Nemtabrutinib (ARQ 531)

製品コードS8711 バッチS871101

化学情報

	Synonyms	MK-1026	Storage (From the date of receipt)	3 years -20°C powder
	化学式	C₂₅H₂₃ClN₄O₄
	分子量	478.93	CAS No.	2095393-15-8
Solubility (25°C)*	体外	DMSO	95 mg/mL (198.35 mM)
		Ethanol	7 mg/mL (14.61 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	Nemtabrutinib (ARQ 531, MK-1026) is an ATP-competitive tyrosine kinase inhibitor designed to target BTK with an IC50 of 0.85 nM. It also has a distinct kinase selectivity profile with strong inhibitory activity against several key oncogenic drivers from TEC, Trk and Src family kinases.
in vitro	ARQ 531 potently inhibited BTK (IC50 = 0.85 nM), the binding potency was accompanied by long residence time (51 min). ARQ 531 selectively inhibits BCR signaling dependent PI3K/AKT/mTOR, Ras/Raf/Erk and Rap-GTPase-Cofilin pathways in TMD8 cells. It potently inhibits proliferation of hematological malignant cell lines both sensitive and resistant to ibrutinib addicted to BCR signaling^[1]. Unlike ibrutinib, ARQ 531 suppressed both the upstream activating signals (via inhibition of a select member of Src kinase family) and the downstream signaling pathways (via pAKT and pERK kinases). In GCB-DLBCL cell lines (SUDHL-4 and DOHH-2), ARQ 531 potently suppressed expression of anti-apoptotic c-Myc and BCL6 oncoproteins in a dose dependent fashion, and concomitantly induced apoptotic cleavage of PARP protein^[2].
in vivo	ARQ 531 has potent anti-tumor activity was observed in both ABC-DLBCL and GCB-DLBCL mouse xenograft models^[1]. ARQ 531 crosses the blood, brain-barrier^[2]. In a single oral dose study of 10mg/kg in monkeys, the bioavailability of ARQ 531 is 72.4% with a Cmax of 9 μM and a half-life greater than 24 hours^[3].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	CLL cells
	濃度	0.1 μM, 1.0 μM, or 10.0 μM
	反応時間	72 h
	実験の流れ	--
動物実験	動物モデル	B6 mice engrafted with 1E7 CD5+/CD19+ TCL1 lymphocytes via tail vein injection
	投薬量	50 or 75 mg/kg
	投与方法	by oral gavage

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：

BTK inhibition sensitizes Acute Lymphoblastic Leukemia to asparaginase by suppressing the Amino Acid Response pathway [ Blood, 2021, blood.2021011787]	PubMed: 34280258

BTK inhibition sensitizes Acute Lymphoblastic Leukemia to asparaginase by suppressing the Amino Acid Response pathway [ Blood, 2021, blood.2021011787]

PubMed: 34280258

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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