cytochrome b

Atovaquone (Atavaquone) is a hydroxynaphthoquinone that has antimicrobial activity and is being used in antimalarial protocols.

BMS-903452 is a potent and selective GPR119 agonist with an EC50 of 14 nM, indicated for the treatment of acute and chronic rodent diabetes. GPR119 is mainly expressed in pancreatic b cells and gastrointestinal endocrine cells. BMS-903452 shows no significant inhibitory effect on 9 cytochrome P450 enzymes (IC50 > 40 μM), does not activate PXR (EC50 > 50 μM), and is not toxic to liver (HEPG2) cell lines.

Quinidine sulfate dihydrate (Pitayine Sodium) is a potent and selective cytochrome P450db inhibitor

Pyribencarb, a benzylcarbamate-type fungicide, exhibits broad-spectrum activity against various plant pathogenic fungi. Acting as a potent Qo inhibitor of cytochrome b, Pyribencarb demonstrates particular efficacy against Botrytis cinerea and Sclerotinia sclerotiorum.

RO6889678 is HBV inhibitor with a complex ADME profile.

Nampt-IN-5 is a potent and orally active inhibitor of nicotinamide phosphoribosyltransferase (NAMPT).

Pradefovir mesylate (Hepavir B) is converted to 9-(2-phosphonylmethoxyethyl)adenine (PMEA) in human liver microsomes with Km of 60 μM.

rac-trans-4-hydroxy Glyburide, an active metabolite of the SUR1 Kir6.2 sulfonylurea inhibitor glyburide, is formed by the cytochrome P450 (CYP) isoforms CYP2C8 and CYP2C9. It inhibits glyburide binding to rat brain synaptosomes at high and low affinity sites of SUR1 Kir6.2 with IC50 values of 0.95 and 100 nM, respectively.

Clindamycin sulfoxide, an active metabolite of the antibiotic clindamycin, is formed via S-oxidation primarily by the cytochrome P450 (CYP) isoform CYP3A4. It inhibits the growth of P. prevotti, B. fragilis, and C. sordelli in vitro with MIC values of 2, 2, and 1 mg L, respectively.

N-hydroxy Riluzole is a metabolite of the antiglutamatergic agent riluzole .1It is formed from riluzole predominantly by the cytochrome P450 (CYP) isoform CYP1A2 in human hepatic microsomes. 1.Sanderink, G.J., Bournique, B., Stevens, J., et al.Involvement of human CYP1A isoenzymes in the metabolism and drug interactions of riluzole in vitroJ. Pharmacol. Exp. Ther.282(3)1465-1472(1997)

17R(18S)-EpETE is an oxylipin and a cytochrome P450 metabolite of eicosapentaenoic acid .1,217R(18S)-EpETE is an activator of large-conductance calcium-activated potassium (BKCa) channels, increasing the potassium current amplitude by 15-fold in isolated rat cerebral artery vascular smooth muscle cells (VSMCs) at +60 mV when used at a concentration of 50 nM.2It has negative chronotropic effects in isolated neonatal rat cardiomyocytes (NRCMs; EC50= ~1-2 nM) and prevents calcium-induced increases in the spontaneous beating of NRCMs.3,4 1.Schwarz, D., Kisselev, P., Ericksen, S.S., et al.Arachidonic and eicosapentaenoic acid metabolism by human CYP1A1: Highly steroselective formation of 17(R), 18(S)-epoxyeicosatetraenoic acidBiochem. Pharmacol.67(8)1445-1457(2004) 2.Lauterbach, B., Barbosa-Sicard, E., Wang, M.H., et al.Cytochrome P450-dependent eicosapentaenoic acid metabolites are novel BK channel activatorsHypertension39(2 Pt. 2)609-613(2002) 3.Falck, J.R., Wallukat, G., Puli, N., et al.17(R),18(S)-Epoxyeicosatetraenoic acid, a potent eicosapentaenoic acid (EPA) derived regulator of cardiomyocyte contraction: Structure-activity relationships and stable analoguesJ. Med. Chem.54(12)4109-4118(2011) 4.Arnold, C., Markovic, M., Blossey, K., et al.Arachidonic acid-metabolizing cytochrome P450 enzymes are targets of omega-3 fatty acidsJ. Biol. Chem.285(43)32720-32733(2010)

Dehydro Nifedipine (BAY-b 4759) is the main metabolite of nifedipine in human plasma. Dehydro Nifedipine inhibits glucose uptake in PC-12 cells with an IC50 value of 130 μM. Nifedipine is a calcium channel blocker used in the treatment of hypertension and angina. Dehydronifedipine is formed when it is metabolized by cytochrome P450 (CYP) isomers CYP3A4 and CYP3A5.

Sorafenib N-oxide is an active metabolite of sorafenib , an inhibitor of Raf-1, B-RAF, and receptor tyrosine kinases. Sorafenib N-oxide inhibits FLT3 that contains the internal tandem duplication mutation (FLT3-ITD; Kd = 70 nM) and inhibits proliferation of MV4-11 acute myeloid leukemia (AML) cells expressing FLT3-ITD (IC50 = 25.8 nM). It is selective for AML cell lines containing FLT3-ITD over lines containing wild-type FLT3 (IC50s = 3.9-13.3 μM). Sorafenib N-oxide is also a linear-mixed inhibitor of the cytochrome P450 (CYP) isoform CYP3A4 (Ki = 15 μM in human liver microsomes).

7α-hydroxy Dehydroepiandrosterone (7α-hydroxy DHEA) is an active metabolite of the endogenous steroid hormone dehydroepiandrosterone .17α-hydroxy DHEA is formed from dehydroepiandrosteronevia7-hydroxylation by cytochrome P450s (CYPs).2It increases antigen-induced production of anti-tetanus toxoid and anti-pertussis antigen IgGs in co-cultures of human tonsil-derived B and T cells when used at a concentration of 1 μM.37α-hydroxy DHEA (6.25 mg/kg) increases serum concentrations of anti-lysozyme IgG in mice.1

Methyl protodioscin (Smilax saponin B) potentially increase HDL cholesterol while reducing LDL cholesterol and triglycerides. Methyl protodioscin has antitumor property. Methyl protodioscin induced apoptotic process in human A549 cells is closely associated with Mitochondrial membrane potential, caspase-3, and mitochondrial cytochrome c.

Picoxystrobin, a prominent primary strobilurin fungicide, is extensively utilized for efficient plant disease management. By obstructing electron transfer at the Qo center of cytochrome b and c1, picoxystrobin effectively halts mitochondrial respiration[1].

Q203 (Telacebec) is a novel potent anti-tuberculosis agent targeting cytochrome b subunit qcrB and inhibits M. tuberculosis H37Rv (MIC50: 2.7 nM).

β-Apo-8'-carotenal (Apocarotenal) is a carotenoid present in spinach and citrus fruits, utilized in fat-based foods (margarine, sauces, salad dressings), beverages, dairy products, and sweets.

1. Schisandrol B (Besigomsin) may exert neuroprotective effects by attenuating the microglia-mediated neuroinflammatory response via inhibiting the TLR4-mediated NF-κB and MAPKs signaling pathways. 2. Schisandrol B has anti-inflammatory property, potentially result from the inhibition of COX-2, iNOS, IL-6, TNF-α and NO through the down-regulation of RIP2 and NF-κB activation. 3. Schisandrol B induces marked protective effects against hepatic and renal injury induced by CCl(4) exposure through differential regulation of the MAPK signal transduction pathway. 4. Schisandrol B significantly inhibits cell proliferation in a dose-dependent manner, due to cell cycle arrest in the G1 phase with the downregulation of cyclin D1 expression and Retinoblastoma (RB) phosphorylation.

Azalanstat HCl is an anti-obesity drug acting as a lanosterol 14α-demethylase inhibitor. Azalanstat HCl has been shown to inhibit cholesterol synthesis in HepG2 cells, human fibroblasts, hamster hepatocytes and hamster liver, by inhibiting the cytochrome P450 enzyme lanosterol 14 alpha-demethylase. When administered orally to hamsters fed regular chow, RS-21607 (50 mg kg day) lowered serum cholesterol in a dose-dependent manner (ED50 = 62 mg kg) in a period of 1 week. It preferentially lowered low density lipoprotein (LDL) cholesterol and apo B relative to high density lipoprotein (HDL) cholesterol and apo A-1.

Azalanstat mesylate is an anti-obesity drug acting as a lanosterol 14α-demethylase inhibitor. Azalanstat mesylate has been shown to inhibit cholesterol synthesis in HepG2 cells, human fibroblasts, hamster hepatocytes and hamster liver, by inhibiting the cytochrome P450 enzyme lanosterol 14 alpha-demethylase. When administered orally to hamsters fed regular chow, RS-21607 (50 mg kg day) lowered serum cholesterol in a dose-dependent manner (ED50 = 62 mg kg) in a period of 1 week. It preferentially lowered low density lipoprotein (LDL) cholesterol and apo B relative to high density lipoprotein (HDL) cholesterol and apo A-1.

11α-Hydroxy Testosterone, a testosterone metabolite, is synthesized by the cytochrome P450 (CYP) isoform CYP3A.1, and can alternatively be produced from testosterone by a CYP107A1 mutant or from 11α-hydroxy progesterone by the fungus B. bassiana.2,3 The biological activity of 11α-Hydroxy Testosterone remains unclear.

N-Desmethyl Regorafenib N-oxide, an active metabolite of the multi-kinase inhibitor regorafenib, originates through the action of the cytochrome P450 (CYP) isoform CYP3A4. This compound demonstrates efficacy in vitro by inhibiting key enzymes such as VEGFR2, Tie2, c-Kit, and B-RAF, and it exhibits tumor growth inhibition in HT-29 and MDA-MB-231 mouse xenograft models at a dosage of 1 mg/kg.

Cyprocide-B is activated by Cytochrome P450, which converts it into an electrophilic metabolite that selectively kills the nematode C. elegans. This compound holds promise for research into selective nematicidal agents.