Cytochrome P450 Inhibitor

Itraconazole (R51211) is a triazole antifungal agent and a potent and orally active Hedgehog (Hh) signaling pathway antagonist with an IC₅₀ of ~800 nM. Itraconazole potently inhibits lanosterol 14α-demethylase (cytochrome P450 enzyme), thereby inhibits the oxidative conversion of lanosterol to ergosterol. Itraconazole has anticancer and antiangiogenic effects. Itraconazole is a oxysterol-binding protein (OSBP) inhibitor.

Naringin is a major flavanone glycoside obtained from tomatoes, grapefruits, and many other citrus fruits. Naringin exhibits biological properties such as antioxidant, anti-inflammatory, and antiapoptotic activities. Naringin also inhibits proliferation and invasion and induces apoptosis in human osteosarcoma cells by inhibiting zinc finger E-box binding homeobox 1 (Zeb1).

Hypericin is a naturally occurring substance found in Hyperlcurn perforatum L. Hypericin is an inhibitor of PKC (protein kinase C), MAO (monoaminoxidase), dopamine-beta-hydroxylase, reverse transcriptase, telomerase and CYP (cytochrome P450). Hypericin shows antitumor, antiviral, antidepressive activities, and can induce apoptosis.

Metyrapone (Su-4885) is a potent and orally active 11β-hydroxylase inhibitor and an autophagy activator, also inhibits the production of aldosterone. Metyrapone inhibits synthesis of endogenous adrenal corticosteroid, decreases glucocorticoid levels, and also affects behavior and emotion. In addition, Metyrapone increases the efficiency of autophagic process via downregulation of mTOR pathway, and interacts with Pseudomonas putida cytochrome P-450. Metyrapone can be used for researching Cushing's syndrome and depression.

Methoxsalen (8-Methoxypsoralen) is a furanocoumarin compound used in psoralen, used in studies of psoriasis, eczema, vitiligo and some sun-exposed cutaneous lymphomas, and is a P450 inhibitor.

Bergapten is a natural anti-inflammatory and anti-tumor agent. Bergapten is inhibitory towards mouse and human CYP isoforms.

17-ODYA is a CYP450 ω-hydroxylase inhibitor. 17-ODYA is also a potent inhibitor (IC₅₀<100 nM) of the formation of 20-hydroxyeicosatetraenoic acid (20-HETE), epoxyeicosatrienoic acids and dihydroxyeicosatrienoic acids by rat renal cortical microsomes incubated with arachidonic acid. 17-ODYA completely attenuates the isoproterenol (ISO)-induced apoptosis, and necrosis in cultured cardiomyocytes. 17-ODYA is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

Furafylline is a potent and selective inhibitor of human cytochrome P450IA2 with an IC₅₀ of 0.07 μM.

Mitiperstat (AZD4831) is an effective oral inhibitor of myeloperoxidase (MPO). Mitiperstat inhibits MPO and thyroid peroxidase (TPO) with IC₅₀s of 1.5 nM and 0.69 μM. Mitiperstat exhibits a weak inhibitory activity against CYP3A4 with an IC₅₀ of 6 μM. Mitiperstat can reduce inflammation and improve microvascular function, and it can be used in studies related to heart failure, preserved or mildly reduced ejection fraction, non-alcoholic fatty liver disease, and chronic obstructive pulmonary disease.

ADDA 5 hydrochloride is a partial non-competitive inhibitor of cytochrome c oxidase (CcO), with IC₅₀s of 18.93 μM and 31.82 μM for purified CcO from human glioma and bovine heart, respectively.

Dafadine-A is a selective inhibitor of DAF-9 cytochrome P450 in the nematode Caenorhabditis elegans. Dafadine-A inhibits the mammalian ortholog of DAF-9 (CYP27A1). Dafadine-A does not inhibits DAF-12 and sterol- and oxysterol-metabolizing P450s.

Opevesostat (MK-5684; ODM-208) is an orally active and selective CYP11A1 inhibitor. Opevesostat has the potential for the research of metastatic castration-resistant prostate cancer (mCRPC).

Soticlestat (TAK-935; OV935) is a first-in-class, potent, selective, and orally active cholesterol 24-hydroxylase (CH24H) inhibitor. Soticlestat has the potential for epilepsy syndromes research.

Proadifen (SKF-525A) hydrochloride is a non-competitive Cytochrome P450 inhibitor with an IC₅₀ value of 19 μM. Proadifen hydrochloride reduces monoamine oxidase A (MAO-A) activity and reverses the antidepressantlike behavioral effect of Imipramine (HY-B1490A) and Desipramine (HY-B1272A) in rats. Proadifen hydrochloride also reduces N, N-dimethyltryptamine (DMT) metabolism in liver microsomes and inhibits N-demethylationand Acridone (HY-W007771) formation. Proadifen hydrochloride augments Lipopolysaccharide (LPS) (HY-D1056)-induced fever and exacerbates Prostaglandin E2 (PGE2) (HY-101952) levels in the rat. Proadifen hydrochloride is promising for research of metabolism-related deseases, ovarian carcinoma, inflammation and dopamine neurons-related deseases.

Karanjin is an orally active furanoflavonoid which can be isolated from several Leguminosae. Karanjin exhibits evident anti-diabetic, anti-cancer, anti-inflammatory, antioxidant, anticolitis, anti-ulcer, anti-Alzheimer properties and multiple insect repellent/insecticidal, acaricide properties, suggesting the potential of Karanjin to be applied to relevant research.

Econazole ((±)-Econazol) is an orally active imidazole antifungal agent, as well as a cytochrome P-450 inhibitor and a blocker of calcium and manganese ion uptake. Econazole is active against a variety of fungi and some Gram-positive bacteria, but has no significant activity against Gram-negative bacteria. Econazole can inhibit the synthesis of prostaglandins and can also induce liver damage.

Feruloylputrescine is an oral active phenolamide found in citrus plants and formed through the decarboxylation of L-Arginine. Feruloylputrescine inhibits monooxygenase (cntA) and reductase (cntB) and trimethylamine production. Feruloylputrescine can be used for cardiovascular diseases research.

Antimycin A2 is a selective inhibitor of the cytochrome b-c1 complex in the mitochondrial electron transport chain. Antimycin A2 disrupts mitochondrial membrane potential and produces reactive oxygen species (ROS) by inhibiting electron transfer between cytochrome b and c. Antimycin A2 has bactericidal and piscicidal activity, as well as tumor cell growth inhibitory effects, and can induce S-phase cell cycle arrest and apoptosis in HeLa cells. Antimycin A2 is suitable for research of cervical cancer and fisheries management. Antimycin A2 can be naturally isolated from the fermentation products of Streptomyces sp. strains.

Lorundrostat (MT-4129) is an orally active aldosterone synthase inhibitor. Lorundrostat can be used in studies of high blood pressure.

Quercetin 3-gentiobioside is a flavonoid found in Artemisia iwayomogi. Quercetin 3-gentiobioside inhibits aromatase with an K_i of 46.77 nM. Quercetin 3-gentiobioside inhibits aldose reductase (AR) and the formation of advanced glycation end products (AGEs), with IC₅₀ values of 10.60 μM and 109.46 μM, respectively. Quercetin 3-gentiobioside inhibits proliferation of cancer cells and fibroblast-like synoviocytes. Quercetin 3-gentiobioside can be used for the research of cancer, such as lung carcinoma.