1NZ7

POTENT, SELECTIVE INHIBITORS OF PROTEIN TYROSINE PHOSPHATASE 1B USING A SECOND PHOSPHOTYROSINE BINDING SITE, complexed with compound 19.

Summary for 1NZ7

• Entry DOI: 10.2210/pdb1nz7/pdb
• Related: 1NL9 1NNY 1No6 1ONY 1ONZ
• Descriptor: Protein-tyrosine phosphatase, non-receptor type 1, 2-[(4-{2-ACETYLAMINO-2-[4-(1-CARBOXY-3-METHYLSULFANYL-PROPYLCARBAMOYL)-BUTYLCARBAMOYL]-ETHYL}-2-ETHYL-PHENYL)-OXALYL-AM INO]-BENZOIC ACID (3 entities in total)
• Functional Keywords: protein tyrosine phosphatase fold, oxamic acid inhibitor bound to p-loop, 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: 38038.38

Authors

Xin, Z.,Oost, T.K.,Abad-Zapatero, C.,Hajduk, P.J.,Pei, Z.,Szczepankiewicz, B.G.,Hutchins, C.W.,Ballaron, S.J.,Stashko, M.A.,Lubben, T.,Trevillyan, J.M.,Jirousek, M.R.,Liu, G. (deposition date: 2003-02-16, release date: 2003-05-20, Last modification date: 2023-08-16)

Primary citation

Xin, Z.,Oost, T.K.,Abad-Zapatero, C.,Hajduk, P.J.,Pei, Z.,Szczepankiewicz, B.G.,Hutchins, C.W.,Ballaron, S.J.,Stashko, M.A.,Lubben, T.,Trevillyan, J.M.,Jirousek, M.R.,Liu, G.
Potent, Selective Inhibitors of Protein Tyrosine Phosphatase 1B
BIOORG.MED.CHEM.LETT., 13:1887-1890, 2003

PubMed Abstract: We have previously reported a novel series of oxalyl-aryl-amino benzoic acid-based, catalytic site-directed, competitive, reversible protein tyrosine phosphatase 1B (PTP1B) inhibitors. With readily access to key intermediates, we utilized a solution phase parallel synthesis approach and rapidly identified a highly potent PTP1B inhibitor (19, K(i)=76 nM) with moderate selectivity (5-fold) over T-cell PTPase (TCPTP) through interacting with a second phosphotyrosine binding site (site 2) in the close proximity to the catalytic site.

PubMed: 12749891
DOI: 10.1016/S0960-894X(03)00302-0

Experimental method

X-RAY DIFFRACTION (2.4 Å)