PP1

PP1 (AGL 1872), a specific and effective Src inhibitor, is with IC50 for Lck Fyn is 5 nM 6 nM, respectively.

3BrB-PP1 is an ATP-competitive analog that exhibits specific inhibitory activity towards protein kinase, particularly effective against protein kinases with mutations in the ATP-binding pocket, such as the Thr97 mutation within Sty1's ATP-binding pocket.

1-NM-PP1 (PP1 Analog II) is a cell-permeable PP1 analog that acts as a potent and selective inhibitor of mutant kinases over their wild-type progenitors.

1-Naphthyl PP1 hydrochloride (1-NA-PP 1 hydrochloride) is a selective inhibitor of Src family kinases v-Src.

1-Naphthyl PP1 (1-NA-PP 1) is a selective Src inhibitor, targeting v-Src and c-Fyn, c-Abl, CDK2, and CAMK II with IC50 values of 1.0, 0.6, 0.6, 18, and 22 μM, respectively.

3MB-PP1 is a bulky purine analog and a Polo-like kinase 1 (Plk1) inhibitor. In cells expressing analog-sensitive Plk1 alleles, 3MB-PP1 blocks mitotic progression and cell division arise by targeting Plk1. 3MB-PP1 specifically inhibits analog-sensitive Ssn3 (Cdk8). 3MB-PP1 inhibits Leu93 Mutant Zipper-interacting protein kinase with IC50 of 2 μM. 3MB-PP1 can be used for the research of cell division and hypha formation of Candida albicans.

3-IN-PP1, a potent protein kinase D (PKD) inhibitor, exhibits pan-PKD inhibitory activity with IC50 values of 108 nM for PKD1, 94 nM for PKD2, and 108 nM for PKD3. Additionally, it serves as a broad-spectrum anticancer agent by inhibiting the growth of various tumor cells. 3-IN-PP1 is utilized in cancer research [1].

PP-121 is a multi-targeted inhibitor of PDGFR (IC50: 2 nM), Hck (IC50: 8 nM), mTOR (IC50: 10 nM), VEGFR2(IC50: 12 nM), Src (IC50: 14 nM) and Abl (IC50: 18 nM) , also inhibits DNA-PK (IC50: 60 nM).

HXJ42 is a PP1 analog that selectively and effectively acts on wild-type ZAP-70 (AS).

Ac-Ala-OH (N-Acetyl-L-alanine) is a substrate for Guanine nucleotide-binding protein G(I) G(S) G(O) gamma-2 subunit, Myelin basic protein, GTP-binding nuclear protein Ran, Tropomyosin alpha 4 chain, HIV-1 Rev binding protein 2, Xaa-Pro dipeptidase, Thymosin beta-10, Actin-like protein 3, Alanine aminotransferase, Serine threonine protein Phosphatase PP1-beta catalytic subunit,10 kDa heat shock protein (mitochondrial), Calmodulin and Beta-1-syntrophin.

2OH-BNPP1 is a BUB1 kinase, a Ser Thr kinase inhibitor, it used for the treatment of cancer.

Endothall is a protein phosphatase 2A (PP2A) inhibitor, capable of inhibiting PP2A (IC50: 90 nM) and PP1 (IC50: 5 uM). It acts as a herbicide and can also be useful in cancer chemotherapy.

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.

PP102, an antimicrobial peptide, exhibits activity against gram-positive bacteria, including B. subtilis (MIC: 25 µM), S. aureus (MIC: 13.3 µM), S. lutea (MIC: 63 µM), and B. pumilus (MIC: 23 µM) [1].

NPP1-IN-1 is a highly potent inhibitor of NPP enzymes, effectively inhibiting NPP1 with an IC 50 value of 0.15 μM and NPP3 with an IC 50 value of 40 μM [1].

Potent, selective peptide agonist for the neuropeptide Y Y5 receptor (IC50 values for inhibition of NPY binding to human Y5, Y1, Y2 and Y4 receptors are 0.24, 530, > 500, and 51 nM respectively, Ki at Y5 = 0.1 - 0.15 nM). Stimulates food intake in vivo.

PP113 is an antimicrobial peptide with activity against both Gram-negative and Gram-positive bacteria, exhibiting minimum inhibitory concentrations (MICs) of 73.3 µM for E. coli, 23.3 µM for B. subtilis, 13 µM for S. aureus, 16.7 µM for S. lutea, and 23.3 µM for B. pumilus [1].

DPP1-IN-1 hydrate, a DPP1 inhibitor (IC 50: 1.6 nM), exhibits excellent bioavailability and pharmacokinetic properties, making it suitable for investigating inflammatory diseases [1].

ENPP1 inhibitor C is an inhibitor of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1; IC50 = 0.26 μM in a cell-free assay).1 It is selective for ENPP1 over ENPP2-7 at 10 μM. ENPP1 inhibitor C decreases ENPP1 activity in MDA-MB-231 human breast and C6 rat glioma cancer cells when used at a concentration of 10 μM. |1. Kawaguchi, M., Han, X., Hisada, T., et al. Development of an ENPP1 fluorescence probe for inhibitor screening, cellular imaging, and prognostic assessment of malignant breast cancer. J. Med. Chem. 62(20), 9254-9269 (2019).

ENPP1 inhibitor 43 is a novel small molecule for cancer immunotherapy.

[cPP1-7,NPY19-23,Ala31,Aib32,Gln34]-hPancreatic Polypeptide is a potent and selective neuropeptide Y Y5 receptor agonist, exhibiting a binding affinity with an IC50 of 0.24 nM for the hY5 receptor, and significantly stimulates food intake [1].

PP13 is an antimicrobial peptide with efficacy against both Gram-negative and Gram-positive bacteria, displaying minimum inhibitory concentrations (MIC) of 16.7 µM for E. coli, 13.3 µM for B. subtilis, 23.3 µM for S. aureus, 8.0 µM for S. lutea, and 9.0 µM for B. pumilus [1].

DPP1-IN-1 (compound 1) serves as a potent DPP1 inhibitor and is utilized in the study of bronchiectasis [1].

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.

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

Cytostatin is a natural antitumor inhibitor of cell adhesion to extracellular matrix, blocking adhesion of B16 melanoma cells to laminin and collagen type IV in vitro (IC50s = 1.3 and 1.4 μg/ml, respectively) and B16 cells metastatic activity in mice. It induces apoptosis of FS3 mouse fibrosarcoma cells (IC50 = 3.1 μg/ml). Cytostatin potently and selectively inhibits protein phosphatase 2A (PP2A; IC50 = 29 nM against the catalytic subunit), while having no effect against PP1, PP2B, or PP5.

EBOV-IN-C31 is a novel PP1-targeting Ebola Virus (EBOV) inhibitor with improved pharmacological properties.

Cantharidin imide is a PP1/2A inhibitor found in Canarthis vesicatoria. It inhibits proliferation of colorectal cancer cells, increases MCP-1, IL-6, and IL-β levels, and inhibits differentiation and resorptive activity of osteoclasts. This compound can produce severe skin inflammation, and is extremely toxic if ingested orally.

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.

1E7-03 is an inhibitor of HIV-1 transcription, by targeting host Protein Phosphatase-1 (PP1).

Cytostatin (sodium salt) is a natural antitumor inhibitor of cell adhesion to extracellular matrix, blocking adhesion of B16 melanoma cells to laminin and collagen type IV in vitro (IC50s = 1.3 and 1.4 μg/ml, respectively) and B16 cells metastatic activity in mice. It induces apoptosis of FS3 mouse fibrosarcoma cells (IC50 = 3.1 μg/ml). Cytostatin (sodium salt) potently and selectively inhibits protein phosphatase 2A (PP2A; IC50 = 29 nM against the catalytic subunit), while having no effect against PP1, PP2B, or PP5.

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.

Selective inhibitor of Ca2+-calmodulin-dependent protein phosphatase (calcineurin) (IC50 ~ 10 μM). Does not inhibit PP1, PP2A or CaM kinase II (IC50 > 100 mM).

Fostriecin (free base) is an inhibitor of the serine/threonine protein phosphatases 2A (PP2A) and 4 (PP4) (IC50s = 3.2 and 3 nM, respectively). It less effectively inhibits topoisomerase II and PP1 (IC50s = 40 and 131 μM, respectively) and does not inhibit PP2B. Through its effects on protein phosphatases, fostriecin increases the level of histone H3 phosphorylation and may alter epigenetic regulation of cell proliferation. On a related note, fostriecin was first identified as an antitumor antibiotic.

Okadaic acid ammonium salt, a marine toxin, serves as an inhibitor of protein phosphatases (PP), displaying a higher affinity for PP2A (IC50 = 0.1-0.3 nM) alongside inhibitory effects on PP1 (IC50 = 15-50 nM), PP3 (IC50 = 3.7-4 nM), PP4 (IC50 = 0.1 nM), and PP5 (IC50 = 3.5 nM), but does not affect PP2C. By inhibiting PPs, this compound promotes protein phosphorylation, acts as a tumor promoter, and is involved in inducing tau phosphorylation.

Okadaic acid is a potent polyether marine toxin that accumulates in the digestive glands of marine mollusks.Okadaic acid is a highly potent and selective protein phosphatase (PP) inhibitor, inhibiting PP1, PP2A, PP3, PP4, and PP5.Okadaic acid activates Wnt β-catenin signaling in human HepaRG cells. catenin signaling in human HepaRG cells.