Phosphatase-IN-1

Phosphatase-IN-1 (compound II-8), a propranolol derivative, acts as an inhibitor of phosphatidate phosphatase (Pah). It binds to MoPah1 with an affinity constant of 19.8 μM, demonstrating growth inhibition of plant pathogens and anti-fungal properties, while exhibiting no toxicity towards rice seedlings and wheat heads [1].

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.

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.

Calcium glycerophosphate(CaGP) is an inhibitor of intestinal alkaline phosphatase F3. Calcium glycerophosphate can be a source of calcium and phosphorus in total parenteral nutrition solutions [1] [2].

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].

Calyculin A ((-)-Calyculin A), a toxicant in the Japanese marine sponge CDiscodermia calyxC, is a selective and potent inhibitor of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), inducing hyperactivation of cryopreserved bovine spermatozoa and inhibiting radiation-induced gammaH2AX DNA repair disease in human lymphocytes. gammaH2AX DNA repair foci in human lymphocytes.

TT2-32 TFA induces a biphasic activation of phosphotyrosine phosphatase activity in human colon tumor cell line, SW620

PTP1B-IN-1 (PTP1B inhibitor) is a potent inhibitor of protein tyrosine phosphatase 1B (PTP1B) (IC50 : 1.6 mM)

Icerguastat (IFB-088) is a selective inhibitor of holophosphatase. Sephin1 safely and selectively inhibited a regulatory subunit of protein phosphatase 1 in vivo.

LTV-1 has the potential for autoimmunity treatment. LTV-1 is a potent lymphoid tyrosine phosphatase (LYP) inhibitor in T cells with an IC50 of 508 nM.

SHIP2-IN-1 is a potent SHIP2 inhibitor (IC50: 2 µM) used in Alzheimer's disease research.

AS1949490 activated glucose metabolism via up-regulation of GLUT1 gene in L6 myotubes[1][2]. AS1949490 is a potent and selective SHIP-2 (SH2 domain-containing inositol 5′ phosphatase 2) inhibitor, with an IC50 of 620 nM.

HDHD4-IN-1 (compound 3) is an inhibitor of N-acetylneuraminate-9-phosphate phosphatase (HDHD4) with an IC50 value of 11 μM. It is utilized in the research of neurological disorders.

TNAP-IN-1 is a specific inhibitor of tissue-nonspecific alkaline phosphatase (TNAP) and is utilized in studying diseases related to soft tissue calcification.

VHR-IN-1 (Compound SA1) is an effective and selective VHR phosphatase inhibitor with an IC50 of 18 nM. It hinders the proliferation of cervical cancer cells, demonstrating antitumor activity.

SMAPP1 is an activator of protein phosphatase 1 (PP1). SMAPP1 induces PP1 activity in vitro and activates latent HIV-1 provirus in cultured and primary T cells.

α-D-Glucose-1,6-bisphosphate is abis-phosphorylated derivative of α-D-glucose that has roles in carbohydrate metabolism.1It is the product of the reaction of glucose-1- or 6-phosphate with glucose-1,6-bisphosphate synthase (PGM2LI) in the conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate.2It is also a cofactor for the bacterial enzyme phosphopentomutase.3,4α-D-Glucose-1,6-bisphosphate has been used in the study of carbohydrate metabolism. 1.Beitner, R.Regulation of carbohydrate metabolism by glucose 1,6-bisphosphate in extrahepatic tissues; comparison with fructose 2,6-bisphosphateInt. J. Biochem.22(6)553-557(1990) 2.Maliekal, P., Sokolova, T., Vertommen, D., et al.Molecular identification of mammalian phosphopentomutase and glucose-1,6-bisphosphate synthase, two members of the α-D-phosphohexomutase familyJ. Biol. Chem.282(44)31844-31851(2007) 3.Moustafa, H.M.A., Zaghloul, T.I., and Zhang, Y.-H.P.A simple assay for determining activities of phosphopentomutase from a hyperthermophilic bacterium Thermotoga maritimaAnal. Biochem.50175-81(2016) 4.Panosian, T.D., Nannemann, D.P., Watkins, G.R., et al.Bacillus cereus phosphopentomutase is an alkaline phosphatase family member that exhibits an altered entry point into the catalytic cycleJ. Biol. Chem.286(10)8043-8054(2011)

The cyanobacterium Nodularia spumigena often contaminates the drinking water of rural communities in developing countries and accumulates in mussels, flounder, and cod from the northern Baltic Sea. Nodularin is a hepatotoxic monocylic pentapeptide produced by the N. spumigena. It is a potent inhibitor of protein phosphatase types 1 (PP1) and 2A (PP2A), exhibiting IC50 values of 1.8 and 0.026 nM, respectively. PP2B is inhibited to a lesser extent with an IC50 of 1.8 μM. No apparent inhibitory effect is observed with PP2C, alkaline phosphatase, acid phosphatase, insulin receptor tyrosine kinase, protein kinase A, phosphorylase kinase, or protein kinase C.

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.

D-myo-Inositol-4-phosphate (Ins(4)P1) is a member of the inositol phosphate (InsP) molecular family that play critical roles as small, soluble second messengers in the transmission of cellular signals. The most studied InsP, Ins(1,4,5)P3, is a second messenger produced in cells by phospholipase C (PLC)-mediated hydrolysis of phosphatidylinositol-4,5-diphosphate. Binding of Ins(1,4,5)P3 to its receptor on the endoplasmic reticulum results in opening of the calcium channels and an increase in intracellular calcium. Ins(4)P1 can be formed by dephosphorylation of Ins(1,4)P2 by inositol polyphosphate 1-phosphatase or dephosphorylated to inositol by inositol monophosphatase.

Darinaparsin is a dimethylated arsenic linked to glutathione. It is cytotoxic to DU145, LNCaP, and PC3 prostate cancer cells (IC50s = 5-10 µM) and patient-derived primary prostate cancer cells (IC50s = 2.5-20 µM), as well as Jurkat T cell lymphoma and L540 Hodgkin lymphoma cells (IC50s = 2.7 and 1.3 µM, respectively). [1][2] It decreases the tumor-initiating subpopulation in DU145 and PC3 cells and halts the cell cycle in the G2 M phase. Darinaparsin decreases transcription of Gli-2, a transcription factor that mediates Sonic hedgehog signaling, when used at a concentration of 1.5 but not 3 µM. It decreases SHP1 phosphatase activity and increases ERK phosphorylation. [2] Darinaparsin reduces tumor growth in DU145 and PC3 prostate cancer mouse xenograft models when administered at a dose of 100 mg kg every other day.[1]

D-myo-Inositol-1,3-phosphate (Ins(1,3)P) is a member of the inositol phosphate (InsP) molecular family that play critical roles as small, soluble second messengers in the transmission of cellular signals. The most studied InsP, Ins(1,4,5)P3 is a second messenger produced in cells by phospholipase C (PLC)-mediated hydrolysis of phosphatidylinositol-4,5-biphosphate. Binding of Ins(1,4,5)P3 to its receptor on the endoplasmic reticulum results in opening of the calcium channels and an increase in intracellular calcium. Ins(1,3)P2 can be dephosphorylated to Ins(1)P by inositol polyphosphate 3-phosphatase and further dephosphorylated to inositol by inositol monophosphatase.

PTP1B-IN-3 diammonium is a highly effective and orally bioavailable inhibitor of the protein tyrosine phosphatase 1B (PTP1B) enzyme, with an IC50 value of 120 nM for both PTP1B and TCPTP, exhibiting potent antidiabetic and anticancer properties, as supported by extensive research [1] [2].

AQX-435 is a potent activator of SHIP1 (SH2 domain-containing inositol-5′-phosphatase 1). AQX-435 decreases B-cell receptor (BCR) downstream PI3K activity, induces apoptosis in malignant B cells, and exhibits inhibitory effects on lymphoma growth.