2. Apoptosis
  3. RIP kinase Necroptosis
  4. RI-962

RI-962 is a potent and selective receptor-interacting protein kinase 1 (RIPK1) inhibitor. RI-962 inhibits RIPK1 with an IC50 value of 35.0 nM. RI-962 can be used for the research of nervous system diseases and inflammatory diseases.

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RI-962 Chemical Structure

RI-962 Chemical Structure

CAS No. : 2763831-53-2

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Description

RI-962 is a potent and selective receptor-interacting protein kinase 1 (RIPK1) inhibitor. RI-962 inhibits RIPK1 with an IC50 value of 35.0 nM. RI-962 can be used for the research of nervous system diseases and inflammatory diseases[1].

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].
In Vitro

RI-962 has potent inhibitory activity for RIPK1 with an IC50 value of 35.0 nM[1].
RI-962 has protective effect for necroptotic death with EC50 values 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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

RI-962 Related Antibodies

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.
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

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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.
Molecular Weight

480.56

Formula

C28H28N6O2
CAS No.
Appearance

Solid

Color

Off-white to light yellow

SMILES

O=C(C1=CN(C)C2=C1C=C(C3=CC4=NC(NC(C(C)C)=O)=NN4C=C3)C=C2)NC(C)C5=CC=CC=C5
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Purity & Documentation
References
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Keywords:

RI-9622763831-53-2RI962RI 962RIP kinaseNecroptosisReceptor-interacting protein kinasesRIPKkinasesreceptor-interacting protein kinase 1 (RIPK1)nervous system diseasesinflammatory diseasesInhibitorinhibitorinhibit

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