CYP3 选择性抑制剂 | 激活剂

Itraconazole (R 51211)

Itraconazole (R 51211) is a relatively potent inhibitor of CYP3A4 with IC50 of 6.1 nM, used as a triazole antifungal agent. Itraconazole is a potent antagonist of the Hedgehog (Hh) signaling pathway. Itraconazole suppresses the growth of glioblastoma through induction of autophagy.

PF-4981517

PF-4981517 (CYP3cide, PF-04981517) is a potent and selective inhibitor of CYP3A4 (P450) with IC50 of 0.03 μM, exhibits >500-fold selectivity over CYP3A5 and CYP3A7.

Cobicistat

Cobicistat is a potent and selective inhibitor of CYP3A with IC50 of 30-285 nM.

Alflutinib (AST2818) mesylate

Alflutinib (AST2818, Furmonertinib) mesylate is a third-generation epidermal growth factor receptor (EGFR) inhibitor that inhibits both EGFR-sensitive mutations and T790M mutations. Alflutinib (AST2818), primarily metabolized by CYP3A4, is also a potent CYP3A4 inducer with EC50 of 0.25 μM.

Tanshinone IIA sulfonate sodium

Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA isolated as the main pharmacologically active natural compound from a traditional Chinese herbal medicine, the dried root of Salvia miltiorrhiza Bunge known as Danshen. Sodium tanshinone IIA sulfonate (STS) is a potent negative allosteric modulator of the human purinergic receptor P2X7. Sodium tanshinone IIA sulfonate (STS) inhibits the activity of CYP3A4 and store-operated Ca2+ entry (SOCE)

Curcumenol

Curcumenol, a sesquiterpene isolated from Curcuma zedoaria, is known to possess a variety of health and medicinal values which includes neuroprotection, anti-inflammatory, anti-tumor and hepatoprotective activities. It inhibits NF-κB activation by suppressing the nuclear translocation of the NF-κB p65 subunit and blocking IκBα phosphorylation and degradation.

Bergaptol

Bergaptol (5-Hydroxypsoralen, 5-Hydroxyfuranocoumarin) is a natural furanocoumarin found in the essential oils of citrus including lemon and bergamot.Bergaptol is a potent inhibitors of debenzylation activity of CYP3A4 enzyme with an IC50 value of 24.92 μM.

Ginsenoside F1

Ginsenoside F1, a pharmaceutical component of ginseng, is known to have antiaging, antioxidant, anticancer, and keratinocyte protective effects. Ginsenoside F1 exhibits competitive inhibition of the activity of CYP3A4 with Ki values of 67.8 ± 16.2 μM. Ginsenoside F1 also exhibited a weaker inhibition of the activity of CYP2D6.

Isosilybin

Isosilybin (Silymarin, Isosilybinin, Q-100795) is a flavanolignan found in the extract of S. marianum fruits with antioxidant and anticancer activities. Isosilybin inhibits CYP3A4 induction with an IC50 of 74 μM.

Posaconazole (SCH 56592)

Posaconazole (SCH 56592,POS,Noxafil) is an inhibitor primarily of CYP3A4, but it does not inhibit the activity of other CYP enzymes; Also an inhibitor of sterol C14ɑ demethylase inhibitor with IC50 of 0.25 μM. Posaconazole has a median terminal elimination half-life of 15-35 hours.

5,7-Dimethoxyflavone

5,7-Dimethoxyflavone (5,7-DMF) is an inhibitor of cytochrome P450 (CYP) 3As that markedly decreases the expression of CYP3A11 and CYP3A25 in the liver. 5,7-Dimethoxyflavone (5,7-DMF) is also a potent Breast Cancer Resistance Protein (BCRP, ABCG2) inhibitor. 5,7-Dimethoxyflavone (5,7-DMF) is one of the major components of Kaempferia parviflora with anti-obesity, anti-inflammatory, and antineoplastic effects.

Clarithromycin

Clarithromycin (A-56268) is a macrolide antibiotic and a CYP3A4 inhibitor, used to treat a number of bacterial infections.

Ritonavir

Ritonavir is a Cytochrome P450 3A and Protease Inhibitor; Also inhibits Cytochrome P450 2D6, P-Glycoprotein and induces Cytochrome P450 2C19, Cytochrome P450 1A2, Cytochrome P450 2C9, Cytochrome P450 2B6 and UDP Glucuronosyltransferases. Ritonavir induces apoptosis.

Piperine

Piperine (1-Piperoylpiperidine) is the alkaloid responsible for the pungency of black pepper and long pepper, which has also been used in some forms of traditional medicine and as an insecticide.

Cedrol

Cedrol, a natural occuring sesquiterpene alcohol, is a potent competitive inhibitor of CYP2B6-mediated bupropion hydroxylase with inhibition constant (Ki) value of 0.9 μM. It also inhibits CYP3A4-mediated midazolam hydroxylation with a Ki value of 3.4 μM while only weakly inhibits CYP2C8, CYP2C9, and CYP2C19 activities.

Pioglitazone HCl

Pioglitazone HCl (AD-4833, U-72107E) is an inhibitor of cytochrome P450 (CYP)2C8 and CYP3A4 enzymes. Pioglitazone HCl inhibits CYP2C8, CYP3A4 and CYP2C9 with Ki of 1.7 μM, 11.8 μM and 32.1 μM, respectively. Pioglitazone HCl is also a selective peroxisome proliferator-activated receptor-gamma (PPARγ) agonist with EC50 of 0.93 μM and 0.99 μM for human PPARγ and mouse PPARγ, respectively. Pioglitazone HCl inhibits mitochondrial iron uptake, lipid peroxidation, and subsequent

Ginsenoside Rd

Ginsenoside Rd (Panaxoside Rd, Sanchinoside Rd), a minor ginseng saponin, has several pharmacological activities such as immunosuppressive activity, anti-inflammatory activity, immunological adjuvant, anti-cancer activity and wound-healing activity. 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, CYP