- 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).
Bioorganic & medicinal chemistry letters (2012-08-11)
Kevin R Shreder, 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
PMID22877630
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.
MATERIALS
Product Number
Brand
Product Description
Sigma-Aldrich
Cholesterol Esterase from Pseudomonas sp., lyophilized powder, ≥200,000 units/g protein
Sigma-Aldrich
Cholesterol Esterase from Pseudomonas fluorescens, lyophilized powder, ≥10,000 units/g protein
Sigma-Aldrich
Cholesterol Esterase from bovine pancreas, lyophilized powder, ≥200 units/g protein