1ONZ

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

1ONZ の概要

• エントリーDOI: 10.2210/pdb1onz/pdb
• 関連するPDBエントリー: 1NL9 1NNY 1NZ7 1No6 1ONY
• 分子名称: Protein-tyrosine phosphatase, non-receptor type 1, 2-[(7-HYDROXY-NAPHTHALEN-1-YL)-OXALYL-AMINO]-BENZOIC ACID (3 entities in total)
• 機能のキーワード: protein tyrosine phosphatase, oxalyl-aryl-benzoic acid compound with napthyl moiety anchor inhibitor, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endoplasmic reticulum membrane ; Peripheral membrane protein ; Cytoplasmic side : P18031
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37716.95

構造登録者

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. (登録日: 2003-03-02, 公開日: 2003-05-20, 最終更新日: 2023-08-16)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.4 Å)