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GSK2982772

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Chemical Structure| 1622848-92-3 同义名 : -
CAS号 : 1622848-92-3
货号 : A363017
分子式 : C20H19N5O3
纯度 : 99%+
分子量 : 377.397
MDL号 : MFCD30828708
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 250 mg/mL(662.43 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
靶点

  • TNF-α

    human RIP1, IC50:16 nM
描述 GSK2982772 is an optimized RIP1 kinase inhibitor with IC50 value of 1nM in a FP/ADP-Glo assay, which is a clinical candidate currently in phase 2a clinical studies for psoriasis, rheumatoid arthritis, and ulcerative colitis. It inhibited U937 cell viability with IC50 value of 6.3nM. Treatment with GSK2982772 at 300nM overnight reduced IL-1β and IL-6 production by ~60% in human explant samples taken from ulcerative colitis patients. GSK2982772 dosed orally 15 min prior to TNF and showed 68, 80 and 87% protection from temperature loss over 6 h, at doses of 3, 10, and 50 mg/kg, respectively. It showed 13, 63, and 93% protection from temperature loss over 3h in the corresponding TNF/zVAD model[2].
作用机制 GSK2982772 packed against 2 β-strands defined by Leu90-Val91-Met92 and Ile43-Met44-Lys45 of RIP1 kinase, siting deeper in the ATP binding pocket and occupying an allosteric lipophilic pocket at the back through the benzyl group.[2]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.65mL

0.53mL

0.26mL

13.25mL

2.65mL

1.32mL

26.50mL

5.30mL

2.65mL
参考文献

[1]Harris PA, Berger SB, et al. Discovery of a First-in-Class Receptor Interacting Protein 1 (RIP1) Kinase Specific Clinical Candidate (GSK2982772) for the Treatment of Inflammatory Diseases. J Med Chem. 2017 Feb 23;60(4):1247-1261.

[2]Harris PA, Berger SB, Jeong JU, Nagilla R, Bandyopadhyay D, Campobasso N, Capriotti CA, Cox JA, Dare L, Dong X, Eidam PM, Finger JN, Hoffman SJ, Kang J, Kasparcova V, King BW, Lehr R, Lan Y, Leister LK, Lich JD, MacDonald TT, Miller NA, Ouellette MT, Pao CS, Rahman A, Reilly MA, Rendina AR, Rivera EJ, Schaeffer MC, Sehon CA, Singhaus RR, Sun HH, Swift BA, Totoritis RD, Vossenkämper A, Ward P, Wisnoski DD, Zhang D, Marquis RW, Gough PJ, Bertin J. Discovery of a First-in-Class Receptor Interacting Protein 1 (RIP1) Kinase Specific Clinical Candidate (GSK2982772) for the Treatment of Inflammatory Diseases. J Med Chem. 2017 Feb 23;60(4):1247-1261. doi: 10.1021/acs.jmedchem.6b01751. Epub 2017 Feb 10. PMID: 28151659.