Adagrasib (MRTX849)

製品コードS8884 バッチS888403

化学情報

	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)
		Water	Insoluble
		Ethanol	Insoluble
* <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 MRTX849 activity, its effect on cell viability is determined across a panel of 17 KRAS^G12C-mutant and three non-KRAS^G12C-mutant cancer cell lines using 2D (3-day, adherent cells) and 3D (12-day, spheroids) cell growth conditions. MRTX849 potently inhibits cell growth in the vast majority of KRAS^G12C-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. CellTiter-Glo assay to evaluate cell viability performed on seven KRAS G12C-mutant cell lines and three non-KRAS G12C-mutant cell lines cells grown in 2D tissue culture conditions in a 3-day assay or 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

[1] Jill Hallin,et al.Cancer Discov.2020;10 (1): 54-71.

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：

AXL signal mediates adaptive resistance to KRAS G12C inhibitors in KRAS G12C-mutant tumor cells [ Cancer Lett, 2024, 587:216692]	PubMed: 38342232
Anticancer Efficacy of KRASG12C Inhibitors Is Potentiated by PAK4 Inhibitor KPT9274 in Preclinical Models of KRASG12C-Mutant Pancreatic and Lung Cancers [ Mol Cancer Ther, 2023, 22(12):1422-1433]	PubMed: 37703579
Targeted therapies prime oncogene-driven lung cancers for macrophage-mediated destruction [ bioRxiv, 2023, 2023.03.03.531059]	PubMed: 36945559
Creating MHC-restricted neoantigens with covalent inhibitors that can be targeted by immune therapy [ Cancer Discov, 2022, CD-22-1074]	PubMed: 36250888
Integrated analysis of the tumor microenvironment using a reconfigurable microfluidic cell culture platform [ FASEB J, 2022, 36(10):e22540]	PubMed: 36083096
Development of a biotin-streptavidin-enhanced enzyme-linked immunosorbent assay (BA-ELISA) for high-throughput screening of KRASG12C inhibitors [ SLAS Discov, 2022, 27(2):107-113]	PubMed: 35058184
Profiling oncogenic KRAS mutant drugs with a cell-based Lumit p-ERK immunoassay [ SLAS Discov, 2022, S2472-5552(22)12517-7]	PubMed: 35288294
Inhibitor of the Nuclear Transport Protein XPO1 Enhances the Anticancer Efficacy of KRAS G12C Inhibitors in Preclinical Models of KRAS G12C-Mutant Cancers [ Cancer Res Commun, 2022, 2(5):342-352]	PubMed: 35573474
Clinical Acquired Resistance to KRASG12C Inhibition through a Novel KRAS Switch-II Pocket Mutation and Polyclonal Alterations Converging on RAS-MAPK Reactivation [ Cancer Discov, 2021, 11(8):1913-1922]	PubMed: 33824136
Lentiviral-driven discovery of cancer drug resistance mutations [ Cancer Res, 2021, canres.1153.2021]	PubMed: 34301758

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。