Phosphatase Inhibitor

Icerguastat (Sephin1), a derivative of Guanabenz lacking the α2-adrenergic activity, is a selective inhibitor of the phosphatase regulatory subunit PPP1R15A (R15A). Icerguastat inhibits eIF2α dephosphorylation, thereby prolonging the protective response. Anti-prion effect.

RMC-4550 is a potent, selective and allosteric inhibitor of SHP2, with an IC₅₀ of 0.583 nM.

SF1670 is a potent and specific phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibitor.

Razuprotafib (AKB-9778) is a potent and selective inhibitor of the catalytic activity of VE-PTP (vascular endothelial protein tyrosine phosphatase) with an IC₅₀of 17 pM. Razuprotafib promotes TIE2 activation, enhances ANG1-induced TIE2 activation, and stimulates phosphorylation of signaling molecules in the TIE2 pathway, including AKT, eNOS, and ERK. Razuprotafib inhibits the structurally related phosphatase PTP1B with an IC₅₀ of 780 nM. Razuprotafib shows excellent selectivity for VE-PTP versus a variety of phosphatases, with the exception of HPTPη (IC₅₀=36 pM) and HPTPγ (100 pM).

Morin is an orally active plant-derived flavonoid. Morin inhibits ROS generation. Morin induces Apoptosis. Morin inhibits PTP1B (IC₅₀ of 15 μM) and activates the insulin receptor. Morin has a detoxifying effect. Morin can be used in diabetes, leukemia, colon cancer, cervical cancer, Parkinson's disease and hypertension research.

GSK 2830371 is a highly selective Wip1 phosphatase inhibitor with IC₅₀ of 6 nM.

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.

Pentamidine (MP-601205) is an antimicrobial agent and interferes with DNA biosynthetics. Pentamidine inhibits parasite Leishmania infantum with an IC₅₀ of 2.5 μM. Pentamidine is a potent and selective protein tyrosine phosphatases (PTPases) and phosphatase of regenerating liver (PRL) inhibitor. Pentamidine has the potential for Gambian trypanosomiasis, antimony-resistant leishmaniasis, and Pneumocystis carinii pneumonia treatment. Antitumor and antibacterial activities.

NSC-87877 is a potent inhibitor of Shp2 and Shp1 protein tyrosine phosphatases (SH-PTP2 and SH-PTP1), with IC₅₀ values of 0.318 μM, 0.355 μM shp2 and shp1, respectively. NSC-87877 also inhibits dual-specificity phosphatase 26 (DUSP26).

3α-Aminocholestane is a selective SH2 domain-containing inositol-5′-phosphatase 1 (SHIP1) inhibitor with an IC₅₀ of ~2.5 μM.

Pentamidine isethionate (MP-601205 isethionate) is an antimicrobial agent and interferes with DNA biosynthetics. Pentamidine isethionate inhibits parasite Leishmania infantum with an IC₅₀ of 2.5 μM. Pentamidine isethionate is a potent and selective protein tyrosine phosphatases (PTPases) and phosphatase of regenerating liver (PRL) inhibitor. Pentamidine isethionate has the potential for Gambian trypanosomiasis, antimony-resistant leishmaniasis, and Pneumocystis carinii pneumonia treatment. Antitumor and antibacterial activities.

NSC 95397 is a potent, selective Cdc25 dual specificity phosphatase inhibitor (K_i=32 nM (Cdc25A), 96 nM (Cdc25B), 40 nM (Cdc25C); IC₅₀=22.3 nM (human Cdc25A), 56.9 nM (human Cdc25C), 125 nM (Cdc25B)). NSC 95397 inhibits mitogen-activated protein kinase phosphatase-1 (MKP-1) and suppresses proliferation and induces apoptosis in colon cancer cells through MKP-1 and ERK1/2 pathway.

Sal003 is a potent, specific and cell-permeable inhibitor of the eukaryotic translation initiation factor 2α (eIF2α) phosphatase. Sal003 is a derivative of salubrinal.

AZ-PFKFB3-67 is a potent and selective PFKFB3 kinase inhibitor with IC₅₀s of 11, 159 and 1130 nM for PFKFB3, PFKFB2 and PFKFB1, respectively. AZ-PFKFB3-67 reduces MCL-1. AZ-PFKFB3-67 has neuroprotective activity.

DCP-LA (FR236924), a linoleic acid derivative, selectively and directly activates PKCε. DCP-LA activates Ca(²⁺)/calmodulin-dependent protein kinase II (CaMKII) and inhibits protein phosphatase-1 (PP-1) to stimulate AMPA receptor exocytosis. DCP-LA inhibits activation of caspase-3/-9 and protects neurons at least in part from oxidative stress-induced apoptosis.

Vociprotafib (RMC-4630) is an orally active, selective and potent phosphatase SHP2 inhibitor, which blocks activation of the RAS-RAF-MEK-ERK signaling pathway with antitumor activity. Vociprotafib accelerates the time to, and increases the magnitude of, tumor regressions in Osimertinib (HY-15772)-sensitive EGFR-mutant tumors of mice.

MSI-1436 lactate is a selective, non-competitive inhibitor of the enzyme protein-tyrosine phosphatase 1B (PTP1B), with an IC₅₀ of 1 μM, 200-fold preference over TCPTP (IC₅₀ of 224 μM).

FR054 is an inhibitor of the HBP enzyme PGM3, with a remarkable anti-breast cancer effect.

NAZ2329, the first cell-permeable inhibitor of R5 subfamily of receptor-type protein tyrosine phosphatases (RPTPs), allosterically and preferentially inhibits PTPRZ (IC₅₀=7.5 µM for hPTPRZ1) and PTPRG (IC₅₀=4.8 µM for hPTPRG) over other PTPs. NAZ2329 binds to the active D1 domain and more potently inhibits PTPRZ-D1 fragment (IC₅₀ of 1.1 µM) than the whole intracellular (D1 + D2) fragment (IC₅₀ of 7.5 µM). NAZ2329 can effectively inhibit tumor growth of the glioblastoma cells and suppress stem cell-like properties.

BCI-215 is a potent and tumor cell-selective dual specificity MAPK phosphatase (DUSP-MKP) inhibitor. BCI-215 has cytotoxicity for tumor cells but not normal cells.