1ONZ

Oxalyl-aryl-Amino Benzoic acid Inhibitors of PTP1B, compound 8b

Summary for 1ONZ

• Entry DOI: 10.2210/pdb1onz/pdb
• Related: 1NL9 1NNY 1NZ7 1No6 1ONY
• Descriptor: Protein-tyrosine phosphatase, non-receptor type 1, 2-[(7-HYDROXY-NAPHTHALEN-1-YL)-OXALYL-AMINO]-BENZOIC ACID (3 entities in total)
• Functional Keywords: protein tyrosine phosphatase, oxalyl-aryl-benzoic acid compound with napthyl moiety anchor inhibitor, 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: 37716.95

Authors

Liu, G.,Szczepankiewicz, B.G.,Pei, Z.,Janowich, D.A.,Xin, Z.,Hadjuk, P.J.,Abad-Zapatero, C.,Liang, H.,Hutchins, C.W.,Fesik, S.W.,Ballaron, S.J.,Stashko, M.A.,Lubben, T.,Mika, A.K.,Zinker, B.A.,Trevillyan, J.M.,Jirousek, M.R. (deposition date: 2003-03-02, release date: 2003-05-20, Last modification date: 2023-08-16)

Primary citation

Liu, G.,Szczepankiewicz, B.G.,Pei, Z.,Janowich, D.A.,Xin, Z.,Hadjuk, P.J.,Abad-Zapatero, C.,Liang, H.,Hutchins, C.W.,Fesik, S.W.,Ballaron, S.J.,Stashko, M.A.,Lubben, T.,Mika, A.K.,Zinker, B.A.,Trevillyan, J.M.,Jirousek, M.R.
Discovery and Structure-Activity Relationship of Oxalylarylaminobenzoic Acids as Inhibitors of Protein Tyrosine Phosphatase 1B
J.Med.Chem., 46:2093-2103, 2003

PubMed Abstract: Protein Tyrosine phosphatase 1B (PTP1B) has been implicated as a key negative regulator of both insulin and leptin signaling pathways. Using an NMR-based screening approach with 15N- and 13C-labeled PTP1B, we have identified 2,3-dimethylphenyloxalylaminobenzoic acid (1) as a general, reversible, and competitive PTPase inhibitor. Structure-based approach guided by X-ray crystallography facilitated the development of 1 into a novel series of potent and selective PTP1B inhibitors occupying both the catalytic site and a portion of the noncatalytic, second phosphotyrosine binding site. Interestingly, oral biovailability has been observed in rats for some compounds. Furthermore, we demonstrated in vivo plasma glucose lowering effects with compound 12d in ob/ob mice.

PubMed: 12747781
DOI: 10.1021/jm0205696
PDB entries with the same primary citation

Experimental method

X-RAY DIFFRACTION (2.4 Å)