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GSK2983559 free acid

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Chemical Structure| 1579965-12-0 同义名 : GSK2983559;compound 3;RIPK2-IN-1;RIP2 kinase inhibitor 1
CAS号 : 1579965-12-0
货号 : A939659
分子式 : C21H23N4O7PS2
纯度 : 99%+
分子量 : 538.534
MDL号 : MFCD30489430
存储条件：

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 4 mg/mL(7.43 mM)，配合低频超声，并水浴加热至45℃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 Receptor-interacting-protein kinase 2 (RIP2) has been identified as a key signal transduction partner in the nucleotide oligomerization domain 2 (NOD2) pathway contributing to a variety of human pathologies, including immune-mediated inflammatory diseases. GSK2983559 is the first RIP2 kinase inhibitor to enter clinical trials, currently under phase 1 evaluation. VEGFR3 was the only kinase inhibited by more than 90% by GSK2983559. An additional 11 kinases were inhibited in the range of 70−89%. In a screen against non-kinase targets (Eurofins, 104 receptor and ion channel binding assays and 35 enzyme and cell-based assays), GSK2983559 was highly selective, inhibiting only melatonin receptor MT3 at a concentration under 10 μM. The in vivo efficacy of GSK2983559 was evaluated in a murine 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced colitis model. Mice were dosed orally from days −2 to 5 at 0.25, 7.5, and 145 mg/kg b.i.d. which corresponds to predicted 10%, 50%, and 90% inhibition at 24 h, respectively. Further, administration of GSK2983559 at the 7.5 and 145 mg/kg b.i.d. doses exhibited efficacy similar to that of prednisolone as measured by summed colon scores[1].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.86mL

0.37mL

0.19mL

9.28mL

1.86mL

0.93mL

18.57mL

3.71mL

1.86mL
参考文献

[1]Haile PA, Casillas LN, Votta BJ, et al. Discovery of a First-in-Class Receptor Interacting Protein 2 (RIP2) Kinase Specific Clinical Candidate, 2-((4-(Benzo[d]thiazol-5-ylamino)-6-(tert-butylsulfonyl)quinazolin-7-yl)oxy)ethyl Dihydrogen Phosphate, for the Treatment of Inflammatory Diseases. J Med Chem. 2019;62(14):6482-6494