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Protein tyrosine phosphatase (PTP) inhibitors block enzymes that remove phosphate groups from tyrosine residues. PTPs counterbalance tyrosine kinases, and the classical PTPs share a catalytic cysteine within a conserved active-site motif. Mice lacking PTP1B show increased insulin sensitivity, which made this enzyme a model target in metabolic signaling research. SHP099 and SHP394 are allosteric inhibitors of Src homology 2 domain-containing phosphatase 2 (SHP2), which relays signals from receptor tyrosine kinases. NSC 87877 acts at the catalytic sites of SHP1 and SHP2, and TCS 401 free base inhibits PTP1B. Alexidine dihydrochloride inhibits PTP localized to the mitochondrion 1 (PTPMT1), a phosphatase located in the inner mitochondrial membrane.
SC-43, a Sorafenib derivative, is a potent and orally active SHP-1 (PTPN6) agonist. SC-43 inhibits the phosphorylation of STAT3 and induces cell apoptosis. SC-43 has anti-fibrotic and anticancer effects.
