NRT-870-59 is a potent, reversible PTP4A3 inhibitor (IC50=86 nM) with inhibitory specificity for PTP4A3 versus both PTP4A3 A111S mutant and CDC25B.
NRT-870-59 does not inhibit CDC25B and PTP4A3 A111S mutant at 1 uM, and 5- to 6-fold less potent aginst DUSP3.
NRT-870-59 inhibits PTP4A1, PTP4A2, PTP4A3 mutants C49S, K144I and A106V with IC50 of 133.2, 264.4, 86.0, 332.2, 180.2 and 57.7 nM, respectively.
NRT-870-59 inhibits cancer cell colony formation, which is required PTP4A3 expression.
The PTP4A (phosphatase of regenerating liver/PRL) phosphatases are a unique subfamily of protein tyrosine phosphatases (PTPs) comprising three highly homologous members (PTP4A1, PTP4A2, and PTP4A3) with 80% amino acid sequence identity.
PTP4A3, and to a lesser extent PTP4A1 and PTP4A2, are overexpressed in many types of cancer, promote tumor invasion and dissemination, and contribute to poor patient prognosis.