20-HETE

20-HETE belongs to endogenous metabolites (natural products) and is a protein kinase C (PKC) pathway activator that promotes ACSL4 ubiquitination and degradation through upregulation of FBXO10, possessing regulatory properties on cell proliferation and migration. This compound is used in research related to prostate tumors and cardiac hypertrophy.

20-HETE inhibitor-2 is an effective inhibitor of 20-HETE synthesis. It reduces 20-HETE production by blocking CYP4A/CYP4F, exhibiting antihypertensive and renoprotective effects in cardiovascular research.

20-HETE Inhibitor-1 (Comp 83) serves as an inhibitor of 20-HETE formation [1].

Squalane is a lipid found in some fish oils (especially shark liver oil) and some vegetable oils. It has anticancer and antioxidant properties and is used as a skin moisturizer and emollient.

N-(3-Chloro-4-morpholinophenyl)-N'-hydroxyformimidamide (TS-011) is a selective 20-Hydroxyeicosatetraenoic acid synthesis inhibitor.

CAY10462 (CTK8E8405) is an effective and selective inhibitor of the 20-HETE synthase CYP4A11 with an IC50 of 8.8 nM. CAY10462 exhibits nearly 200 times less potent for 1A, 1C, and 3A CYP450 enzymes.

CYP4A11/CYP4F2-IN-2 is a potent and orally active dual inhibitor of cytochrome P450 (CYP) 4A11 and CYP4F2, with IC50 values of 140 nM and 40 nM, respectively. Extractable from liver and kidney, CYP4A11/CYP4F2-IN-2 has the potential to treat kidney diseases.

CYP4A11/CYP4F2-IN-1 is a cytochrome P450 (CYP) 4A11 and CYP4F2 inhibitor, applicable for research on kidney, cardiovascular, and cerebrovascular diseases.

HET0016 is a potent and selective 20-HETE synthase inhibitor (IC50s: 17.7 nM, 12.1 nM, and 20.6 nM for recombinant CYP4A1-, CYP4A2-, and CYP4A3-catalyzed 20-HETE synthesis) and a selective CYP450 inhibitor, shown to inhibit angiogenesis and tumor growth.

20-HEDE (WIT 002) is an antagonist of 20-hydroxyeicosatetraenoic acid (20-HETE).

15-LOX-IN-2 (Compound 2a) is an orally active inhibitor of COX-2/15-LOX and a partial agonist of PPARγ. It exhibits anti-inflammatory activity by inhibiting levels of 20-HETE, IL-1β, and TNF-α in LPS-treated RAW 264.7 cells. Additionally, it significantly enhances glucose uptake without the presence of insulin and is applicable in metabolic disease research.

20-SOLA is the first water-soluble 20-HETE antagonist with oral bioavailability. It significantly improves blood pressure changes and kidney damage associated with the streptozotocin (STZ) diabetic mouse model. Additionally, 20-SOLA acts as a GPR75 receptor blocker. This compound is useful in research related to cardiovascular pathology.

AAA is an antagonist of G protein-coupled receptor 75 (GPR75).1It increases basal GPR75 protein levels and inhibits 20-HETE-induced reductions in GPR75 protein levels in PC3 cells. AAA (5 and 10 μM) also reduces 20-HETE-induced phosphorylation of EGFR, NF-κB, and Akt in, and cell migration of, PC3 cells.In vivo, AAA (10 mg/kg per day) reduces systolic blood pressure, albuminuria, renal angiotensin II levels, and cardiac hypertrophy in a Cyp1a1-Ren-2 transgenic rat model of malignant hypertension when administered prior to induction or after establishment of hypertension.2 1.Cárdenas, S., Colombero, C., Panelo, L., et al.GPR75 receptor mediates 20-HETE-signaling and metastatic features of androgen-insensitive prostate cancer cellsBiochim. Biophys. Acta Mol. Cell Biol. Lipids1865(2)158573(2020) 2.Sedláková, L., Kikerlová, S., Husková, Z., et al.20-Hydroxyeicosatetraenoic acid antagonist attenuates the development of malignant hypertension and reverses it once established: a study in Cyp1a1-Ren-2 transgenic ratsBiosci. Rep.38(5)BSR20171496(2018)

20-carboxy Arachidonic acid (20-COOH-AA) is the major metabolite of 20-HETE that is produced in renal tubular epithelial, endothelial, and microvascular smooth muscle cell cultures. This ω-oxidation conversion can take place using purified alcohol dehydrogenases three and four or by microsomes containing recombinant human CYP4F3B. Like 20-HETE, 20-COOH-AA inhibits ion transport in the kidneys. It also produces vasorelaxation of porcine coronary microvessels constricted with endothelin. 20-COOH-AA binds to isolated ligand binding domains of peroxisome proliferator-activated receptor α (PPARα) (Kd = 0.87 ± 0.12 μM) and PPARγ (Kd = 1.7 ± 0.5 μM), and is a dual activator of PPARα and PPARγ in a transiently transfected COS-7 cell reporter system.

20-5,14-HEDGE, a 20-HETE analog, protects against lung ischemic reperfusion injury in rats [1].

CYP4A11/CYP4F2-IN-2 (compound 15) serves as an orally administered inhibitor targeting CYP4A11/4F2, exhibiting IC50 values of 120 nM and 220 nM, respectively. This compound effectively suppresses 20-HETE production within the rat kidney and shows promise in mitigating the progression of diabetic nephropathy and autosomal dominant polycystic kidney disease [1].