| Field | Specification |
|---|---|
| CAS no. | |
| Applications | |
| Molecular weight | |
| Molecular formula | C28H28N6O2 |
| Purity | |
| SMILES | |
| Form | Solid |
| Storage | |
| Shipping | |
| Catalog no. (Mfr.) | |
| Main SKU |
Compound Overview
RI-962 is a potent, selective inhibitor of receptor-interacting protein kinase 1 (RIPK1), with an IC50 value of 35.0 nM. It can be used for research into nervous system diseases and inflammatory diseases[1]. It is supplied as an off-white to light yellow solid (C28H28N6O2, MW 480.56) at 99.50% purity.
Physical & Chemical Properties
| CAS Number | 2763831-53-2 |
|---|---|
| Molecular Formula | C28H28N6O2 |
| Molecular Weight | 480.56 g/mol |
| Purity | 99.50% |
| 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 |
| Signaling Pathway | Apoptosis |
| Solubility | In Vitro: DMSO: 100 mg/mL (208.09 mM; Requires sonication; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO) |
| Storage | Powder: -20°C, 3 years; 4°C, 2 years. In solvent: -80°C, 6 months; -20°C, 1 month. |
| Shipping | Room temperature in continental US; may vary elsewhere. |
Biological Activity
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].
Literature Cited
Sources cited in this description and in the In Vitro & In Vivo Data tab. Peer-reviewed publications that used this product are listed under References.
Safety
For Research Use Only. Not for use in diagnostic or therapeutic procedures, and not for human or veterinary use. Handle in accordance with the Safety Data Sheet and your institution's chemical hygiene plan.
In Vitro
| Solvent | Solubility | Notes |
|---|---|---|
| DMSO | 100 mg/mL (208.09 mM) | requires sonication; use freshly opened DMSO (absorbed moisture lowers solubility) |
Aliquot the stock solution and store it at -80°C (up to 6 months) or -20°C (up to 1 month); avoid repeated freeze-thaw cycles.
Data provided by the manufacturer.
In Vitro
RI-962 potently inhibits RIPK1, with an IC50 value of 35.0 nM[1]. RI-962 protects against necroptotic death in HT29, L929, J774A.1, and U937 cells, with EC50 values of 10.0, 4.2, 11.4, and 17.8 nM, respectively[1]. By inhibiting the kinase activity of RIPK1, RI-962 (0-100 μM; 24 h) protects cells from necroptosis induced by TSZ[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.
In Vivo
RI-962 (i.p.; 40 mg/kg; once a day for 10 days) ameliorates TNFα-induced SIRS and lowers inflammation in acute colitis induced by DSS[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. |
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
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