pp2a

PP2A Cancerous-IN-1 is a potent inhibitor of CIP2A (Cancerous inhibitor of PP2A) and p-Akt, demonstrating significant anti-proliferative effects.

MKI-1 (MASTL Kinase Inhibitor-1) is an inhibitor of MASTL (microtubule-associated serine threonine kinase-like, IC50= 9.9 μM). MKI-1 exerts radiosensitizer and antitumor activities through PP2A activation in breast cancer.

DT-061, an orally bioavailable protein phosphatase 2A (PP2A) activator, may be used in the therapy of KRAS-mutant and MYC-driven tumorigenesis.

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.

TPP2a is a mitochondrial thioredoxin reductase (TrxR) inhibitor.

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.

LB-100, a novel Protein Phosphatase 2A (PP2A) inhibitor, sensitizes malignant meningioma cells to the therapeutic effects of radiation

Ethoxysanguinarine (6-Ethoxydihydrosanguinarine) shows human blood acetylcholinesterase (HuAChE) and human plasma butyrylcholinesterase (HuBuChE) inhibitory activity, with IC50 values of 0.83 +/- 0.04 microM and 4.20 +/- 0.19 microM, respectively.

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

AMZ30 is a selective inhibitor of PME-1 (IC50: 600 nM). It also reduces the demethylated form of PP2A in living cells.

IQ 1 has multiple roles, such as maintaining the multifunctionality of mouse ESCs, decreasing Wnt-stimulated phosphorylation, blocking PP2A/Nkd interactions, and so on.

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

TD52 dihydrochloride (TD52 2HCl), a derivative of Erlotinib, is a potent and orally active inhibitor of protein phosphatase 2A (CIP2A). It exhibits strong anti-cancer properties by regulating the CIP2A PP2A p-Akt signaling pathway, resulting in the induction of apoptosis in triple-negative breast cancer (TNBC) cells. Mechanistically, TD52 dihydrochloride disrupts the binding of Elk1 to the CIP2A promoter, effectively reducing CIP2A levels. Notably, TD52 dihydrochloride demonstrates powerful anti-cancer activity while displaying less inhibition of p-EGFR.

TAT-PDHPS1 is a peptide inhibitor targeting Yes-associated protein (YAP) signaling, composed of the endogenous peptide PDHPS1 and the cell-penetrating peptide sequence TAT. It operates by binding to protein phosphatase 2 phosphatase activator (PTPA), thereby activating protein phosphatase 2A (PP2A). This activation precipitates the phosphorylation of YAP, culminating in the suppression of genes targeted by YAP. Demonstrated to inhibit the proliferation of ovarian cancer cells in vitro and reduce ovarian tumor growth in a subcutaneous xenograft mouse model, TAT-PDHPS1 presents a potent approach to managing ovarian malignancies.

FTY720-Mitoxy is an FTY720 analog that can be uesd as a novel stimulator of the activity of the protein phosphatase 2A (PP2A), targeting mitochondria.

ATUX-1215, a protein phosphatase 2A (PP2A) activator, diminishes the phosphorylation of ERK, p38, JNK, and Akt, as well as decreases the secretion of IL-12p70, GM-CSF, and IL1α in BLM-treated animals, potentially decelerating lung fibrosis progression [1].

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.

Rubratoxin A is a classical mycotoxin used as a PP2A-specific inhibitor.

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.

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.

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.

(1S,2S,3R)-DT-061, an enantiomer of DT-061, is an orally bioavailable activator of PP2A.

TD52 is an orally active inhibitor of cancerous inhibitor of PP2A (CIP2A). TD52 is an Erlotinib derivative and indirectly reduced CIP2A by disturbing Elk1 binding to the CIP2A promoter.

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

Microcystin LA, a natural toxin, exerts its cytotoxic effects by inhibiting the serine-threonine protein phosphatases PP1 and PP2A with IC50s of 0.3 and 0.3 nM, respectively.

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.

Trichosanatine and squamosamide, as potential candidates as lead compounds for further study in drug development process with the PP2A- α protein. Trichosanatine can alleviate oxidized low-density lipoprotein induced endothelial cells injury via inhibiting the LOX-1/p38 MAPK pathway.

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.

Growth hormone releasing peptide ia a natual product ,and has anti-inflammatory effects, due to its inhibitory effect on PKC-induced activation of p38, JNK and NF-κB, possibly by targeting to MKP-1 and PP2A.

SMAP-2 is an orally bioavailable activator of phosphatase 2A (PP2A) which binds to the PP2A Aα scaffold subunit to drive conformational changes in PP2A. It inhibits the growth of KRAS-mutant lung cancers .

MP07-66 is a novel FTY720-analog devoid of immunosuppressive effects leads to the reactivation of PP2A, which in turn triggers apoptosis of CLL cells.

ITH12711, a PP2A ligand, can traverse the blood-brain barrier (BBB) and exerts neuroprotection by restoring PP2A-phosphatase activity [1].

(Rac)-LB-100, the racemic form of LB-100, functions as an inhibitor of protein phosphatase 2A (PP2A) [1].

TRC-766, a negative control of RTC-5 (TRC-382), is a compound that exhibits protein phosphatase 2A (PP2A) binding properties while lacking phosphatase activation capabilities.

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.