phosphatases

Suramin Sodium Salt (BAY-205) is a sodium salt form of suramin, a polysulphonated naphthylurea with potential antineoplastic activity. Suramin blocks the binding of various growth factors, including insulin-like growth factor I (IGF-I), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and tumor growth factor-beta (TGF-beta), to their receptors, thereby inhibiting endothelial cell proliferation and migration. This agent also inhibits vascular endothelial growth factor (VEGF)- and basic fibroblast growth factor (bFGF)-induced angiogenesis; retroviral reverse transcriptase; uncoupling of G-proteins from receptors; topoisomerases; cellular folate transport; and steroidogenesis.

PD 198306 is a selective inhibitor of MAPK ERK-kinase (MEK) with antihyperalgesic effects. PD 198306 reduces the Streptozocin-induced increase in the level of active ERK1.

Pentamidine dihydrochloride (MP-601205 dihydrochloride) is an aromatic diamidine agent effective against various microorganisms, including protozoa (Trypanosoma brucei, Leishmania spp., and Babesia spp.) and fungi (Pneumocystis jirovecii). It is a potent and selective inhibitor of protein tyrosine phosphatases and phosphatase of regenerating liver. Pentamidine dihydrochloride inhibits the parasite Leishmania infantum with an IC50 of 2.5 μM.

Tyrphostin 8(4-Hydroxybenzylidenemalononitrile) is a potent GTPase inhibitor that inhibits EGFR kinase with an IC50 of 560 μM.Tyrphostin 8 inhibits protein serine threonine calmodulin phosphatases (IC50=21 μM), enhances transferrin receptor-mediated transcytosis in Caco-2 cells, and increases the hypoglycemic effect of oral insulin-transferrin. hypoglycemic effect.

2-Bromo-4'-hydroxyacetophenone(PTP Inhibitor I) is a cell-permeable, protein tyrosine phosphatase (PTP) inhibitor that covalently blocks the catalytic domain of the Src homology region 2 domain-containing phosphatase (SHP-1(ΔSH2)) with a Ki value of 43 μM and PTP1B with a Ki value of 42 μM [1]. SHP-1 and PTP1B both have known roles in regulating insulin signaling as well as myeloid and lymphoid cell differentiation, making inhibitors of these phosphatases of interest in diabetes, cancer, allergy, and inflammation research [2].

2-(2-Aminothiazole-4-yl)-2-methoxyiminoa is an inhibitor of protein tyrosine phosphatases, which can lead to changes in cellular signaling pathways that affect cell behavior.

(Rac)-RK-682 is a racemic mixture that functions as a protein tyrosine phosphatases (PTPases) inhibitor, specifically targeting protein tyrosine phosphatase 1B (PTP-1B), low molecular weight protein tyrosine phosphatases (LMW-PTP), and cell division cycle 25B (CDC-25B), with inhibitory concentrations (IC50s) of 8.6 μM, 12.4 μM, and 0.7 μM, respectively [1].

Salubrinal, a phosphatases (PP1) inhibitor(IC50=1.7 μM), exhibits function on the eukaryotic translation initiation factor 2 subunit (eIF2α).

BCI ((E)-BCI) is an allosteric inhibitor of dual-specificity phosphatases (DUSP), with EC50 values of 13.3 μM for DUSP6 and 8.0 μM for DUSP1 in cells, and does not inhibit DUSP5.

Fosmanogepix (APX001) is a first-in-class, orally available broad-spectrum antifungal agent. It acts as an N-phosphonooxymethyl prodrug that undergoes rapid and complete metabolism by systemic alkaline phosphatases. This metabolism leads to the formation of the active moiety, APX001A. Fosmanogepix (APX001), with its ability to target the highly conserved Gwt1 fungal enzyme, holds great potential for the development of treatments against invasive fungal infections.

Tautomycin is a potent and specific protein phosphatases 1 and 2A inhibitor (Kiapp of 0.16 nM and 0.4 nM for PP1 and PP2A, respectively), and is an antifungal antibiotic isolated from the bacterium Streptomyces verticillatus.

NSC-87877 is an effective inhibitor of Shp2 and Shp1 protein tyrosine phosphatases (IC50=0.318 μM, 0.355 μM of shp2 and shp1, respectively).It also inhibits dual-specificity phosphatase 26 (DUSP26).

Okadaic acid is a potent polyether marine toxin that primarily accumulates in the digestive glands of marine mollusks. It is a highly effective and selective inhibitor of protein phosphatases (PPs). By inhibiting these phosphatases, okadaic acid increases the phosphorylation levels of various proteins, acts as a tumor promoter, and induces tau protein phosphorylation. It can be used to establish models of Alzheimer’s disease and skin cancer.

bpV(bipy) hydrate acts as an inhibitor for phosphoinositide 3-phosphatase (PTEN) and protein tyrosine phosphatases PTP-β and PTP-1B, with IC50 values of 18, 60.3, and 164 nM, respectively.

Bis(maltolato)oxovanadium(IV) (BMOV) is a potent, reversible, competitive, and orally active pan-PTP (protein tyrosine phosphatases) inhibitor with insulin-mimicking effects and anti-diabetic properties. BMOV is a potent insulin sensitizer and has been shown to improve cardiac dysfunctions in diabetic models. BMOV inhibits HCPTPA, PTP1B, HPTPβ, and SHP2 with IC50s of 126 nM, 109 nM, 26 nM, and 201 nM, respectively [1][2].

DiFMUP (6,8-Difluoro-4-methylumbelliferyl phosphate) inhibits protein tyrosine phosphatases (PTPs) and can be used to assay threonine phosphatase activity.

MurA-IN-1 (compound 1a), a PTPRR inhibitor, exhibits IC50 values of 0.09 μM for PTPRR, 0.23 μM for PTP1B, 0.75 μM for PTPN7, and 0.8 μM for PTPN5, respectively, targeting a family of human MAPK-specific protein tyrosine phosphatases[1].

Protein tyrosine phosphatases (PTPs) remove phosphate from tyrosine residues of cellular proteins. Reversible phosphorylation catalyzed by the coordinated actions of protein tyrosine kinases and phosphatases is key to the regulation of the signaling events that control cell growth and proliferation, differentiation, and survival or apoptosis, as well as adhesion and motility. RK-682, a bioactive compound originally isolated from the fermentation of Streptomyces sp. 88-682, is an inhibitor of the PTPs. It inhibits the phosphorylation of CD45 and VHR with IC50 values of 54 and 2 μM, respectively, and arrests cell cycle progress at the G1/S transition. It is also reported to inhibit heparanase (IC50 = 17 μM), an endo-β-D-glucuronidase involved in tumor cell invasion and angiogenesis. RK-682 (calcium salt) is a less soluble version of the free acid.

Chrysophanol triglucoside, an anthraquinone derivative obtained from Cassia obtusifolia, demonstrates inhibitory activity against protein tyrosine phosphatases 1B (PTP1B) and α-glucosidase, with half-maximal inhibitory concentration (IC50) values of 80.17 μM and 197.06 μM, respectively. This compound exhibits potential for diabetes research.

Okadaic acid ammonium salt is a marine toxin that acts as an inhibitor of protein phosphatases (PP), with the highest affinity for PP2A (IC50 = 0.1–0.3 nM), while also inhibiting PP1, PP3, PP4, and PP5, but not PP2C. By increasing the phosphorylation of various proteins, it functions as a tumor promoter and induces tau protein phosphorylation, commonly used to establish Alzheimer's disease models.

PTPN22-IN-1, detailed in WO2021007491A1 as compound L-1, is a potent PTPN22 inhibitor, demonstrating an IC50 of 1.4 μM and a Ki of 0.50 μM. This compound achieves over 7-10 fold selectivity against PTPN22 relative to comparable phosphatases and enhances antitumor immune responses.

3,5-Difluoro-L-tyrosine is a functional and tyrosinase-resistant tyrosine mimic, commonly used to evaluate the substrate specificity of protein tyrosine phosphatases (PTPs).

MLS-0437605 is a potent and selective inhibitor of dual-specificity phosphatase 3 (DUSP3), with an IC50 of 3.7 μM. It exhibits higher selectivity towards DUSP3 in comparison to DUSP22 and other protein tyrosine phosphatases (PTPs).

Microcystin-LR (Cyanoginosin-LR) is a potent inhibitor of type 1 and type 2A protein phosphatases (PP1 and PP2A), with IC50s of 1.7 nM and 0.04 nM, respectively.