RIPA-56 Property

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 and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

Precautionary statements

P280Wear protective gloves/protective clothing/eye protection/face protection.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P337+P313IF eye irritation persists: Get medical advice/attention.

RIPA-56 Chemical Properties,Usage,Production

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

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.

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