Adagrasib (MRTX849)

製品コードS8884 バッチS888401

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)
		Ethanol	50 mg/mL (82.76 mM)
		Water	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：

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
AXL signal mediates adaptive resistance to KRAS G12C inhibitors in KRAS G12C-mutant tumor cells [ Cancer Lett, 2024, 587:216692]	PubMed: 38342232
ADT-1004: A First-in-Class, Orally Bioavailable Selective pan-RAS Inhibitor for Pancreatic Ductal Adenocarcinoma [ bioRxiv, 2024, 2024.10.04.616725]	PubMed: 39416034
Blocking Genomic Instability Prevents Acquired Resistance to MAPK Inhibitor Therapy in Melanoma [ Cancer Discov, 2023, 13(4):880-909]	PubMed: 36700848
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

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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