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JH-X-119-01

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Chemical Structure| 2227368-54-7 同义名 : -
CAS号 : 2227368-54-7
货号 : A1487545
分子式 : C25H20N6O3
纯度 : 99%+
分子量 : 452.465
MDL号 : MFCD34593626
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 120 mg/mL(265.21 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Jh-X-119-01 is a highly potent and selective covalent inhibitor of IRAK1. JH-X-119-01 inhibited IRAK1 biochemically with an IC50 of 9.3 nM while exhibiting no inhibition of IRAK4 at concentrations up to 10 µM, and showed exceptional Kinome selectivity with off-target inhibition of only two kinases, YSK4 and MEK3. Intact protein MS labeling studies confirmed that JH-X-119-01 irreversibly labels IRAK1 at C302. Jh-X-119-01 exhibited cytotoxic activity at single digit micromolar concentrations in a panel of WM (Waldenström's macroglobulinemia), DLBCL (Diffused Large B-cell Lymphoma), and lymphoma cell lines expressing MYD88. Cotreatment of JH-X-119-01 with the BTK inhibitor ibrutinib resulted in synergistic killing effects in these systems. Importantly, the combination of JH-X-119-01 with Ibrutinib led to synergistic tumor cell killing in MYD88 mutated WM and ABC-DLBCL cells, and suppression of NF-ĸB activation. JH-X-119-01 shows synergistic tumor cell killing with ibrutinib in MYD88 mutated WM and ABC-DLBCL cells. In vivo PK studies revealed a favorable profile for JH-X-119-01 with a moderate half-life of 1.61 hours, a Cmax of 9.95 µM, and a low clearance of 18.84 mL/min/kg when dosed IV[1].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.21mL

0.44mL

0.22mL

11.05mL

2.21mL

1.11mL

22.10mL

4.42mL

2.21mL
参考文献

[1]Hatcher JM, Yang G, Wang L, Ficarro SB, Buhrlage S, Wu H, Marto JA, Treon SP, Gray NS. Discovery of a Selective, Covalent IRAK1 Inhibitor with Antiproliferative Activity in MYD88 Mutated B-Cell Lymphoma. ACS Med Chem Lett. 2020 Oct 9;11(11):2238-2243