RGNCY-0103 (PK68 RIPK1 inhibitor)

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PK68 is an inhibitor of RIPK1-dependent necroptosis with an EC50 of 14-22 nM in human and mouse cells.  Upon necroptosis stimuli, PK68 significantly blocks the cellular activation of RIPK1 (with selectivity), RIPK3 and MLKL and has favorable pharmacokinetic properties.  Significantly, PK68 demonstrates strong protection against TNF-a-induced systemic inflammatory response syndrome in vivo.  In addition,PK68 pre-treatment markedly represses metastasis of both melanoma and lung carcinoma cells in mice.  PK68 is a potent and selective inhibitor of RIPK1 and demonstrates potential for the treatment of inflammatory disorders and cancer metastasis.

Systematic Name:  cyclohexyl (5-(2-acetamidobenzo[d]thiazol-6-yl)-2-methylpyridin-3-yl)carbamate

SMILES: CC1=NC=C(C2=CC=C(N=C(NC(C)=O)S3)C3=C2)C=C1NC(OC4CCCCC4)=O

Formula:  C22H24N4O3S

Mol Wt: 424.52

PMID:  31235688