1Q1M

A Highly Efficient Approach to a Selective and Cell Active PTP1B inhibitors

Summary for 1Q1M

• Entry DOI: 10.2210/pdb1q1m/pdb
• Related: 1NL9 1NNY 1NO6 1NZ7 1ONY 1PHO
• Descriptor: Protein-tyrosine phosphatase, non-receptor type 1, 5-{2-FLUORO-5-[3-(3-HYDROXY-2-METHOXYCARBONYL-PHENOXY)-PROPENYL]-PHENYL}-ISOXAZOLE-3-CARBOXYLIC ACID (3 entities in total)
• Functional Keywords: protein tyrosine phosphatase 1b, ptp1b, inhibitors with isoxazole-salicylate pharmacophores, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Endoplasmic reticulum membrane ; Peripheral membrane protein ; Cytoplasmic side : P18031
• Total number of polymer chains: 1
• Total formula weight: 37778.99

Authors

Liu, G.,Xin, Z.,Pei, Z.,Hajduk, P.J.,Abad-Zapatero, C.,Hutchins, C.W.,Zhao, H.,Lubben, T.H.,Ballaron, S.J.,Haasch, D.L.,Kaszubska, W.,Rondinone, C.M.,Trevillyan, J.M.,Jirousek, M.R. (deposition date: 2003-07-22, release date: 2003-09-16, Last modification date: 2023-08-16)

Primary citation

Liu, G.,Xin, Z.,Pei, Z.,Hajduk, P.J.,Abad-Zapatero, C.,Hutchins, C.W.,Zhao, H.,Lubben, T.H.,Ballaron, S.J.,Haasch, D.L.,Kaszubska, W.,Rondinone, C.M.,Trevillyan, J.M.,Jirousek, M.R.
Fragment screening and assembly: a highly efficient approach to a selective and cell active protein tyrosine phosphatase 1B inhibitor.
J.Med.Chem., 46:4232-4235, 2003

PubMed Abstract: Using an NMR-based fragment screening and X-ray crystal structure-based assembly, starting with millimolar ligands for both the catalytic site and the second phosphotyrosine binding site, we have identified a small-molecule inhibitor of protein tyrosine phosphatase 1B with low micromolar inhibition constant, high selectivity (30-fold) over the highly homologous T-cell protein tyrosine phosphatase, and good cellular activity in COS-7 cells.

PubMed: 13678400
DOI: 10.1021/jm034122o

Experimental method

X-RAY DIFFRACTION (2.6 Å)