RI-962 是一种有效的选择性受体相互作用蛋白激酶 1
(RIPK1)抑制剂。RI-962 抑制 RIPK1，
IC50值为 35.0 nM。RI-962 可用于神经系统疾病和炎症性疾病的研究。
| 生物活性 |
RI-962 is a potent and selectivereceptor-interacting protein kinase 1 (RIPK1)inhibitor. RI-962 inhibitsRIPK1with anIC50value of 35.0 nM. RI-962 can be used for the research of nervous system diseases and inflammatory diseases[1].
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| IC50& Target |
IC50: 35.0 nM (RIPK1); EC50: 10.0 nM (HT29 cells), 4.2 nM (L929 cells), 11.4 nM (J774A.1 cells), 17.8 nM (U937 cells)[1].
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体外研究
(In Vitro) |
RI-962 has potent inhibitory activity for RIPK1 with an IC50value of 35.0 nM[1].
RI-962 has protective effect for necroptotic death with EC50values of 10.0 nM, 4.2 nM, 11.4 nM, and 17.8 nM for HT29, L929, J774A.1, and U937 cells, respectively[1].
RI-962 (0-100 μM; 24 h) protectes cells from TSZ-induced necroptosis by inhibiting the kinase activity of RIPK1[1].
Cell Viability Assay[1]
| Cell Line: |
HT29, L929, J774A.1, and U937 cells |
| Concentration: |
0-100 μM |
| Incubation Time: |
24 h |
| Result: |
Exerted a dose-dependent protective effect against necroptotic death. |
Western Blot Analysis[1]
| Cell Line: |
HT29 cells |
| Concentration: |
0-400 nM |
| Incubation Time: |
|
| Result: |
Markedly inhibited the phosphorylation of RIPK1 and its downstream signaling proteins RIPK3 and MLKL in a dose-dependent manner. |
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体内研究
(In Vivo) |
RI-962 (i.p.; 40 mg/kg; once a day for 10 day) ameliorates TNFα-induced SIRS and reduces inflammation in acute DSS-induced colitis[1].
Pharmacokinetic Parameters of RI-962 in rats (i.v., i.p., p.o.; 5, 20 mg/kg)[1].
| RI-962 |
i.v. |
p.o. |
i.p. |
| Dose (mg/kg) |
5 |
20 |
20 |
| T1/2(h) |
2.1 ± 0.2 |
1.3 ± 0.2 |
8.5 ± 1.6 |
| Tmax(h) |
0.1 ± 0.0 |
0.8 ± 1.0 |
0.5 ± 0.0 |
| Cmax(ng/mL) |
12170.4 ± 1198.5 |
674.2 ± 424.7 |
3603.3 ± 693.3 |
| AUC0–t(ng*h/mL) |
4526.1 ± 546.0 |
1594.9 ± 891.8 |
6459.7 ± 1131.6 |
| AUC0–∞(ng*h/mL) |
4538.1 ± 546.3 |
1604.5 ± 896.1 |
6609.3 ± 1121.4 |
| Vss(L/kg) |
0.4 ± 0.1 |
- |
- |
| MRT0–∞(h) |
0.4 ± 0.0 |
1.8 ± 0.2 |
2.8 ± 0.1 |
| CL (mL/min/kg) |
18.5 ± 2.1 |
- |
- |
| F (%) |
- |
8.8 ± 5.0 |
35.7 ± 6.3 |
| Animal Model: |
C57BL/6 female mice[1] |
| Dosage: |
40 mg/kg |
| Administration: |
Intraperitoneal for 15 min; once a day for 10 day |
| Result: |
Ameliorated TNFα-induced SIRS by inhibiting RIPK1 activity.
Suppressed the RIPK1 signaling in the mouse model of DSS-induced colitis. |
| Animal Model: |
Sprague-Dawley (SD) rats[1] |
| Dosage: |
5, 20 mg/kg |
| Administration: |
intravenous (i.v.) (5 mg/kg), intraperitoneal (i.p.) (20 mg/kg) and oral (p.o.) (20 mg/kg) |
| Result: |
Had good metabolic stability in rats. |
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| 分子量 |
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| Formula |
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| CAS 号 |
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| 运输条件 |
Room temperature in continental US; may vary elsewhere.
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| 储存方式 |
Please store the product under the recommended conditions in the Certificate of Analysis.
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