Synthesis and structure-activity relationship of (1-halo-2-naphthyl) carbamate-based inhibitors of KIAA1363 (NCEH1/AADACL1).

Autor: Shreder KR; ActivX Biosciences, Inc., 11025 N. Torrey Pines Road, La Jolla, CA 92037, USA. kevins@activx.com, Lin EC, Wu J, Cajica J, Amantea CM, Hu Y, Okerberg E, Brown HE, Pham LM, Chung de M, Fraser AS, McGee E, Rosenblum JS, Kozarich JW
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2012 Sep 01; Vol. 22 (17), pp. 5748-51. Date of Electronic Publication: 2012 Jun 06.
DOI: 10.1016/j.bmcl.2012.05.102
Abstrakt: KIAA1363 is a serine hydrolase whose activity has been shown to be positively associated with tumor cell invasiveness. Thus, inhibitors of KIAA1363 represent a novel targeted therapy approach towards cancer. AX11890 ((1-bromo-2-naphthyl) N,N-dimethylcarbamate) was identified as a KIAA1363 inhibitor with an IC(50) value of 1.2 μM and was shown using ESI-MS to carbamylate the catalytic residue Ser(191). SAR studies explored both substitution of the 1-bromo group and derivatization of the 6-position. Activity-based protein profiling demonstrated AX13057 inhibited tumor-localized KIAA1363 in SK-OV-3 xenograft-bearing mice.
(Copyright © 2012. Published by Elsevier Ltd.)
Databáze: MEDLINE
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