SML2745

GSK′481

≥98% (HPLC)

• Synonym(s): (S)-5-Benzyl-N-(5-methyl-4-oxo-2,3,4,5-tetrahydrobenzo[b]-[1,4]oxazepin-3-yl)isoxazole-3-carboxamide, GSK 2882481, GSK 481, GSK-2882481, GSK-481, GSK2882481, GSK481
• Empirical Formula (Hill Notation): C₂₁H₁₉N₃O₄
• CAS Number: 1622849-58-4
• Molecular Weight: 377.39
• MDL number: MFCD30343843
• UNSPSC Code: 12352200
• NACRES: NA.77

Properties

• Quality Level: 100
• Assay: ≥98% (HPLC)
• form: powder
• color: white to beige
• solubility: DMSO: 2 mg/mL, clear
• storage temp.: −20°C
• SMILES string: N1(c2c(cccc2)OC[C@@H](C1=O)NC(=O)c3n[o]c(c3)Cc4ccccc4)C
• InChI: 1S/C21H19N3O4/c1-24-18-9-5-6-10-19(18)27-13-17(21(24)26)22-20(25)16-12-15(28-23-16)11-14-7-3-2-4-8-14/h2-10,12,17H,11,13H2,1H3,(H,22,25)/t17-/m0/s1
• InChI key: KNOUWGGQMADIBV-KRWDZBQOSA-N

Description

Biochem/physiol Actions

A highly selective ATP site-targeting inhibitor against human/monkey, but not non-primate, RIP1.

GSK′481 is a highly potent receptor interacting protein 1 kinase (RIP1, RIPK1) inhibitor (human/monkey RIP1 IC₅₀ = 1.6/2.5 nM; [ATP] = 50 μM) that targets RIP1 ATP-binding pocket with high affinity (k_on = 0.66/μM/sec, t_1/2 = 11 min) with little potency toward non-primate RIP1 (IC₅₀ = 2.0/3.2/6.3/7.9/>10 μM against rabbit/mouse/rat/dog/minipig RIP1) and no off-target affinity when profiled at 10 μM by a 456-kinase panel. GSK′481 blocks caspase inhibitor/TNF-induced necroptosis in human monocytic U937 cultures (IC₅₀ = 10 nM) and inhibits S166 autophosphorylation of exogenously expressed human, but not mouse, RIP1 in HEK293T transfectants (IC₅₀ = 2.8 nM and >10 μM, respectively).

Safety Information

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