JNK-IN-8

• CAT Number: I001570
• CAS Number: 1410880-22-6
• Molecular Formula: C29H29N7O2
• Molecular Weight: 507.59
• Purity: ≥95%
• Synonyms: 3-[[(E)-4-(dimethylamino)but-2-enoyl]amino]-N-[3-methyl-4-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide
• InChI: InChI=1S/C29H29N7O2/c1-20-17-24(11-12-25(20)34-29-31-15-13-26(35-29)22-8-5-14-30-19-22)33-28(38)21-7-4-9-23(18-21)32-27(37)10-6-16-36(2)3/h4-15,17-19H,16H2,1-3H3,(H,32,37)(H,33,38)(H,31,34,35)/b10-6+
• InChIKey: GJFCSAPFHAXMSF-UXBLZVDNSA-N
• SMILES: CC1=C(C=CC(=C1)NC(=O)C2=CC(=CC=C2)NC(=O)C=CCN(C)C)NC3=NC=CC(=N3)C4=CN=CC=C4

JNK-IN-8 (JNK Inhibitor XVI) is a potent JNK inhibitor with IC50s of 4.7 nM, 18.7 nM, and 1 nM for JNK1, JNK2, and JNK3, respectively[1].
JNK-IN-8 inhibits phosphorylation of c-Jun, a direct substrate of JNK kinase. JNK-IN-8 inhibits c-Jun phosphorylation in HeLa and A375 cells with EC50 of 486 nM and 338 nM, respectively. JNK-IN-8 also exhibits exceptional selectivity based upon KinomeScan and enzymatic profiling. Cumulatively these combined profiling technologies demonstrate that both JNK-IN-8 and JNK-IN-12 are remarkably selective covalent JNK inhibitors and are appropriate for interrogating JNK-dependent biological phenomena[1].JNK-IN-8, a selective pan-JNK inhibitor, is discovered to inhibit JNK kinase by broad-base kinase selectivity profiling of a library of acrylamide kinase inhibitors based on the structure of imatinib using the KinomeSca approach. JNK-IN-8 possess distinct regio-chemistry of the 1,4-dianiline and 1,3-aminobenzoic acid substructures relative to imatinib and uses an N,N-dimethyl butenoic actemide warhead to covalently target Cys154. JNK-IN-8 adopts an L-shaped type I binding conformation to access Cys 154 located towards the lip of the ATP-binding site[2].

Reference

[1]. Zhang T, et al. Discovery of potent and selective covalent inhibitors of JNK. Chem Biol. 2012 Jan 27;19(1):140-54.
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[2]. Liu Q, et al. Developing irreversible inhibitors of the protein kinase cysteinome. Chem Biol. 2013 Feb 21;20(2):146-59.
 [Content Brief]