CYP2C19 Inhibitor

(S)-(+)-N-3-Benzylnirvanol ((+)-N-3-Benzylnirvanol) is a selective and competitive cytochrome P450 (CYP) isoform CYP2C19 inhibitor with a K_i of 250 nM. (S)-(+)-N-3-Benzylnirvanol has low activity against CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2D6, CYP2E1, and CYP3A4.

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.

HBV-IN-57 is an orally active HBV inhibitor with pan-genotypic efficacy against HBV genotypes B/C. HBV-IN-57 inhibits HBV DNA replication and HBV capsid assembly. HBV-IN-57 can be used for the research of chronic hepatitis B.

FGFRs-IN-1 (Compound A16) is the orally active inhibitor for FGFR, that inhibits FGFR1/2/3/4 with IC₅₀s of 2.3, 7, 11, and 163 nM, respectively. FGFRs-IN-1 also inhibits VEGFR1/2/3, Abl, and Flt3 with IC₅₀s of 61, 176, 112, 26, and 353 nM, respectively. FGFRs-IN-1 exhibits weak inhibitory efficacy against CYP enzymes. FGFRs-IN-1 reduces the expression of α-SMA and collagen I, and inhibits epithelial-mesenchymal transition (EMT) in TGF-β1 stimulated A549 cell. FGFRs-IN-1 exhibits anti-inflammatory activity in Bleomycin (HY-17565)-induced mouse pulmonary fibrosis model and CCl₄ (HY-Y0298)-induced mouse liver fibrosis model.

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.

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.