Phosphatase

Osunprotafib (ABBV-CLS-484) is a potent, orally bioavailable PTP1B PTPN2 inhibitor in clinical trials for solid tumors. [1] Osunprotafib (ABBV-CLS-484) stimulates the tumor microenvironment and promotes natural killer cell and CD8 T cell function and enhances T cell anti-tumor immunity by enhancing JAK-STAT signaling and reducing T cell dysfunction. [2]

Ertiprotafib (PTP 112), a selective and potent inhibitor of protein tyrosine phosphate 1B (PTP1B) and IkappaB kinase β (IKK-β), is a novel insulin sensitizer with potential anticancer activity for the study of type 2 diabetes and breast cancer.

SHP099 (SHP099 free base) free base is an effective, selective, orally bioavailable, and efficacious SHP2 inhibitor (IC50 =0.07 μM and p-ERK modulation in cells IC50 = 0.250 μM). SHP099 shows dose-dependent pathway inhibition and antitumor activity in xenograft models.

Cyclosporin A is a naturally occurring cyclic polypeptide that is the active metabolite of a fungus. Cyclosporin A is an immunosuppressant that binds to procyclins and inhibits calcineurin (IC50=7 nM).

Razuprotafib (AKB-9778) is a protein tyrosine phosphatase ß (HPTPß) inhibitor with an IC50 of 50 nM. It effectively activates Tie-2 and provides protection against acute kidney injury.

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.

TNO155 is a protein tyrosine phosphatase (PTP) non-receptor type 11 (SHP2; src homology region 2 domain phosphatase; PTPN11) inhibitor(IC50 : 0.011 µM),with potential antineoplastic activity.

RMC-4630 (SHP2-IN-7) is an inhibitor of SHP2.

Tacrolimus (Fujimycin) can bind FKBP12 to form a high-affinity complex (Ki: 0.2 nM) which inhibits the activity of the calcium calmodulin-dependent protein phosphatase.

Cyclosporine is a calcineurin phosphatase pathway inhibitor, used as an immunosuppressant drug to prevent rejection in organ transplantation.

SHP099 hydrochloride is a potent, selective, orally bioavailable SHP2 inhibitor with IC50 of 70 nM, which inhibits ERK1 2 activation in cancer cells. [2]

PTP1B-IN-3 is a selective and potent PTP1B inhibitor with anticancer activity that inhibits PTP1B and TCPTP.PTP1B-IN-3 is used in the study of diabetes.

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.

CDP-Star is a luminescent substrate for 1,2-dioxetane and a substrate for alkaline phosphatase.CDP-Star can be used for in vivo imaging by detecting mRNA on Northern blot.

Ebselen (CCG-39161) is a organoselenium compound with anti-inflammatory, anti-oxidant and cytoprotective activity. Ebselen acts as a glutathione peroxidase mimetic and is thereby able to prevent cellular damage induced by reactive oxygen species (ROS). In addition, this agent inhibits the activity of a variety of enzymes including nitric oxide synthase (NOS), 5-lipoxygenase, cyclooxygenase, protein kinase C (PKC), NADPH oxidase and gastric H+ K+-ATPase. Furthermore, ebselen may be neuroprotective due to its ability to neutralize free radicals upon NMDA receptor activation thus, reducing lipoperoxidation mediated by glutamate-induced excitotoxicity.

LB100 (LB-100) is a water soluble protein phosphatase 2A (PP2A) inhibitor.

MY10, a potent and orally active inhibitor of the receptor protein tyrosine phosphatase (RPTPβ ζ), effectively reduces binge-like ethanol consumption and diminishes the rewarding effects of ethanol.

CaMKP Inhibitor can inhibit CaMKP.

SC-43 is a potent and orally active agonist of SHP-1 (PTPN6). SC-43 inhibits the phosphorylation of STAT3 and induces cell apoptosis, and with anti-fibrotic and anticancer effects.

MB-07729 is a potent non-competitive inhibitor of fructose-1,6-bisphosphate with IC50 values of 189, 121 and 31 nM in rat, monkey and human, respectively, for the study of diabetes.

Voclosporin (ISAtx-247) is a novel, orally available calcium-modulated phosphatase (CN; PP2B) inhibitor and immunosuppressant used for treating lupus nephritis.

Vutiglabridin (HSG4112) is a novel and safe modulator of PON2, a racemic compound. vutiglabridin is an optimized structural analogue of Glabridin and is superior to Glabridin in terms of weight loss and chemical stability. vutiglabridin ameliorates mptp-induced neurodegeneration in Parkinson's disease mice by targeting mitochondrial paraoxonase-2. Vutiglabridin is a clinical phase 2 drug for the treatment of obesity and has therapeutic effects on p-mitochondrial PON2 in a PD model. vutiglabridin penetrates the brain, binds PON2, and restores 1-methyl-4-phenylpyridine (MPP*)-induced neuroblastoma in SH-SY5Y Vutiglabridin significantly attenuated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dyskinesia and dopaminergic neuronal damage in mice modeled with PD in mouse experiments.

β-Glycerophosphate is a classical serine-threonine phosphatase inhibitor used in kinase reaction buffers. BGP is often used in combination with other phosphatase protease inhibitors for broad spectrum inhibition. It functions as an organic phosphate donor

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].

7-BIA is a receptor-type protein tyrosine phosphatase D (PTPRD) inhibitor with anti-addictive properties, and is utilized in neuropathic pain research.

D-erythro-Sphingosine (trans-4-Sphingenine) is a protein kinase C (PKC) inhibitor. D-erythro-Sphingosine (Erythrosphingosine) is also a PP2A activator

BTdCPU is a potent activator of heme-regulated eIF2α kinase (HRI) . BTdCPU promotes eIF2α phosphorylation and induced apoptosis in resistant cell.

Cyt-PTPε Inhibitor-1 (A Inhibitor-1) is an inhibitor of cytosolic protein tyrosine phosphatase ε. Cyt-PTPε Inhibitor-1 blocks the dephosphorylation of c-Src and exhibits anti-osteoclastic activity.

Mulberrofuran G, isolated from Morus alba L., has anti-hepatitis B virus activity and protects against ischemic injury-induced cell death. Mulberrofuran G is a dual inhibitor of PTP1B and alpha-glucosidase for use in the study of Alzheimer's disease.

Lupenone is a natural product isolated from Rhizoma Musae and has good anti-diabetic activity,and has anti-inflammatory activity.lupenone were potent PTP1B inhibitors with IC50 values of 15.11±1.23μM.

DA-3003-1 (DA-3003-1) is a membrane-permeable, potent and selective Cdc25 dual specificity phosphatase inhibitor with antitumor activity that inhibits Cdc25B2, Cdc25A, Cdc25B2 and Cdc25C.

CX08005 is a protein tyrosine phosphatase 1B inhibitor. CX08005 reduces hepatic lipid accumulation and microcirculatory impairment associated with non-alcoholic fatty liver disease.

Tegeprotafib (PTPN2 1-IN-1) is an orally active and potent PTPN1 2 inhibitor with potential anticancer and antitumor activity for the study of cancer and immune system diseases.

1. Kuwanon G (Moracenin B) as dual inhibitors of PTP1B and α-glucosidase enzymes, as well as insulin sensitizers, it may potentially be utilized as an effective treatment for Type II diabetes mellitus. 2. Kuwanon G has anti-inflammatory activity, it can attenuate atherosclerosis through inhibiting foam cell formation and inflammatory response. 3. Kuwanon G is a potent inhibitor of Mycobacterium tuberculosis protein tyrosine phosphatase B. 4. Kuwanon G shows acetylcholinesterase (AChE) and butyrylcholinesterase(BChE) inhibitory activities, it may be a promising candidate for preventive and therapeutic agents for Alzheimer's disease. 5. Kuwanon G prevents the pathological progression of allergic asthma through the inhibition of lung destruction by inflammation and immune stimulation. 6. Kuwanon G has antibacterial activity against oral pathogens. 7. Kuwanon G is a specific antagonist for the GRP-preferring receptor and can be useful for studying the physiological and pathological role of GRP.

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

β-Glycerophosphate disodium salt pentahydrate is a protein phosphatase inhibitor.

NSC 95397 is a potent inhibitor of Cdc25 dual specificity phosphatase(Ki of 32, 96, and 40 nM for Cdc25A, Cdc25B, and Cdc25C, respectively).

1. Stearic acid (Cetylacetic acid) can reduce metastatic tumor burden. 2. Stearic acid leads to dramatically reduced visceral fat likely by causing the apoptosis of preadipocytes. 3. Stearic acid and its derivatives have been used as gelators in food and pharmaceutical gel formulations. 4. Stearic acid is a potent phosphatase 1B inhibitor, possibly causing an enhancement in the insulin receptor signaling to stimulate glucose uptake into adipocytes. 5. Stearic acid has the potential to increase dry matter intake and yields of milk and milk components, without affecting conversion of feed to milk, body condition score, or body weight.

TPI-1 is a SHP-1 inhibitor.

Rosiptor (AQX-1125) (AQX-1125) is an orally-active and specific phosphatase SHIP1 activator with anti-inflammatory effects.

Azoxystrobin (Bankit) is a broad-spectrum fungicide. Azoxystrobin induces ROS production, cell apoptosis and mitochondrial respiration by blocking electron transfer between cytochromes b and c1.

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.

Sephin1 (IFB-088) is reportedly a selective inhibitor of GADD34 (PPP1R15A), which is a stress-induced regulatory subunit of protein phosphatase 1 complex that dephosphorylates eIF2α

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).

CDC25B-IN-1 is an inhibitor of CDC25B with a Ki of 8.5 μM. CDC25B-IN-1 increases the G2 M phase by inhibiting cell proliferation and colony formation.

BVT948 is a protein tyrosine phosphatase (PTP) inhibitor that also inhibits lysine methyltransferase SETD8 (KMT5A) and various cytochrome P450 (P450) isoforms.

RMC-4550 is an effective and allosteric inhibitor of SHP2 (IC50: 0.583 nM).

N-Stearoylsphingosine (Cer(d18:1 18:0)) is an amide compound widely found in eukaryotic organisms that enhances protein phosphatase 2A (PP2A) activity by interfering with the binding of PP2A to PP2A inhibitor 2, leading to dephosphorylation of Akt.N-Stearoylsphingosine is used in prostate cancer research.