Adagrasib (MRTX849)

製品コードS8884 バッチS888406

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

To evaluate the breadth of activity of Adagrasib (MRTX849), 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. It 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.[1].
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 exhibits 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 remains tumor-free through study Day 70.[1].

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 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
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
SRC kinase drives multidrug resistance induced by KRAS-G12C inhibition [ Sci Adv, 2024, 10(50):eadq4274] PubMed: 39661665
ADT-1004: A First-in-Class, Orally Bioavailable Selective pan-RAS Inhibitor for Pancreatic Ductal Adenocarcinoma [ bioRxiv, 2024, 2024.10.04.616725] PubMed: 39416034

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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