Naporafenib (LXH254)

製品コードS8745 バッチS874501

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder
	化学式	C₂₅H₂₅F₃N₄O₄
	分子量	502.49	CAS No.	1800398-38-2
Solubility (25°C)*	体外	DMSO	100 mg/mL (199.0 mM)
		Ethanol	34 mg/mL (67.66 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	Naporafenib (LXH254) is a type II ATP-competitive inhibitor that inhibits both B- and CRAF kinase activities at picomolar concentrations with a high degree of selectivity against a panel of 456 human kinases and in cell-based assays.
in vitro	LXH254 not only inhibits MAPK signaling activity in tumor models harboring BRAFV600 mutation, but also inhibits mutant N- and KRAS-driven signaling due to its ability to inhibit both RAF monomers and dimers with similar potencies. LXH254 is orally bioavailable, demonstrates a direct PK/PD relationship and causes tumor regression in multiple cell line and primary human tumor derived xenograft models at well-tolerated doses^[1].

製品説明

Naporafenib (LXH254) is a type II ATP-competitive inhibitor that inhibits both B- and CRAF kinase activities at picomolar concentrations with a high degree of selectivity against a panel of 456 human kinases and in cell-based assays.

in vitro

LXH254 not only inhibits MAPK signaling activity in tumor models harboring BRAFV600 mutation, but also inhibits mutant N- and KRAS-driven signaling due to its ability to inhibit both RAF monomers and dimers with similar potencies. LXH254 is orally bioavailable, demonstrates a direct PK/PD relationship and causes tumor regression in multiple cell line and primary human tumor derived xenograft models at well-tolerated doses^[1].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	Ku-19-19 cells
	濃度	2 μM
	反応時間	3 days
	実験の流れ	For crystal violet staining experiments, cells were seeded in 6-well plates at 50,000 to 100,000 cells/well for 3-day experiments and vehicle or drug (diluted in media) was added the day after plating.
動物実験	動物モデル	Female athymic nude mice
	投薬量	30 mg/kg
	投与方法	i.p.

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：

BRAFΔβ3-αC in-frame deletion mutants differ in their dimerization propensity, HSP90 dependence, and druggability [ Sci Adv, 2023, 9(35):eade7486]	PubMed: 37656784
RAF1 amplification drives a subset of bladder tumors and confers sensitivity to MAPK-directed therapeutics [ J Clin Invest, 2021, e147849]	PubMed: 34554931
RAF1 amplification drives a subset of bladder tumors and confers sensitivity to MAPK-directed therapeutics [ J Clin Invest, 2021, e147849]	PubMed: 34554931
Pan-RAF inhibitor LY3009120 is highly synergistic with low-dose cytarabine, but not azacitidine, in acute myeloid leukemia with RAS mutations [ Oncol Lett, 2021, 22(5):745]	PubMed: 34539849
Durable Suppression of Acquired MEK Inhibitor Resistance in Cancer by Sequestering MEK from ERK and Promoting Anti-Tumor T-cell Immunity [ Cancer Discov, 2020, CD-20-0873]	PubMed: 33318037
Combined blockade of polo-like kinase and pan-RAF is effective against NRAS-mutant non-small cell lung cancer cells [ Cancer Lett, 2020, 495:135-144]	PubMed: 32979462

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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