SML2376

GSK′963

≥98% (HPLC)

• Synonym(s): 1-[(5S)-4,5-Dihydro-5-phenyl-1H-pyrazol-1-yl]-2,2-dimethyl-1-propanone; 2,2-Dimethyl-1-(5(S)-phenyl-4,5-dihydro-pyrazol-1-yl)-propan-1-one, GSK 963, GSK′ 963A, GSK′963A, GSK-963, GSK-963A, GSK963, GSK963A
• Empirical Formula (Hill Notation): C₁₄H₁₈N₂O
• CAS Number: 2049868-46-2
• Molecular Weight: 230.31
• UNSPSC Code: 12352200
• NACRES: NA.77

Properties

• Assay: ≥98% (HPLC)
• form: powder
• color: white to beige
• solubility: DMSO: 2 mg/mL, clear
• storage temp.: 2-8°C
• SMILES string: O=C(C(C)(C)C)N1[C@H](C2=CC=CC=C2)CC=N1

Description

Biochem/physiol Actions

Brain-penetrant, highly potent and selective RIPK1 (RIP1) inhibitor with necroptosis blocking efficacy in vitro and in vivo.

GSK′963 (GSK′963A) is a brain-penetrant, highly potent and selective ATP site-targeting receptor-interacting protein 1 kinase (RIP1; RIPK1) inhibitor (IC50 = 0.8-8 nM with 50 μM ATP; IC50 >10 μM against RIPK2/3/5 and 335 other kinases) that protects against TNFα/zVAD-induced necroptosis (EC50 = 1/4 nM in mouse L929/human U937 cultures) and blocks Y. pestis-induced death of murine fetal liver macrophages (1 μM). GSK′963 prevents lethal hypothermia by acute sterile shock (2 mg/kg i.p. 15 min prior to TNFα/zVAD i.v.) and protects against acute neuronal death upon autologous blood intracerebral hemorrhage induction in mice in vivo (25 mg/kg/3 hr i.p.).

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable