8JBN

Vascular endothelial protein tyrosine phosphatase in complex with Cpd-1

Summary for 8JBN

• Entry DOI: 10.2210/pdb8jbn/pdb
• Descriptor: Receptor-type tyrosine-protein phosphatase beta, 1,2-ETHANEDIOL, 5-(1~{H}-indol-3-yl)-1,2-oxazole-3-carboxylic acid, ... (5 entities in total)
• Functional Keywords: protein tyrosine phosphatase, fbdd, inhibitor, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 68765.65

Authors

Orita, T.,Furuzono, T.,Doi, S.,Adachi, T. (deposition date: 2023-05-09, release date: 2024-02-28)

Primary citation

Asano, W.,Yamanaka, K.,Ohara, Y.,Uhara, T.,Doi, S.,Orita, T.,Iwanaga, T.,Adachi, T.,Fujioka, S.,Akaki, T.,Ikegashira, K.,Hantani, Y.
Fragment-Based Discovery of Novel VE-PTP Inhibitors Using Orthogonal Biophysical Techniques.
Biochemistry, 62:2161-2169, 2023

PubMed Abstract: Tyrosine phosphorylation is an essential post-translational modification that regulates various biological events and is implicated in many diseases including cancer and atherosclerosis. Vascular endothelial protein tyrosine phosphatase (VE-PTP), which plays an important role in vascular homeostasis and angiogenesis, is therefore an attractive drug target for these diseases. However, there are still no drugs targeting PTP including VE-PTP. In this paper, we report the discovery of a novel VE-PTP inhibitor, Cpd-2, by fragment-based screening combining various biophysical techniques. Cpd-2 is the first VE-PTP inhibitor with a weakly acidic structure and high selectivity, unlike known strongly acidic inhibitors. We believe that this compound represents a new possibility for the development of bioavailable VE-PTP inhibitors.

PubMed: 37414577
DOI: 10.1021/acs.biochem.3c00079

Experimental method

X-RAY DIFFRACTION (1.99 Å)