| CAS |
No.1622848-92-3 |
| 英文名称 |
GSK2982772 |
| 别名 |
;GSK2982772;GSK-2982772;GSK2982772.;(2S，5R，;DicloxacillinS |
| 分子式 |
C10H20N2O2 |
| 分子量 |
200.28 |
| 溶解性 |
Soluble in DMSO |
| 纯度 |
≥98% |
| 外观(性状) |
White to yellow Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| 运输条件 |
冷藏运输 |
| MDL |
MFCD30828708 |
| SMILES |
O=C(C1=NC(CC2=CC=CC=C2)=NN1)N[C@H]3COC4=CC=CC=C4N(C)C3=O |
| 靶点 |
RIP kinase |
| 通路 |
Apoptosis |
| 背景说明 |
GSK2982772是receptor-interacting protein-1 (RIP1) kinase (RIPK1)的ATP竞争性抑制剂。 |
| 生物活性 |
GSK2982772 is a potent， orally active and ATP competitive RIP1 kinase inhibitor with IC50 values of 16 nM and 20 nM for human and monkey RIP1， respectively.[1] |
| IC50 |
IC50: 16 nM (human RIP1 FP)IC50: 20 nM (monkey RIP1 FP)IC50: 2 μM (rat RIP1 FP)IC50: 2.5 μM (mouse RIP1 FP)[1] |
| In Vitro |
GSK2982772 shows more than 1，000-fold selectivity for ERK5 over a panel of over 339 kinases at 10 μM. In stimulated cellular systems，GSK2982772 is also able to reduce spontaneous production of cytokines (IL-1β and IL-6) in a concentration-dependent fashion from ulcerative colitis explant tissue in overnight incubations. GSK2982772 produces a weak concentration dependent inhibition of hERG in human embryonic kidney (HEK-293) cells， with an estimated IC50 of 195 μM， and also shows a weak activation of the human Pregnane X receptor (hPXR) with an EC50 of 13 μM[1]. |
| In Vivo |
GSK2982772 is dosed orally 15 min prior to TNF and shows 68， 80， and 87% protection from temperature loss over 6 h， at doses of 3， 10， and 50 mg/kg， respectively. In the corresponding TNF/zVAD model， GSK2982772 shows 13， 63， and 93% protection from temperature loss over 3 h. GSK2982772 displays a good free fraction in blood in rats (4.2%)， dogs (11%)， cynomolgus monkeys (11%)， and humans (7.4%). The inhibitor has a good pharmacokinetic profile across both rats and monkeys. GSK2982772 distributes into a range of tissues including the colon， liver， kidney， and heart at concentrations comparable to those of blood. However， GSK2982772 has low brain penetration in rat (4%) despite possessing good cell permeability (21×10-6 cm/s)[1]. |
| 动物实验 |
Mice: A total of 7 mice per dose group are orally predosed with saline or GSK2982772 at doses of 3， 10， and 50 mg/kg 15 min before i.v. administration of mouse TNF (30 μg/ mouse). Temperature loss in the mice is measured by a rectal probe. The study is terminated after 6 h when the control group lost 7 °C[1]. |
| 数据来源文献 |
[1]. Harris PA， 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. |
| 规格 |
1mg 5mg 10mg |
| 单位 |
瓶 |
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