Cytochrome P450 Inhibitor

Troleandomycin (Triacetyloleandomycin), a macrolide acrolide antibiotic, is a selective CYP3A inhibitor. Troleandomycin is an oral corticosteroid for asthma study.

Isavuconazole (BAL-4815) is a triazole proagent with antifungal activity against yeasts, molds, and dimorphic fungi. Isavuconazole inhibits ergosterol biosynthesis and results in the disruption of fungal membrane structure and function. Isavuconazole is a moderate inhibitor of CYP3A4.

Nefazodone is an orally active phenylpiperazine antidepressant. Nefazodone can potently and selectively block postsynaptic 5-HT_2A receptors, and moderately inhibit 5-HT and noradrenaline reuptake. Nefazodone can also relieve the adverse effects of stress on the the immune system of mice. Nefazodone has a high affinity for CYP3A4 isoenzyme, which indicates that it has certain risk of agent-agent interaction.

Clobetasol propionate is a potent and selective CYP3A5 inhibitor with an IC₅₀ of 0.206 μM. Clobetasol propionate has no inhibiting on CYP3A4 or other major CYPs. Clobetasol propionate is a corticosteroid and has the potential for psoriasis and other dermatoses research.

Gemfibrozil is an activator of PPAR-α, used as a lipid-lowering agent; Gemfibrozil is also a nonselective inhibitor of several P450 isoforms, with K_i values for CYP2C9, 2C19, 2C8, and 1A2 of 5.8, 24, 69, and 82 μM, respectively.

TMS ((E)-2,3',4,5'-tetramethoxystilbene) is a selective and competitive CYP1B1 inhibitor with an IC₅₀ of 6 nM and a K_i value of 3 nM. TMS shows a lesser extent inhibitory effect on CYP1A1 (IC₅₀=300 nM) and CYP1A2 (IC₅₀=3.1 μM). TMS is a methylated derivative of resveratrol and has anti-cancer activity.

Atazanavir (BMS-232632) is a highly selective and orally active HIV-1 protease inhibitor . Atazanavir is a substrate and inhibitor of CYP3A4, and an inhibitor of P-glycoprotein (P-gp). Atazanavir is also a SARS-CoV 3CL^pro inhibitor with an IC₅₀ of 3.49 μM. Atazanavir inhibits cardiac fibrosis, hyperlipidemia and induces malignant glioma death.

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.

Clopidogrel hydrogen sulfate is an antiplatelet agent to prevent blood clots. Clopidogrel hydrogen sulfate inhibits CYP2B6 and CYP2C19 with IC₅₀s of 18.2 nM and 524 nM, respectively. Clopidogrel hydrogen sulfate is a potent antithrombotic agent that inhibits ADP-induced platelet aggregation．Clopidogrel hydrogen sulfate also is an orally active P2Y(12) inhibitor.

Bergamottin is a potent and competitive CYP1A1 inhibitor with a K_i of 10.703 nM.

Limonin inhibits HIV-1 with an EC₅₀ of 60.0 μM. Limonin induces human colon adenocarcinoma cells apoptosis with an IC₅₀ of 54.74 μM. Limonin has antiviral and antitumor activities.

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.

Tetrahydrocurcumin is a Curcuminoid found in turmeric (Curcuma longa) that is produced by the reduction of Curcumin. Tetrahydrocurcumin inhibit CYP2C9 and CYP3A4.

Acetylshikonin is an oral active anti-cancer, anti-inflammatory, antioxidant, anti-fertility, antibacterial, and neuroprotective agent. Acetylshikonin is a inhibitor of acetylcholinase (AChE) (IC₅₀=34.6 μM) and nonselective cytochrome P450. Acetylshikonin can induce Apoptosis and Autophagy in cancer cells. Acetylshikonin regulates blood glucose, liver fat metabolism, and renal fibrosis, and is used in the study of diabetes, diabetic nephropathy (DN), obesity, and nonalcoholic fatty liver disease (NAFLD).

Benzyl alcohol is an aromatic alcohol, a colorless liquid with a mild aromatic odor. Benzyl alcohol is an inhibitor of P450 enzyme. Benzyl alcohol mediated Toll-Like Receptor 4 to reduce the inflammatory response of liver injury in mice.

Ticlopidine (PCR 5332), an antithrombotic proagent, acts as an allosteric, noncompetitive inhibitor of CD39 with the IC₅₀ of 81.7 μM. Ticlopidine blocks several NTPDase isoenzymes with IC₅₀s of 170 μM and 149 μM for NTPDase2 and NTPDase3, respectively. Ticlopidine is an inhibitor of CYP2C19 human liver cytochrome. Ticlopidine inhibits CYP2C9 and CYP3A4 with IC₅₀s of 26.0 and 32.3 μM, respectively.

Ginsenoside Rd inhibits TNFα-induced NF-κB transcriptional activity with an IC₅₀ of 12.05±0.82 μM in HepG2 cells. Ginsenoside Rd inhibits expression of COX-2 and iNOS mRNA. Ginsenoside Rd also inhibits Ca²⁺ influx. Ginsenoside Rd inhibits CYP2D6, CYP1A2, CYP3A4, and CYP2C9, with IC₅₀s of 58.0±4.5 μM, 78.4±5.3 μM, 81.7±2.6 μM, and 85.1±9.1 μM, respectively.

Alpha-Naphthoflavone is an orally active flavonoid that is a potent, competitive inhibitor of aromatase with the IC₅₀ and K_i values are 0.5 and 0.2 μM. Alpha-Naphthoflavone can inhibit cell proliferation and induce apoptosis.

7-Ethoxyresorufin (Resorufin ethyl ether) is a fluorometric substrate and competitive inhibitor of cytochrome P450, especially CYP1A1. 7-Ethoxyresorufin also inhibits NO synthase.