Discovery of a synthetic Aminopeptidase N inhibitor LB-4b as a potential anticancer agent

Li Su; Yuping Jia; Xuejian Wang; Lei Zhang; Hao Fang; Wenfang Xu

doi:10.1016/j.bmcl.2013.03.021

Discovery of a synthetic Aminopeptidase N inhibitor LB-4b as a potential anticancer agent

Bioorg Med Chem Lett. 2013 May 1;23(9):2512-7. doi: 10.1016/j.bmcl.2013.03.021. Epub 2013 Mar 13.

Authors

Li Su¹, Yuping Jia, Xuejian Wang, Lei Zhang, Hao Fang, Wenfang Xu

Affiliation

¹ Department of Medicinal Chemistry, School of Pharmacy, Shandong University, Jinan, Shandong 250012, PR China.

PMID: 23528299
DOI: 10.1016/j.bmcl.2013.03.021

Abstract

APN inhibitors have been considered as potential anticancer agents for years. LB-4b is the first synthetic APN inhibitor to be evaluated for both of its anti-invasion and anti-angiogenesis effects. As a potent synthetic APN inhibitor (IC50=850 nM, versus bestatin of 8.1 μM), LB-4b was determined to have more significant block effects to cancer cell invasion and angiogenesis than bestatin. Besides, it is able to be easily synthesized with a high total yield, while the reported synthetic methods of bestatin are much more complex.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Aorta / cytology
Aorta / drug effects
Benzyl Compounds / chemical synthesis*
Benzyl Compounds / chemistry
Benzyl Compounds / pharmacology
CD13 Antigens / antagonists & inhibitors*
CD13 Antigens / metabolism
Cell Line, Tumor
Cell Movement / drug effects
Cell Survival / drug effects
Drug Evaluation, Preclinical
Human Umbilical Vein Endothelial Cells
Humans
Neovascularization, Physiologic
Protease Inhibitors / chemical synthesis
Protease Inhibitors / chemistry*
Protease Inhibitors / pharmacology*
Rats

Substances

Antineoplastic Agents
Benzyl Compounds
LB-4b compound
Protease Inhibitors
CD13 Antigens