Exploring Allosteric Inhibitors of Protein Tyrosine Phosphatases Through High-Throughput Screening

Takeru Hayashi; Masanori Hatakeyama

doi:10.1007/978-1-0716-3331-1_18

Exploring Allosteric Inhibitors of Protein Tyrosine Phosphatases Through High-Throughput Screening

Methods Mol Biol. 2023:2691:235-245. doi: 10.1007/978-1-0716-3331-1_18.

Authors

Takeru Hayashi¹, Masanori Hatakeyama^{2

3}

Affiliations

¹ Laboratory of Microbial Carcinogenesis, Institute of Microbial Chemistry (BIKAKEN), Microbial Chemistry Research Foundation, Tokyo, Japan.
² Laboratory of Microbial Carcinogenesis, Institute of Microbial Chemistry (BIKAKEN), Microbial Chemistry Research Foundation, Tokyo, Japan. mhata@m.u-tokyo.ac.jp.
³ Center of Infection-Associated Cancer, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan. mhata@m.u-tokyo.ac.jp.

PMID: 37355550
DOI: 10.1007/978-1-0716-3331-1_18

Abstract

High-throughput screening (HTS) using a natural or synthetic chemical or natural product library is a powerful technique for discovering novel small-molecular-weight compounds in order to develop drugs that specifically inhibit or activate molecular targets, malfunctioning of which underlies the development of diseases, especially malignant neoplasms. In contrast to a large number of successful cases in obtaining inhibitors against protein tyrosine kinases (PTKs) using HTS, however, the development of selective inhibitors for protein tyrosine phosphatases (PTPs) has lagged since PTP family members share highly conserved catalytic domain structures. Here, in this chapter we describe a novel method for exploring seed compounds of allosteric PTP inhibitors from a chemical/natural product library through HTS.

Keywords: Allosteric inhibitor; High-throughput screening; Protein tyrosine phosphatase; Quality control.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Catalytic Domain
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
High-Throughput Screening Assays* / methods
Protein Tyrosine Phosphatases* / metabolism
Small Molecule Libraries / pharmacology

Substances

Protein Tyrosine Phosphatases
Small Molecule Libraries
Enzyme Inhibitors