Enzyme inhibitors

Formononetin is a phytoestrogen from the root of Astragalus membranaceus and an O-methylated isoflavone. It displays a wide variety of biological activityes, including decreasing expression of pro-imflammatory cytokines, inducing apoptosis in prostate cancer cells, lowering systolic blood pressure and inhibiting attachment and motility of Giardia.

Dabrafenib (GSK2118436) is a mutant BRAFV600 specific inhibitor with IC50 of 0.8 nM, with 4- and 6-fold less potency against B-Raf(wt) and c-Raf, respectively.

Ditryptophenaline is an alkaloid metabolite of Aspergillus flavus. Ditryptophenaline exhibits potential analgesic and anti-inflammatory activities. It is a tachykinin antagonist.

Demethoxyfumitremorgin C is a metabolite of Aspergillus fumigatus. Demethoxyfumitremorgin C acts as a fungal inhibitor of mammalian cell cycle progression at the G(2)/M transition.

Chelerythrine is a cell-permeable inhibitor of protein kinase C (IC50 = 660 nM) with a wide range of biological activities.

Colchicine, a toxic plant-derived alkaloid extracted from plants of the genus Colchicum, inhibits microtubule polymerization (IC50 = 3.2 μM). It inhibits the growth of MCF-7 human breast carcinoma cells and has anti-inflammatory activity. Colchicine can lower body temperature, inhibit the respiratory center, enhance the effect of sympathomimetic drugs, constrict blood vessels, and raise blood pressure.

Fluconazole is a triazole antifungal agent that is effective against most Candida strains. Fluconazole is a fungal lanosterol 14 alpha-demethylase inhibitor used in the treatment and prevention of superficial and systemic fungal infections.

Moxifloxacin exerts its effects by trapping a DNA drug enzyme complex and specifically inhibiting ATP-dependent enzymes topoisomerase II (DNA gyrase) and topoisomerase IV. It is a fluoroquinolone antibiotic with broad-spectrum bactericidal activity against gram-positive and gram-negative strains.

Penicillamine is used as an antirheumatic and as a chelating agent in Wilson's disease.

Bestatin is a specific aminopeptidase B inhibitor produced by Streptomyces olivoreticuli. Bestatin is a potent aminopeptidase-B and leukotriene (LT) A4 hydrolase inhibitor used in the treatment of acute myelocytic leukemia. It exhibits potential immunomodulatory and antitumor activities.

Anidulafungin, is a semisynthetic echinocandin that inhibits glucan synthase, an enzyme important in the formation of (1→3)-β-D-glucan, a major fungal cell wall component, and thus is used as an antifungal drug.

Lamivudine is a potent nucleoside analog reverse transcriptase inhibitor, used for treatment of chronic HBV and HIV/AIDS.

Entecavir triphosphate is a highly potent inhibitor of wild-type HBV Pol and is 100- to 300-fold more potent than lamivudine triphosphate against 3TC-resistant HBV Pol. It competes with dGTP to be incorporated into viral DNA.

Midostaurin is a multi-target protein kinase inhibitor being investigated for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). It is a semi-synthetic derivative of staurosporine, an alkaloid from the bacterium Streptomyces staurosporeus.

Clavulanate Potassium is a semi-synthetic beta-lactamase inhibitor isolated from streptomyces. It contains a beta-lactam ring and binds strongly to beta-lactamase at or near its active site. It is used in conjunction with beta-lactamase susceptible penicillins to treat infections caused by beta-lactamase producing organisms. It is commonly combined with amoxicillin or ticarcillin to increase its effectiveness.

Pravastatin sodium is an HMG-CoA reductase inhibitor against sterol synthesis with IC50 of 5.6 μM.

Omeprazole is a proton pump inhibitor used in the treatment of dyspepsia. It binds to the proton pump hydrogen-potassium adenosine triphosphatase (H+/K+ ATPase) and inhibits its activity and the parietal cell secretion of H+ ions into the gastric lumen.

Everolimus is an inhibitor of mammalian target of rapamycin (mTOR) with an immunosuppressive activity which is comparable to that of rapamycin. It inhibits cytokine-mediated lymphocyte proliferation. Everolimus can be used as an immunosuppressant in the treatment of renal cell cancer and other cancers.

Cidofovir is an injectable antiviral medication for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS. It suppresses CMV replication by selective inhibition of viral DNA polymerase and therefore prevention of viral replication and transcription. It is an acyclic nucleoside phosphonate, and is therefore independent of phosphorylation by viral enzymes, unlike acyclovir. Cidofovir was discovered at the Institute of Organic Chemistry and Biochemistry, Prague, and developed by Gilead Sciences and is marketed with the brand name Vistide by Gilead in the USA, and by Pfizer elsewhere. Maintenance therapy with cidofovir involves an infusion only once every two weeks, making it a convenient treatment option. Because dosing is relatively infrequent, a permanent catheter is not necessary for infusions.

Erlotinib HCl potently inhibits EGFR activation in intact cells including HNS human head and neck tumor cells (IC50 = 20 nM), DiFi humancolon cancer cells and MDA MB-468 human breast cancer cells.