Dabrafenib Mesylate

製品コードS5069 バッチS506904

化学情報

	Synonyms	GSK2118436 Mesylate	Storage (From the date of receipt)	3 years -20°C powder
	化学式	C₂₃H₂₀F₃N₅O₂S₂.CH₄O₃S
	分子量	615.67	CAS No.	1195768-06-9
Solubility (25°C)*	体外	DMSO	100 mg/mL (162.42 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	Dabrafenib Mesylate (GSK2118436) is the mesylate salt form of dabrafenib, an orally bioavailable inhibitor of B-raf (BRAF) protein with IC50s of 0.8 nM, 3.2 nM and 5 nM for B-Raf (V600E), B-Raf (WT) and C-Raf, respectively.
in vitro	Dabrafenib displayed compelling inhibitory activity in enzyme and cellular mechanistic assays, and in cell proliferation assays in B-Raf^V600E-driven melanoma lines, SKMEL28 and A375P F11 (IC50 = 3 and 8 nM, respectively), and colorectal carcinoma line Colo205 (IC50 = 7 nM). Dabrafenib has a minimal effect in vitro on cells with wild-type B-Raf (HFF IC50 = 3.0 μM) and in tumor cells not harboring the activating B-Raf^V600E mutation. It is highly selective, exhibiting >500-fold selectivity for B-Raf^V600E compared to most kinases screened. Significant activity (<100-fold selectivity) was observed for a single kinase in the panel, Alk5. GSK2118436 is significantly less effective at inhibiting SMAD2/3 phosphorylation (IC50 = 3.7 μM) compared with inhibiting ERK phosphorylation (IC50 = 4 nM) in a cellular context^[1]. Cellular inhibition of BRAF^V600E kinase activity by dabrafenib resulted in decreased MEK and ERK phosphorylation and inhibition of cell proliferation through an initial G1 cell cycle arrest, followed by cell death^[2].
in vivo	In a BRAF^V600E-containing xenograft model of human melanoma, orally administered dabrafenib inhibited ERK activation, downregulated Ki67, and upregulated p27, leading to tumor growth inhibition. Dabrafenib is orally bioavailable, doesn’t significantly accumulate after multiple dosing, and causes a reduction of pERK that is sustained for up to 18 h post-dosing after 7 and 14 days of dosing^[2].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	A375P cells
	濃度	8 nM
	反応時間	1 h
	実験の流れ	A375P cells were transfected with the indicated siRNA for 72 h and treated with 8 nM dabrafenib (+) or DMSO control (−) for 1 h. Lysates were immunoblotted.
動物実験	動物モデル	CD1 nu/nu mice bearing A375P F11 (B-Raf^V600E) tumors
	投薬量	0.1, 1, 10, and 100 mg/kg
	投与方法	oral

参考

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：

SB202190 Predicts BRAF-Activating Mutations in Primary Colorectal Cancer Organoids via Erk1-2 Modulation [ Cells, 2023, 12(4)664]	PubMed: 36831331
A modified fluctuation-test framework characterizes the population dynamics and mutation rate of colorectal cancer persister cells [ Nat Genet, 2022, 54(7):976-984]	PubMed: 35817983
Adaptive translational reprogramming of metabolism limits the response to targeted therapy in BRAFV600 melanoma [ Nat Commun, 2022, 13(1):1100]	PubMed: 35232962
Targeting SOX10-deficient cells to reduce the dormant-invasive phenotype state in melanoma [ Nat Commun, 2022, 13(1):1381]	PubMed: 35296667
Candidate therapeutic agents in a newly established triple wild-type mucosal melanoma cell line [ Cancer Commun (Lond), 2022, 42(7):627-647]	PubMed: 35666052
MCU controls melanoma progression through a redox-controlled phenotype switch [ EMBO Rep, 2022, 23(11):e54746]	PubMed: 36156348
Establishment and large-scale validation of a three-dimensional tumor model on an array chip for anticancer drug evaluation [ Front Pharmacol, 2022, 13:1032975]	PubMed: 36313330
Effects of dabrafenib and erlotinib combination treatment on anaplastic thyroid carcinoma [ Endocr Relat Cancer, 2022, 29(6):307-319]	PubMed: 35343921
SERPINB8 and furin regulate ITGAX expression and affect the proliferation and invasion of melanoma cells [ Exp Dermatol, 2022, 10.1111/exd.14677]	PubMed: 36134483
B-Raf inhibitor vemurafenib counteracts sulfur mustard-induced epidermal impairment through MAPK/ERK signaling [ Drug Chem Toxicol, 2022, 1-10]	PubMed: 34986718

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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