Cytochrome P450 Inhibitor

Liarozole (R75251; R85246) is an imidazole derivative and orally active retinoic acid (RA) metabolism-blocking agent (RAMBA). Liarozole inhibits the cytochrome P450 (CYP26)-dependent 4-hydroxylation of retinoic acid (IC₅₀=7 μM), resulting in increased tissue levels of retinoic acid. Liarozole shows antitumoral properties.

Benoxaprofen (LRCL 3794) is a nonsteroidal anti-inflammatory agent that blocks the biosynthesis of inflammatory mediators such as leukotrienes and prostaglandins by inhibiting 5-LOX, PGH2 synthase and cytochrome P-450. Benoxaprofen exhibits significant toxicity: it not only alters cellular redox status, uncouples oxidative phosphorylation and disrupts calcium ion homeostasis, but also causes liver injury through the formation of covalent adducts between its active metabolites and hepatic proteins. Benoxaprofen shows strong phototoxicity under ultraviolet irradiation, and induces erythrocyte lysis, mast cell degranulation and histamine release. Benoxaprofen is widely used in studies of urticaria and related phototoxic mechanisms.

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.

Quinidine sulfate is an antiarrhythmic agent. Quinidine sulfate is a potent, orally active, selective cytochrome P450db inhibitor. Quinidine sulfate is also a K⁺ channel blocker with an IC₅₀ of 19.9 μM. Quinidine sulfate can be used for malaria research.

21-Hydroxypregnenolone is a CYP17 inhibitor. 21-Hydroxypregnenolone competitively inhibits CYP17-mediated 17α-hydroxylation activity of progesterone, with a Ki value of 36.4 μM.

Azamulin is an irreversible, highly selective inhibitior of human CYP3Aa. Azamulin has CYP3A inhibition activity with IC₅₀ values range from 0.03-0.24 μM. Azamulin can be used for the research of metabolism and antiinfection.

20-HETE inhibitor-2 is an orally active 20-HETE inhibitor. 20-HETE inhibitor-2 can inhibit the activities of CYP4F2 and CYP4A11, thereby suppressing the production of 20-HETE. 20-HETE inhibitor-2 has the effect of improving blood glucose and can be used for the research of various diseases related to 20-HETE such as obesity.

BMS-986202 is a potent, selective and orally active Tyk2 inhibitor that binds to Tyk2 JH2 with an IC₅₀ value of 0.19 nM and a K_i of 0.02 nM. BMS-986202 is remarkably selective over other kinases including Jak family members. BMS-986202 is also a weak inhibitor of CYP2C19 with an IC₅₀ value of 14 μM. BMS-986202 can be used for IL-23-driven acanthosis, anti-CD40-induced colitis, and spontaneous lupus research. BMS-986202 is a de novo deuterium.

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.

Octinoxate (Octyl methoxycinnamate) is a thyroid hormone receptor agonist, reducing the levels of triiodothyronine (T3) and thyroxine (T4) and transcription levels of genes related to type II deiodinase (deio2) in Japanese Medaka. Octinoxate is commonly used as a safe ultraviolet (UV) filter used in the aquatic environment. Octinoxate inhibits CYP1A1 and CYP1B1 to regulate hyaluronan (HA) (HY-B0633A) metabolism in a PI3K pathway-dependent manner in human keratinocytes. Octinoxate also exhibits an anti-estrogenic and anti-androgenic effect in vitro and in vivo.

Aminoglutethimide (DL-Aminoglutethimide) is an orally active anticonvulsant with various endocrine-related side effects. Aminoglutethimide blocks multiple steroid hormone synthesis pathways by inhibiting several cytochrome P-450-dependent hydroxylases, such as aromatase, cholesterol side-chain cleavage enzyme, 11-hydroxylase, and 18-hydroxylase, with IC₅₀ values of 0.3, 3.5, 120, and 20 μM, respectively. Aminoglutethimide reduces cortisol levels. Aminoglutethimide can be used in research on Cushing's syndrome, breast cancer, and other conditions.

Columbamine (Columbamin; Dehydroisocorypalmine) chloride is an organic heterotetracyclic alkaloid extracted from plants. Columbamine chloride is a metabolite of Berberine (HY-N0716). Columbamine chloride inhibits the cytochrome P450 (CYP) isoform CYP3A4 (IC50 = 30.6 µM). Columbamine chloride induces apoptosis in cancer cells. Columbamine chloride can be used for antioxidant, anti-inflammatory, antitumor, antifungal, antiparasite, hepatoprotective, neuroprotective, hypolipidemic and hypoglycemic study.

Obtusifoliol is a specific CYP51 inhibitor, Obtusifoliol shows the affinity with K_d values of 1.2 μM and 1.4 μM for Trypanosoma brucei (TB) and human CYP51, respectively.

Clitorin is an orally active flavonoid compound that can be isolated from Carica papaya. Clitorin is an inhibitor of EGFR (IC₅₀: 89.58 nM) and aromatase (IC₅₀: 77.41 nM). Clitorin has antioxidant and anti-tumor activities. In the DPPH and ABTS radical scavenging assays, Clitorin has IC₅₀ values of 91.96 ppm and 250.45 ppm, respectively. In addition, Clitorin can regulate lipogenesis and fatty acid oxidation and can be used in the research of non-alcoholic fatty liver disease.

Endoxifen hydrochloride is a key active metabolite of Tamoxifen (TAM) with higher affinity and specificity to estrogen receptor that also inhibits aromatase activity. Endoxifen hydrochloride has the potential for breast cancer study.

Fadrozole (CGS 16949A free base) is a potent, selective and nonsteroidal inhibitor of aromatase with an IC₅₀ of 6.4 nM.

Flavanone is a naturally occurring flavone. Flavanone has inhibitory activity for human estrogen synthetase (aromatase). Flavanone is the inhibitor for ERK/p38/NF-κB signaling pathway. Flavanone exhibits oral activity and antitumor efficacy.

Piperlonguminine is a cytochrome P450 (CYP450) inhibitor. Piperlonguminine also inhibits the growth of epimastigotes and intracellular amastigotes of Trypanosoma cruzi, with IC₅₀ values of 53.8 and 33.9 μM, respectively. Piperlonguminine regulates HMGB1/TLR4-NF-κB/MAPK-related inflammatory responses, endothelial protein C receptor (EPCR) shedding, melanogenesis, glycolipid metabolism, ischemic brain injury and tumor growth. Piperlonguminine can be used in research on hyperlipidemia, sepsis, Chagas disease, ischemic stroke, sarcoma and severe acute pancreatitis-associated lung injury.

Tetrahydropiperine is an orally effective, selective inhibitor of NF-κB and MAPKs, and an activator of the PI3K/Akt/mTOR pathway. Tetrahydropiperine reduces the production of pro-inflammatory cytokines such as TNF-α, IL-6, and nitric oxide (NO) by inhibiting the nuclear translocation of NF-κB and the phosphorylation of MAPKs such as ERK, JNK, and p38. At the same time, Tetrahydropiperine inhibits excessive autophagy by activating the PI3K/Akt/mTOR pathway, protecting neurons from oxidative damage. Tetrahydropiperine has anti-inflammatory, anti-apoptotic, and neuroprotective effects, and is mainly used in the study of inflammatory diseases (such as endotoxemia, arthritis) and neurological diseases such as ischemic stroke.