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

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

  • Bioorg Med Chem Lett. 2012 Sep 1;22(17):5748-51. doi: 10.1016/j.bmcl.2012.05.102.
Kevin R Shreder 1,  Emme C K Lin,  Jiangyue Wu,  Julia Cajica,  Christopher M Amantea,  Yi Hu,  Eric Okerberg,  Heidi E Brown,  Lan M Pham,  De Michael Chung,  Allister S Fraser,  Ethel McGee,  Jonathan S Rosenblum,  John W Kozarich
Affiliations

Affiliation

  • 1 ActivX Biosciences, Inc., 11025 N. Torrey Pines Road, La Jolla, CA 92037, USA. kevins@activx.com
PMID: 22877630 DOI: 10.1016/j.bmcl.2012.05.102
Abstract

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.

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