CYP3A4 Inhibitor

NNC 55-0396 (NNC 55-0396 dihydrochloride) is a blood-brain-barrier-permeable T-type Ca²⁺ channel inhibitor and pan-P450 inhibitor. NNC 55-0396 selectively inhibits T-type Ca²⁺ channels, suppresses HIF-1α expression and stability and inhibits Kv currents. NNC 55-0396 reduces brain infarct and attenuates neurological dysfunction. NNC 55-0396 inhibits the activity of multiple P450 enzymes. NNC 55-0396 (free base) can be used for the research of brain injury, hypertension, and glioblastoma.

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.

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.

NN1177 (NNC9204-1177) TFA is a long-acting GLP-1/glucagon receptor co-agonist. NN1177 TFA can induce a dose-dependent body weight loss in diet-induced obese (DIO) mice.

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

Sorafenib N-oxide is an active metabolite of sorafenib (HY-10201). Sorafenib N-oxide is a linear-mixed inhibitor of microsomal CYP3A4, with a K_i of 15 μM.

Simmitecan hydrochloride is a potent topoisomerase I (TOP1) inhibitor, which is a 9-substituted lipophilic camptothecin (Camptothecin (HY-16560)) derivative. Simmitecan hydrochloride blocks DNA replication and transcription, thereby inducing tumor cell apoptosis by inhibiting the activity of TOP1. Simmitecan hydrochloride can be used for research on cancers such as liver cancer.

P-gp inhibitor 23 (compound 14F) is a potent inhibitor of P-gp and CYP3A4, with the EC₅₀ and IC₅₀ of 28 nM and 223 nM, respectively.

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.

(Rac)-Tamsulosin (YM12617 (free base); (Rac)-LY253351 (free base)) is an isomer of Tamsulosin (HY-B0661). (Rac)-Tamsulosin is a sulfonamide phenethylamine derivative and a competitive antagonist of selective post-synaptic α₁-adrenoceptors. (Rac)-Tamsulosin inhibits CYP3A4 activity in a non-competitive, enantiomer-specific manner, with an IC₅₀ and K_i of 6.75 μM. (Rac)-Tamsulosin produces dose-dependent hypotension, preferentially antagonizing α₁-adrenoceptor-mediated pressor responses, and inhibits α₂-adrenoceptor-mediated pressor responses at high doses. (Rac)-Tamsulosin can be used in research related to various diseases such as metabolism.

BMS-344577 (Compound 22) is a potent and orally active factor Xa inhibitor (IC₅₀ = 4 nM, EC2xPT = 7 μM). BMS-344577 shows potent CYP3A4 inhibition activity (IC₅₀ = 0.3 μM). BMS-344577 can be used for the research of cardiovascular disease.

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.

Tamsolusin hydrochloride (YM12617 hydrochloride; LY253351 hydrochloride) is an isomer of Tamsulosin (HY-B0661). Tamsolusin hydrochloride is a sulfonamide phenethylamine derivative and a competitive antagonist of selective post-synaptic α₁-adrenoceptors. Tamsolusin hydrochloride inhibits CYP3A4 activity in a non-competitive, enantiomer-specific manner, with an IC₅₀ and K_i of 6.75 μM. Tamsolusin hydrochloride produces dose-dependent hypotension, preferentially antagonizing α₁-adrenoceptor-mediated pressor responses, and inhibits α₂-adrenoceptor-mediated pressor responses at high doses. Tamsolusin hydrochloride can be used in research related to various diseases such as metabolism.

NNC 55-0396 free base is a blood-brain-barrier-permeable T-type Ca²⁺ channel inhibitor and pan-P450 inhibitor. NNC 55-0396 free base selectively inhibits T-type Ca²⁺ channels, suppresses HIF-1α expression and stability and inhibits Kv currents. NNC 55-0396 free base reduces brain infarct and attenuates neurological dysfunction. NNC 55-0396 free base inhibits the activity of multiple P450 enzymes. NNC 55-0396 (free base) can be used for the research of brain injury, hypertension, and glioblastoma.

Simmitecan is a potent topoisomerase I (TOP1) inhibitor, which is a 9-substituted lipophilic camptothecin (Camptothecin (HY-16560)) derivative. Simmitecan blocks DNA replication and transcription, thereby inducing tumor cell apoptosis by inhibiting the activity of TOP1. Simmitecan can be used in the research of cancers such as liver cancer.