CYP2C9 Inhibitor

Oteseconazole (VT-1161) is a potent and orally active anti-fungal agent. Oteseconazole potently binds to and inhibits Candida albicans cytochrome P45051 (CYP51) activity (K_d ≤39 nM), shows no obvious effect on human CYP51. Oteseconazole also can be used for the research of dermatophytes.

Dihydrokavain (7,8-Dihydrokawain) is a natural kavalactone compound. Dihydrokavain inhibits COX-1, COX-2, CYP2C9 (IC₅₀ = 130.95 μM), CYP2C19 (IC₅₀ = 10.05 μM) and CYP3A4 (IC₅₀ = 78.59 μM). Dihydrokavain reduces TNFα secretion. Dihydrokavain shows analgesic and anxiolytic effects.

Nivasorexant (ACT-539313) is an orally active, blood-brain barrier penetrant, selective orexin OX1R inhibitor. Nivasorexant specifically blocks central OX1Rs without affecting OX2Rs, and exhibits competitive inhibitory activity against CYP2C8, CYP2C9, CYP2C19 and CYP3A4 (IC₅₀ values are 25 μM, 8.6 μM, 1.6 μM, 19 μM/44 μM, respectively). Nivasorexant significantly reduces binge-like eating behavior of highly palatable food in rat models and has long-acting properties. Nivasorexant shows no relevant off-target activity against over 130 selected proteins, exhibits favorable safety profiles, and can be used for studies related to binge eating disorder.

BMS-223131 (Compound 1) is a potent maxi-K potassium channel opener. BMS-223131 has a strong inhibitory effect on the CYP2C9 enzyme (IC₅₀ = 1.7 μM) and also shows varying degrees of inhibition on other common CYP enzymes such as CYP1A2, CYP2C19, CYP2D6, and CYP3A4. BMS-223131 can enhance the outward current mediated by maxi-K, by promoting K⁺ efflux to hyperpolarize the cell membrane and reducing Ca²⁺ influx. BMS-223131 can be used for the research of neurological disease, such as stroke.

Cloperidone hydrochloride acts as an inhibitor and substrate of CYP2C9, with an IC₅₀ of 17.7 μM. Cloperidone hydrochloride exhibits enhanced cytotoxicity in cells expressing CYP2C9. It can be used in the research of sedative/hypnotic-related diseases.

Sulfamethylphenazole (Sulfapyrazole; Vesulong) is a long-acting sulfonamide antibacterial agent. Sulfamethylphenazole maintains effective chemotherapeutic blood concentrations through the slow release of free sulfonamide from a protein-binding reservoir and can be used in combination with antibiotics such as Terramycin for bovine hemorrhagic septicemia. Sulfamethylphenazole exhibits moderate antimycobacterial activity against Mycobacterium tuberculosis H37Rv (MIC = 15.38 μg/mL) and inhibitory activity against CYP 2C9. Sulfamethylphenazole can be used in studies related to tuberculosis and hemorrhagic septicemia.

FGFR2/3-IN-3 is a dual-target FGFR2/3 inhibitor with IC₅₀s of 2.7 nM (TEL-FGFR2) and 3.9 nM (TEL-FGFR3), respectively. FGFR2/3-IN-3 has effective activity against both wild-type and mutant FGFR3. FGFR2/3-IN-3 has low CYP3A4 inhibitory effect and hERG toxicity. FGFR2/3-IN-3 improves the imbalance between chondrocyte proliferation and differentiation and promotes bone growth by inhibiting the signaling pathway mediated by mutant FGFR3. FGFR2/3-IN-3 shows a growth-promoting effect in a dwarfism mouse model and has the potential to study bone development disorder-related diseases such as achondroplasia (ACH).

MK-5596 is an efficient, selective and orally active CB1R (IC₅₀ = 1.0 nM, EC₅₀ = 5.8 nM) inverse agonist. MK-5596 has weak hERG inhibitory activity. MK-5596 has strong weight loss and appetite suppression effects. MK-5596 has a certain inhibitory effect on CYP enzymes (CYP3A4: IC₅₀ = 3.3 μM, CYP2C8: IC₅₀ = 11 μM, CYP2C9: IC₅₀ = 18 μM, CYP2D6: IC₅₀ = 6 μM). MK-5596 can be used for research on conditions such as obesity.

Sulfamethylphenazole potassium (Sulfapyrazole potassium; Vesulong potassium) is a long-acting sulfonamide antibacterial agent. Sulfamethylphenazole potassium maintains effective chemotherapeutic blood concentrations through the slow release of free sulfonamide from a protein-binding reservoir and can be used in combination with antibiotics such as Terramycin for bovine hemorrhagic septicemia. Sulfamethylphenazole potassium exhibits moderate antimycobacterial activity against Mycobacterium tuberculosis H37Rv (MIC = 15.38 μg/mL) and inhibitory activity against CYP 2C9. Sulfamethylphenazole potassium can be used in studies related to tuberculosis and hemorrhagic septicemia.

10-Hydroxywarfarin, a metabolite of (R)-(+)-Warfarin (HY-W015998 ), is a CYP2C9 and vitamin K epoxide reductase complex 1 (VKOR) inhibitor with IC₅₀s of 1.6 µM and 80 ng/mL, respectively.

NNRT-IN-10 is a potent, selective and orally active non-nucleoside HIV-1 reverse transcriptase (NNRTI) inhibitor with with an EC₅₀ values ranging from 1.16 to 18.3 nM for HIV and its mutant strains. NNRT-IN-10 exhibits good pharmacokinetic properties and favorable safety profiles. NNRT-IN-10 can be used for the study of AIDS, caused by HIV-1.

8-Hydroxywarfarin (8-OH Warfarin) is a CYP2C9 inhibitor. 8-Hydroxywarfarin inactivates the anticoagulant activity of Warfarin (HY-B0687) via 8-hydroxylation. 8-Hydroxywarfarin serves as a glucuronidation substrate for UGT1A1, UGT1A8, UGT1A9, as well as wild-type/mutant UGT1A10. This reaction enhances its polarity, solubility and excretion efficiency, and the process is independent of phenylalanine⁹⁰ of UGT1A10. 8-Hydroxywarfarin can be used in studies related to thromboembolic diseases.

Sulfamethylphenazole sodium (Sulfapyrazole sodium; Vesulong sodium) is a long-acting sulfonamide antibacterial agent. Sulfamethylphenazole sodium maintains effective chemotherapeutic blood concentrations through the slow release of free sulfonamide from a protein-binding reservoir and can be used in combination with antibiotics such as Terramycin for bovine hemorrhagic septicemia. Sulfamethylphenazole sodium exhibits moderate antimycobacterial activity against Mycobacterium tuberculosis H37Rv (MIC = 15.38 μg/mL) and inhibitory activity against CYP 2C9. Sulfamethylphenazole sodium can be used in studies related to tuberculosis and hemorrhagic septicemia.

Cloperidone acts as an inhibitor and substrate of CYP2C9, with an IC₅₀ of 17.7 μM. Cloperidone exhibits enhanced cytotoxicity in cells expressing CYP2C9. It can be used in the research of sedative/hypnotic-related diseases.

4-Methoxywarfarin (compound 15) is a racemic inhibitor of cytochrome P450 2C9 (CYP2C9). 4-Methoxywarfarin inhibits CYP2C9-catalyzed S-warfarin 7-hydroxylation with a K_i of 11 μM. 4-Methoxywarfarin is applicable to studies related to CYP2C9 inhibition, warfarin metabolism, and the structure-activity relationship of CYP2C9 inhibitors.