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-(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.

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].

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].

(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).

PKA Regulatory Subunit II Substrate (RII phosphopeptide) is a tool peptide derived from the regulatory subunit Type II (RII) of cyclic adenosine monophosphate-dependent protein kinase (PKA). It is commonly used to simulate the phosphorylation activity of protein kinases and to assess the activity of protein phosphatases by serving as a specific substrate.

Suramin is a dual-function inhibitor of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and protein tyrosine phosphatases (PTPases), with antiparasitic, anticancer, and anti-angiogenesis properties, inhibiting sirtuins and DNA topoisomerase II.

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

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.

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.

RK-682 is a natural selective inhibitor of protein tyrosine phosphatases (PTPases).

BML-260 is a potent dual-specificity inhibitor of the phosphatases JSP-1 and DUSP22. It can activate UCP1 and induce thermogenesis in adipocytes independently of JSP-1. The effects of BML-260 on adipocytes partially occur through the activation of the CREB, STAT3, and PPAR signaling pathways. This compound is useful for research on inflammation, proliferative disorders associated with JNK signaling dysfunction, and obesity.

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.

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.

Lockdown is a reversible and non-competitive PPM1F inhibitor. Lockdown is selective for PPM1F, because this compound does not inhibit other protein phosphatases in vitro and does not induce additional phenotypes in PPM1F knockout cells. Lockdown acts in a dose-dependent, allosteric manner with high selectivity for PPM1F

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.

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.

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.

Phenytoin-d10 is intended for use as an internal standard for the quantification of phenytoin by GC- or LC-MS. Phenytoin is an anticonvulsant agent and active metabolite of fosphenytoin. Phenytoin is formed from fosphenytoin by tissue phosphatases. It inhibits neuronal voltage-gated sodium channels in a voltage-dependent manner. Phenytoin reduces the neuronal firing frequency and decreases the amplitude of excitatory post-synaptic potentials (EPSPs) in electrically stimulated rat corticostriatal slices. It protects against seizures induced by maximal electroshock (MES) in mice. Formulations containing phenytoin have been used in the treatment of tonic-clonic seizures and status epilepticus.

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).