer [ Cancer Lett, 2024, 611:217414] PubMed: 39725152

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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