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

RI-962 Chemical Structure

CAS No. : 2763831-53-2

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Based on 1 publication(s) in Google Scholar

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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].
Cellular Effect
Cell Line Type Value Description References
HT-29 EC50
10 nM
Compound: RI-962
Protection against TSZ-induced necroptosis in human HT-29 cells preincubated with compound followed by TNA-alpha,Smac mimetic and Z-VAD-FMK addition and measured after 24 hrs by CCK-8 assay
Protection against TSZ-induced necroptosis in human HT-29 cells preincubated with compound followed by TNA-alpha,Smac mimetic and Z-VAD-FMK addition and measured after 24 hrs by CCK-8 assay
[PMID: 38159286]
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 (HY-116282C)-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
Solvent & Solubility
In Vitro: 

DMSO : 100 mg/mL (208.09 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.0809 mL 10.4045 mL 20.8091 mL
5 mM 0.4162 mL 2.0809 mL 4.1618 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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This equation is commonly abbreviated as: C1V1 = C2V2

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In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Calculation results:
Working solution concentration: mg/mL
Purity & Documentation
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.0809 mL 10.4045 mL 20.8091 mL 52.0226 mL
5 mM 0.4162 mL 2.0809 mL 4.1618 mL 10.4045 mL
10 mM 0.2081 mL 1.0405 mL 2.0809 mL 5.2023 mL
15 mM 0.1387 mL 0.6936 mL 1.3873 mL 3.4682 mL
20 mM 0.1040 mL 0.5202 mL 1.0405 mL 2.6011 mL
25 mM 0.0832 mL 0.4162 mL 0.8324 mL 2.0809 mL
30 mM 0.0694 mL 0.3468 mL 0.6936 mL 1.7341 mL
40 mM 0.0520 mL 0.2601 mL 0.5202 mL 1.3006 mL
50 mM 0.0416 mL 0.2081 mL 0.4162 mL 1.0405 mL
60 mM 0.0347 mL 0.1734 mL 0.3468 mL 0.8670 mL
80 mM 0.0260 mL 0.1301 mL 0.2601 mL 0.6503 mL
100 mM 0.0208 mL 0.1040 mL 0.2081 mL 0.5202 mL
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RI-962 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

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

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