Epoxide Hydrolase Inhibitor

TPPU is a soluble epoxide hydrolase (sEH) inhibitor with IC₅₀ values of 37 and 3.7 nM for monkey and human sEH, respectively.

GSK2256294A (GSK 2256294) is a selective and orally active inhibitor of soluble epoxide hydrolase (sEH). GSK2256294A inhibits recombinant human sEH, rat sEH orthologs and murine sEH orthologs with IC₅₀s of 27, 61 and 189 pM, respectively. GSK2256294A can be used for the research of chronic obstructive pulmonary disease (COPD) and cardiovascular disease.

EC5026 (BPN-19186) is a first-in-class, non-opioid and orally active soluble Epoxide Hydrolase (sEH) inhibitor. EC5026 shows efficacy for inflammatory and neuropathic pain.

AUDA (compound 43) is a potent soluble epoxide hydrolase (sEH) inhibitor with IC₅₀s of 18 and 69 nM for the mouse and human sEH, respectively. AUDA has anti-inflammatory activity.

trans-AUCB (t-AUCB) is a potent, orally active and selective soluble epoxide hydrolase (sEH) inhibitor with IC₅₀s of 1.3 nM, 8 nM, 8 nM for hsEH, mouse sEH and rat sEH, respectively. trans-AUCB has anti-glioma activity.

sEH-IN-24 is an orally active soluble epoxide hydrolase (sEH) inhibitor with an IC₅₀ of 1.9 nM. sEH-IN-24 inhibits the pro-inflammatory cytokines TNF-α and IL-6. sEH-IN-24 exhibits anti-inflammatory effects and exerts analgesic activity in vivo. sEH-IN-24 prevents pancreatic edema, inflammation and parenchymal atrophy. sEH-IN-24 can be used for the research of acute pancreatitis.

SH-11037 is a potent inhibitor of soluble epoxide hydrolase (sEH) and docks to the substrate binding cleft in the sEH hydrolase domain. SH-11037 dose-dependently suppresses angiogenesis in the choroidal sprouting assay ex vivo and inhibited ocular developmental angiogenesis in zebrafish larvae. SH-11037 reduces choroidal neovascularisation lesion volume in the laser-induced CNV mouse model. SH-11037 synergises with anti-VEGF treatments in vitro and in vivo. SH-11037 induces G2/M phase blockade and retains retinal endothelial cell viability at active concentrations without overt toxicity. SH-11037 can be used for the research of retinal neovascularization and ocular neovascularization.

sEH-IN-23 is a soluble epoxide hydrolase inhibitor with a IC₅₀ of 0.8 nM against human sEH and 0.7 nM against murine sEH. sEH-IN-23 inhibits inflammatory factor production mediated by NF-κB activation, reactive oxygen species (ROS) generation, and the release of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α. sEH-IN-23 exhibits anti-inflammatory activity in acute lung injury models. sEH-IN-23 can be used for the research of acute lung injury.

UC-1728 is a potent rabbit soluble epoxide hydrolase (sEH) inhibitor, with an IC₅₀ of 2 nM on rabbit liver.

AR9281 (APAU) is a potent, selective and orally active soluble epoxide hydrolase (s-EH) inhibitor. AR-9281 can inhibits human sEH (HsEH) and murine sEH (MsEH) with IC₅₀ values of 13.8 nM and 1.7 nM, respectively. AR9281 can be used for the research of inflammation, hypertension and type 2 diabetes.

Alisol B is a triterpene with diverse biological activities. Alisol B binds human soluble epoxide hydrolase (sEH) with a K_i of 5.97 μM and reduces sEH activity. Alisol B inhibits RANKL-induced JNK phosphorylation, NFATc1 and c-Fos expression, osteoclast formation, mature osteoclast pit-forming and actin ring activity, and SERCA pump activity. Alisol B induces calcium mobilization, CaMKK-AMPK-mTOR pathway activation, autophagic flux, autophagosome formation, G₁ phase cell cycle arrest, endoplasmic reticulum stress, unfolded protein responses, and cancer cell apoptosis. Alisol B can be used for the research of hypercalcemia, osteoporosis, rheumatoid arthritis, periodontitis, acute kidney injury, and breast cancer.

mEH-IN-1 (Compound 62) is a potent microsomal epoxide hydrolase (mEH) inhibitor with the IC₅₀ of 2.2 nM. The mEH is a mammalian α/β-fold hydrolase enzyme, expressed in almost all tissues, hydrolyzes a wide range of epoxide containing molecules. The mEH is mainly localized in the endoplasmic reticulum (ER) of eukaryotic cells. mEH-IN-1 can be used for the research of preeclampsia, hypercholanemia and cancer.

LYPLAL1-IN-1 (compound 11) is a selective, covalent, and irreversible inhibitor of the lysophospholipase-like enzyme LYPLAL1 (IC₅₀ = 6 nM). LYPLAL1-IN-1 shows selectivity against other serine hydrolases such as carboxylesterase CES1 (IC₅₀ > 50 μM for CES1). LYPLAL1-IN-1 inhibits the depalmitoylation function of LYPLAL1, blocking its depalmitoylation modification of cyclic GMP-AMP synthase (cGAS), thereby promoting cGAS dimerization and activation, and initiating the cGAS-STING pathway-mediated innate immune response. LYPLAL1-IN-1 can enhance DNA-induced type I interferon production, upregulate PD-L1 expression in tumor cells, and promote the accumulation of tumor-infiltrating CD8⁺ T cells, with the core function of strengthening the anti-tumor immune response. LYPLAL1-IN-1 is primarily used in tumor immunology research, especially in combination with PD-1/PD-L1 inhibitors.

SWE101 (compound 22 b) is a potent soluble epoxide hydrolase (sEH)-P inhibitor with IC₅₀s of 4 μM and 2.8 μM for human and rat sEH-P, respectively. SWE101 does not inhibit neither hydrolase nor phosphatase activity of the mouse sEH.

Valpromide is an amide derivative of Valproic acid (HY-10585) and an orally active epoxide hydrolase inhibitor that can cross the blood-brain barrier. Valpromide has antiepileptic, anticonvulsant, and antipsychotic effects. Valpromide also exhibits antiviral activity and can inhibit the reactivation of the EBV lytic cycle.

CUDA is a potent inhibitor of soluble epoxide hydrolase (sEH), with IC₅₀s of 11.1 nM and 112 nM for mouse sEH and human sEH, respectively. CUDA selectively increases peroxisome proliferator-activated receptor (PPAR) alpha activity. CUDA may be valuable for the research of cardiovascular disease.

BI-1935, a chemical probe, is a potent soluble epoxide hydrolase (sEH) inhibitor. BI-1935 can be used for the research of cardiovascular disease.

VU534 is a NAPE-PLD activator, with an EC₅₀ of 0.30 μM. VU534 is dual inhibitors of FAAH and sEH (IC₅₀ of 1.2 μM). VU534 increases efferocytosis in a NAPE-PLD dependent manner. VU534 has the potential for cardiometabolic diseases study ^[1] .

Diflapolin is a highly active dual 5-lipoxygenase-activating protein (FLAP)/soluble epoxide hydrolase (sEH) inhibitor with marked anti-inflammatory efficacy and high target selectivity. Diflapolin inhibits 5-LOX product formation in intact human monocytes and neutrophils with IC₅₀s?of? 30 and 170?nM, respectively, and suppressed the activity of isolated sEH (IC₅₀=20?nM).

Ibuprofenamide (Compound 136) is a potent microsomal epoxide hydrolase (mEH) inhibitor with an IC₅₀ value of 96 μM. Ibuprofenamide is promising for research of preeclampsia, hypercholanemia and cancer.