JH-RE-06

• CAT Number: I018710
• CAS Number: 1361227-90-8
• Molecular Formula: C20H16Cl3N3O4
• Molecular Weight: 468.72
• Purity: ≥95%
• Synonyms: 8-chloro-2-(2,4-dichloroanilino)-3-(3-methylbutanoyl)-5-nitro-1H-quinolin-4-one
• InChI: InChI=1S/C20H16Cl3N3O4/c1-9(2)7-15(27)17-19(28)16-14(26(29)30)6-4-11(22)18(16)25-20(17)24-13-5-3-10(21)8-12(13)23/h3-6,8-9H,7H2,1-2H3,(H2,24,25,28)
• InChIKey: LRTXIQCBQIKIOH-UHFFFAOYSA-N
• SMILES: CC(C)CC(=O)C1=C(NC2=C(C=CC(=C2C1=O)[N+](=O)[O-])Cl)NC3=C(C=C(C=C3)Cl)Cl

JH-RE-06, a potent REV1-REV7 interface inhibitor (IC50=0.78 μM; Kd=0.42 μM), targets REV1 that interacts with the REV7 subunit of POLζ. JH-RE-06 disrupts mutagenic translesion synthesis (TLS) by preventing recruitment of mutagenic POLζ. JH-RE-06 improves chemotherapy[1][2].
JH-RE-06 unexpectedly induces dimerization of the REV1 CTD at its REV7-binding surface and blocks the REV1-REV7 interaction[1].
JH-RE-06 inhibits mutagenic TLS and enhances cisplatin-induced toxicity in cultured human and mouse cell lines[1].
Co-administration of JH-RE-06 with cisplatin suppresses the growth of xenograft human melanomas in mice[1].

Reference

[1]. Wojtaszek JL, et al. A Small Molecule Targeting Mutagenic Translesion Synthesis Improves Chemotherapy. Cell. 2019 Jun 27;178(1):152-159.e11.
 [Content Brief]

[2]. REV1-POLς Inhibition Enhances Cisplatin-Induced Cytotoxicity. Cancer Discov. 2019 Aug;9(8):OF17.