2. Academic Validation
  3. Fragment-Based Discovery of Novel VE-PTP Inhibitors Using Orthogonal Biophysical Techniques

Fragment-Based Discovery of Novel VE-PTP Inhibitors Using Orthogonal Biophysical Techniques

  • Biochemistry. 2023 Jul 18;62(14):2161-2169. doi: 10.1021/acs.biochem.3c00079.
Wataru Asano 1,  Kenji Yamanaka 1,  Yasunori Ohara 1,  Toru Uhara 1,  Satoki Doi 2,  Takuya Orita 2,  Tomoko Iwanaga 2,  Tsuyoshi Adachi 2,  Shingo Fujioka 2,  Tatsuo Akaki 2,  Kazutaka Ikegashira 2,  Yoshiji Hantani 1
Affiliations

Affiliations

  • 1 Biological/Pharmacological Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
  • 2 Chemical Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
PMID: 37414577 DOI: 10.1021/acs.biochem.3c00079
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.

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