Download MendeleyDiscovery of potent, reversible MetAP2 inhibitors via fragment based drug discovery and structure based drug design-Part 1.
Cheruvallath, Z., Tang, M., McBride, C., Komandla, M., Miura, J., Ton-Nu, T., Erikson, P., Feng, J., Farrell, P., Lawson, J.D., Vanderpool, D., Wu, Y., Dougan, D.R., Plonowski, A., Holub, C., Larson, C.(2016) Bioorg Med Chem Lett 26: 2774-2778
- PubMed: 27155900
- DOI: https://doi.org/10.1016/j.bmcl.2016.04.073
- Primary Citation of Related Structures:
5JHU, 5JI6 - PubMed Abstract:
Methionine aminopeptidase 2 (MetAP2) is an enzyme that cleaves an N-terminal methionine residue from a number of newly synthesized proteins. Pre-clinical and clinical studies suggest that MetAP2 inhibitors could be used as a novel treatment for obesity. Herein we describe our use of fragment screening methods and structural biology to quickly identify and elaborate an indazole fragment into a series of reversible MetAP2 inhibitors with <10nM potency, excellent selectivity, and favorable in vitro safety profiles.
Organizational Affiliation:
Medicinal Chemistry, Takeda California, United States.
