| Identification | Back Directory | [Name]
RIPA-56 | [CAS]
1956370-21-0 | [Synonyms]
RIPA-56
RIPA56; RIPA 56
RIPA-56 >=98% (HPLC)
Butanamide, N-hydroxy-2,2-dimethyl-N-(phenylmethyl)- | [Molecular Formula]
C13H19NO2 | [MOL File]
1956370-21-0.mol | [Molecular Weight]
221.3 |
| Chemical Properties | Back Directory | [Boiling point ]
346.0±35.0 °C(Predicted) | [density ]
1.070±0.06 g/cm3(Predicted) | [storage temp. ]
-20°C | [solubility ]
Soluble in DMSO (up to 50 mg/ml) or in Ethanol (up to 50 mg/ml) | [form ]
solid | [pka]
9.42±0.50(Predicted) | [color ]
White | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months. |
| Hazard Information | Back Directory | [Description]
RIPA-56 (1956370-21-0) is a potent (IC50?= 13 nM, EC50?= 28nM for HT-29 cells) and selective inhibitor of Receptor-Interacting Protein 1 (RIP1) kinase with significant metabolic stability (t1/2?= 128min human liver microsomal stability assay).? RIPA-56 showed excellent kinase selectivity and did not inhibit IDO at 200 μM.?It was able to block the progression of multiple sclerosis in an immune-induced demyelination model.2 | [Uses]
RIPA-56 is a highly potent, selective, and metabolically stable inhibitor of receptor-interacting
protein 1 (RIP1) with an IC50 of 13 nM. RIPA-56 can be used for the treatment of systemic inflammatory response syndrome[1]. | [Biochem/physiol Actions]
RIPA-56 is a metabolically stable type III kinase inhibitor that targets receptor-interacting protein 1 kinase (RIP1; RIPK1) in a highly potent and selective manner (RIP1 IC50 = 13 nM) by locking RIP1 in its inactive form, exhibiting no inhibitory potency toward RIP3, IDO or a panel of multiple kinases (tested at 10, 200, and 5 μM, respectively). RIPA-56 protects against TNFα-induced necroptosis (necrosis) upon apoptosis/NF-κB pathway blockage (EC50?= 27 nM/murine L929 and 28 nM/human HT-29 cells) in cultures as well as TNFα-induced mortality and multiorgan damage in a murine model of systemic inflammatory response syndrome (SIRS) in vivo (100% survival rate with 3 mg/kg/12 h or single 6 mg/kg i.p.) with good pharmacokinetics and bioavailability (F post 10 mg/kg p.o. or i.p. dosing = 22% and 100%, respectively, of 2 mg/kg i.v.). Long-term daily RIPA-56 supplementation (150 or 300 mg/kg in chow) is reported to prevent aging-associated deterioration of the male reproductive system in mice. | [in vivo]
In the SIRS mice disease model, RIPA-56 efficiently reduces tumor necrosis factor alpha (TNFα)-induced mortality and multi-organ damage. Compared to known RIP1 inhibitors, RIPA-56 is potent in both human and murine cells, is much more stable in vivo, and is efficacious in animal model studies. RIPA-56 has an impressive PK profile in mice with a 3.1 h half-life, 22% oral bioavailability (P.O.), and 100% bioavailability from intraperitoneal injection (I.P.)[1]. | [storage]
Store at -20°C | [References]
1) Ren?et al.?(2017),?Discovery of a Highly Potent, Selective, and Metabolically Stable Inhibitor of Receptor-Interacting Protein 1 (RIP1) for the Treatment of Systemic Inflammatory Response Syndrome; J. Med. Chem.?60?972 |
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