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].

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

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.

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.

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.

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.

STF-1084 is an inhibitor that cannot penetrate cells and targets ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (ENPP1) with an apparent Ki of 0.11 µM. It demonstrates selectivity for ENPP1 over ENPP2 and alkaline phosphatase (ALP) with apparent Kis of 5.5 and >100 µM, respectively, and does not affect a panel of 468 kinases at 1 µM. STF-1084 hinders the extracellular breakdown of cGAMP in ENPP1-overexpressing and cGAS-expressing 293T cells, with an IC50 of 0.340 µM, and enhances mRNA expression for the gene encoding IFN-β in CD14+ primary human peripheral blood mononuclear cells (PBMCs) when incubated with conditioned medium from ENPP1-overexpressing and cGAS-expressing 293T cells treated with STF-1084. In a live setting, STF-1084, when combined with ionizing radiation, elevates the proportion of tumor-associated CD11c+ cells among antigen-presenting cells (APCs) in a murine mammary cancer model (4T1).

ALP-IN-1 (Compound 7e) is an inhibitor of alkaline phosphatase (ALP) with an IC50 value of 0.308 µM.

PTP1B-IN-27 (Compound 7i) is an inhibitor of protein tyrosine phosphatase 1-B (PTP-1B) with an IC50 of 8.2 µM. Additionally, it inhibits α-glucosidase with an IC50 of 120 µM and exhibits competitive inhibition characteristics (Ki=118 µM).

Cantharidic acid is a selective inhibitor of protein phosphatase 2 (PP2A) and protein phosphatase 1 (PP1). It impedes cell viability by upregulating the ERK1/2, p38, and JNK1/2 pathways, causes cell cycle arrest at the sub-G1 phase, and induces apoptosis in NPC-39 and HONE-1 cells.

SHOC2–RAS PPI-IN-1 (compound 6) is a non-covalent competitive inhibitor that targets the interaction between SHOC2 and RAS proteins. It exhibits an IC50 of 0.048 μM and a KD of 0.065 μM against NRASQ61R. This compound inhibits SMP phosphatase-complex activity, increasing CRAFS259 phosphorylation levels and thus blocking the MAPK signaling pathway (by reducing pMEK and pERK levels). It induces cell cycle arrest and apoptosis in tumor cells. SHOC2–RAS PPI-IN-1 is used in targeting studies for malignancies, such as NRASQ61R-mutant melanoma and colorectal cancer.

ACP3 ligand 1 (Compound I11a) is a ligand targeting acid phosphatase 3 (ACP3, ACPP). It interacts with tumor cells expressing ACP3 on their surface and is used for drug delivery applications in vivo.

CA-II/TNAP-IN-1 is a novel 1,3-disubstituted thiourea derivative that acts as a dual inhibitor of carbonic anhydrase II (CA-II) and tissue-nonspecific alkaline phosphatase (TNAP). The compound is an essential tool for investigating cancer metabolism and enzyme-mediated tumor microenvironment regulation, aiming to enhance anti-tumor efficacy by jointly inhibiting key enzymes involved in pH regulation and mineralization.

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

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.