Phosphatase Inhibitor

Tacrolimus (FK506), a molecular glue, a macrocyclic lactone, binds to FK506 binding protein (FKBP) to form a complex. Tacrolimus inhibits calcineurin phosphatase, which inhibits T-lymphocyte signal transduction and IL-2 transcription. Immunosuppressive properties.

β-Glycerophosphate disodium salt pentahydrate is a bioactive endogenous metabolite and a phosphatase inhibitor. β-Glycerophosphate disodium salt pentahydrate plays an important role in inducing and maintaining osteoblast differentiation, mineral metabolism and signal transduction, and can be used as a drug carrier to form heat-sensitive hydrogels. β-Glycerophosphate disodium salt hydrate accelerates the calcification of vascular smooth muscle cells.

Okadaic acid, a marine toxin, is an inhibitor of protein phosphatases (PP). Okadaic acid has a significantly higher affinity for PP2A (IC₅₀=0.1-0.3 nM), and inhibits PP1 (IC₅₀=15-50 nM), PP3 (IC₅₀=3.7-4 nM), PP4 (IC₅₀=0.1 nM), PP5 (IC₅₀=3.5 nM), but does not inhibit PP2C. Okadaic acid increases of phosphorylation of a number of proteins by inhibiting PP, and acts a tumor promoter. Okadaic acid induces tau phosphorylation.

Sodium orthovanadate is an inhibitor of protein tyrosine phosphatases, alkaline phosphatases and a number of ATPases, most likely acting as a phosphate analogue.

BBO-11818 is an orally active, highly selective (relative to NRAS and HRAS), non-covalent pan-KRAS inhibitor (IC₅₀=28-120 nM). BBO-11818 specifically binds to the Switch-II/Helix 3 pocket, disrupts the KRAS:RAF1 interaction by inducing conformational changes, and blocks the MAPK signaling pathway. BBO-11818 exhibits significant anti-tumor activity, which not only inhibits cell proliferation and induces apoptosis, but also drives tumor regression in xenograft models. BBO-11818 produces synergistic effects when combined with Cetuximab (HY-P9905), anti-PD-1 antibody or PI3Kα inhibitor. BBO-11818 is used in the research of KRAS mutation-related malignancies such as pancreatic cancer, non-small cell lung cancer and colorectal cancer.

(E)-2-Octenal is an Antifungal agent. (E)-2-Octenal disrupts cell membrane integrity and causes ROS accumulation. (E)-2-Octenal decreases the activities of phosphofructokinase and pyruvate kinase. (E)-2-Octenal inhibits Neofusicoccum parvum growth by disrupting mitochondrial energy metabolism. (E)-2-Octenal suppresses the growth of a Prochloraz (HY-B0845)-resistant Penicillium italicum strain. (E)-2-octenal exerts a broad-spectrum and potent inhibitory effect on various fungi, including Sclerotium rolfsii, Metarhizium anisopliae sensu lato, and Aspergillus flavus, etc. (E)-2-Octenal can be used for the research of citrus blue mold and mango stem-end rot.

Razuprotafib (AKB-9778) sodium is a potent and selective inhibitor of the catalytic activity of VE-PTP (vascular endothelial protein tyrosine phosphatase) with an IC₅₀of 17 pM. Razuprotafib sodium promotes TIE2 activation, enhances ANG1-induced TIE2 activation, and stimulates phosphorylation of signaling molecules in the TIE2 pathway, including AKT, eNOS, and ERK. Razuprotafib sodium inhibits the structurally related phosphatase PTP1B with an IC₅₀ of 780 nM. Razuprotafib sodium shows excellent selectivity for VE-PTP versus a variety of phosphatases, with the exception of HPTPη (IC₅₀=36 pM) and HPTPγ (100 pM).

Suramin sodium salt (Suramin hexasodium salt) is a reversible and competitive protein-tyrosine phosphatases (PTPases) inhibitor. Suramin sodium salt is a potent inhibitor of sirtuins: SirT1 (IC₅₀=297 nM), SirT2 (IC₅₀=1.15 μM), and SirT5 (IC₅₀=22 μM). Suramin sodium salt is a competitive inhibitor of reverse transcriptase (DNA topoisomerase II: IC₅₀=5 μM). Suramin sodium salt is a potent SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibitor. Suramin sodium salt efficiently inhibits IP5K and is an antiparasitic, anti-neoplastic and anti-angiogenic agent.

Ebselen (SPI-1005), a glutathione peroxidase mimetic, is a potent voltage-dependent calcium channel (VDCC) blocker. Ebselen potently inhibits M^pro (IC₅₀=0.67 μM) and COVID-19 virus (EC₅₀=4.67 μM).Ebselen is an inhibitor of HIV-1 capsid CTD dimerization. Ebselen, an organoselenium compound, can permeate the blood-brain barrier and has anti-inflammatory, antioxidant and anticancer activity.

Salubrinal is a cell-permeable and selective inhibitor of eIF2α dephosphorylation. Salubrinal acts as a dual-specificity phosphatase 2 (Dusp2) inhibitor and suppresses inflammation in anti-collagen antibody-induced arthritis. Salubrinal has antiviral activity against HSV-1 and inhibits dephosphorylation of eIF2α mediated by the HSV-1 protein ICP34.5.

β-Glycerophosphate disodium salt pentahydrate is a bioactive endogenous metabolite and a phosphatase inhibitor. β-Glycerophosphate disodium salt pentahydrate plays an important role in inducing and maintaining osteoblast differentiation, mineral metabolism and signal transduction, and can be used as a drug carrier to form heat-sensitive hydrogels. β-Glycerophosphate disodium salt hydrate accelerates the calcification of vascular smooth muscle cells.

SHP099 is an allosteric SHP2 inhibitor, with IC₅₀s of 0.690, 1.241, 0.416, 1.968, 2.896 μM for SHP2, SHP2^D61Y, SHP2E69K, SHP2^A72V, SHP2^E76K. SHP099 inhibits cancer cell growth, such as MV4-11 and TF-1 cell (IC₅₀: 0.32 and 1.73 μM). SHP099 inhibits RAS-ERK signaling and inhibits tumor growth.

Oleanolic acid (Caryophyllin) is a natural compound from plants with anti-tumor activities.

LB-100 is a protein phosphatase 2A (PP2A) inhibitor, with IC₅₀ of 0.85 μM and 3.87 μM in BxPc-3 and Panc-1 cells.

TPI-1, also known as Tyrosine Phosphatase Inhibitor 1, is a SHP-1 inhibitor; inhibits recombinant SHP-1 with an IC₅₀ of 40 nM.

Osunprotafib (ABBV-CLS-484) is an orally active and selective active site PTPN1 (IC₅₀: 2.5 nM) and PTPN2(IC₅₀: 1.8 nM) inhibitor. Osunprotafib has 6-8-fold weaker activity on PTPN9 and no detectable activity on SHP-1 or SHP-2. Osunprotafib increases the sensitivity of human cancer cell lines to IFNγ. Osunprotafib generates robust anti-tumor immunity by enhancing JAK-STAT signalling and reducing T cell dysfunction.

Batoprotafib (TNO155) is a potent selective and orally active allosteric inhibitor of wild-type SHP2 (IC₅₀=0.011 µM). Batoprotafib has the potential for the study of RTK-dependent malignancies, especially advanced solid tumors.

Sodium metatungstate (Sodium polyoxotungstate) is a NTPDase inhibitor, with K_i values of 2.58 μM, 3.26 μM, and 28.8 μM for NTPDase 1 (CD39), NTPDase 3 and NTPDase 2 respectively. Sodium metatungstate has anti-inflammatory and anti-cancer effect. Sodium metatungstate inhibits ATP breakdown but also blocks central synaptic transmission.

Idoxuridine (5-Iodo-2′-deoxyuridine, 5-IUdR, IdUrd) is an iodinated thymidine analogue that competitively inhibits phosphorylases. Idoxuridine can inhibit viral activity, particularly viral eye infections, including herpes simplex keratitis, by inhibiting DNA polymerase and affecting viral replication. Idoxuridine against feline herpesvirus has the IC₅₀ value of 4.3 μM. Idoxuridine shows anti-orthopoxvirus activity.

BCI ((E)-BCI) is a DUSP6 (dual specificity phosphatase 6) inhibitor. BCI shows anti-inflammatory activity and decreases reactive oxygen species (ROS) production. BCI can be used in inflammatory disease research.