Genomes and Genes
Summary: Compounds that bind to and inhibit that enzymatic activity of LIPOXYGENASES. Included under this category are inhibitors that are specific for lipoxygenase subtypes and act to reduce the production of LEUKOTRIENES.
- Tardif J, L Allier P, Ibrahim R, Grégoire J, Nozza A, Cossette M, et al. Treatment with 5-lipoxygenase inhibitor VIA-2291 (Atreleuton) in patients with recent acute coronary syndrome. Circ Cardiovasc Imaging. 2010;3:298-307 pubmed publisher..Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00358826. ..
- Altavilla D, Squadrito F, Bitto A, Polito F, Burnett B, Di Stefano V, et al. Flavocoxid, a dual inhibitor of cyclooxygenase and 5-lipoxygenase, blunts pro-inflammatory phenotype activation in endotoxin-stimulated macrophages. Br J Pharmacol. 2009;157:1410-8 pubmed publisher..Finally, flavocoxid decreased MDA, TNF and nitrite levels from LPS-stimulated macrophages. Flavocoxid might be useful as a potential anti-inflammatory agent, acting at the level of gene and protein expression. ..
- Ding X, Zhu C, Qiang H, Zhou X, Zhou G. Enhancing antitumor effects in pancreatic cancer cells by combined use of COX-2 and 5-LOX inhibitors. Biomed Pharmacother. 2011;65:486-90 pubmed publisher..Our results imply that combined use of celecoxib and MK886 might be an effective way to treat clinical patients with pancreatic cancer. ..
- Czapski G, Czubowicz K, Strosznajder R. Evaluation of the antioxidative properties of lipoxygenase inhibitors. Pharmacol Rep. 2012;64:1179-88 pubmed..AA-861, whose antioxidative potential is very weak, may be a specific tool to be used in experimental and perhaps even clinical applications. ..
- Yu S, Kuhn H, Daniliuc C, Ivanov I, Jones P, du Mont W. 5-Selenization of salicylic acid derivatives yielded isoform-specific 5-lipoxygenase inhibitors. Org Biomol Chem. 2010;8:828-34 pubmed publisher..In addition, synthesis products exhibited GPx-like activity, which was higher than that of ebselen for some derivatives...
- Rossi A, Pergola C, Koeberle A, Hoffmann M, Dehm F, Bramanti P, et al. The 5-lipoxygenase inhibitor, zileuton, suppresses prostaglandin biosynthesis by inhibition of arachidonic acid release in macrophages. Br J Pharmacol. 2010;161:555-70 pubmed publisher..Zileuton inhibited PG production by interfering at the level of AA release. Its mechanism of action, as well as its use as a pharmacological tool, in experimental models of inflammation should be reassessed. ..
- Ngu K, Weinstein D, Liu W, Langevine C, Combs D, Zhuang S, et al. Pyrazole-based sulfonamide and sulfamides as potent inhibitors of mammalian 15-lipoxygenase. Bioorg Med Chem Lett. 2011;21:4141-5 pubmed publisher..Replacement of a sulfonamide functionality in the lead series with a sulfamide group resulted in improved physicochemical properties generating analogs with enhanced inhibition in cell-based and whole blood assays. ..
- Doiron J, Boudreau L, Picot N, Villebonet B, Surette M, Touaibia M. Synthesis and 5-lipoxygenase inhibitory activity of new cinnamoyl and caffeoyl clusters. Bioorg Med Chem Lett. 2009;19:1118-21 pubmed publisher..Caffeoyl cluster showed an improved 5-lipoxygenase inhibitory activity compared to caffeic acid, with caffeoyl trimer 16 and tetramer 19 showing the best 5-lipoxygenase inhibitory activity. ..
- Gleissman H, Yang R, Martinod K, Lindskog M, Serhan C, Johnsen J, et al. Docosahexaenoic acid metabolome in neural tumors: identification of cytotoxic intermediates. FASEB J. 2010;24:906-15 pubmed publisher..Gleissman, H., Yang, R., Martinod, K., Lindskog, M., Serhan, C. N., Johnsen, J. I., Kogner, P. Docosahexaenoic acid metabolome in neural tumors: identification of cytotoxic intermediates. ..
- Morin P, Ferguson D, Leblanc L, Hébert M, Paré A, Jean Francois J, et al. NMR metabolomics analysis of the effects of 5-lipoxygenase inhibitors on metabolism in glioblastomas. J Proteome Res. 2013;12:2165-76 pubmed publisher..of metabolic profiles was used to investigate the response of glioblastoma cell lines to treatment with 5-lipoxygenase inhibitors. Metabolic profiling of cells following drug treatment provides valuable information about the response ..
- Polito F, Bitto A, Irrera N, Squadrito F, Fazzari C, Minutoli L, et al. Flavocoxid, a dual inhibitor of cyclooxygenase-2 and 5-lipoxygenase, reduces pancreatic damage in an experimental model of acute pancreatitis. Br J Pharmacol. 2010;161:1002-11 pubmed publisher..Flavocoxid may provide a potential therapeutic approach to the treatment of patients at high risk of developing this life-threatening condition. ..
- Wu Y, He C, Gao Y, He S, Liu Y, Lai L. Dynamic modeling of human 5-lipoxygenase-inhibitor interactions helps to discover novel inhibitors. J Med Chem. 2012;55:2597-605 pubmed publisher..The compounds reported here provide new scaffolds for anti-inflammatory drug design. ..
- Fischer A, Metzner J, Steinbrink S, Ulrich S, Angioni C, Geisslinger G, et al. 5-Lipoxygenase inhibitors induce potent anti-proliferative and cytotoxic effects in human tumour cells independently of suppression of 5-lipoxygenase activity. Br J Pharmacol. 2010;161:936-49 pubmed publisher..Certain 5-LO inhibitors cause cytotoxic and anti-proliferative effects independently of suppression of 5-LO activity. Thus, the role of 5-LO overexpression in tumour cell viability remains unclear and requires further elucidation. ..
- Czubowicz K, Czapski G, Cieslik M, Strosznajder R. Lipoxygenase inhibitors protect brain cortex macromolecules against oxidation evoked by nitrosative stress. Folia Neuropathol. 2010;48:283-92 pubmed..5 ?M demonstrated antioxidative properties. These results should be taken into consideration during evaluation of experimental and clinical effects of LOX inhibitors. ..
- Kaur J, Bhardwaj A, Huang Z, Knaus E. Aspirin analogues as dual cyclooxygenase-2/5-lipoxygenase inhibitors: synthesis, nitric oxide release, molecular modeling, and biological evaluation as anti-inflammatory agents. ChemMedChem. 2012;7:144-50 pubmed publisher..4. Molecular docking studies in the active binding site of COX-2 and 5-LOX provided complementary theoretical support for the experimental biological structure-activity data acquired. ..
- Sarveswaran S, Thamilselvan V, Brodie C, Ghosh J. Inhibition of 5-lipoxygenase triggers apoptosis in prostate cancer cells via down-regulation of protein kinase C-epsilon. Biochim Biophys Acta. 2011;1813:2108-17 pubmed publisher..Altogether, these findings suggest that metabolism of arachidonic acid by 5-LOX activity promotes survival of prostate cancer cells via signaling through PKC?, a pro-survival serine/threonine kinase. ..
- Aparoy P, Kumar Reddy K, Kalangi S, Chandramohan Reddy T, Reddanna P. Pharmacophore modeling and virtual screening for designing potential 5-lipoxygenase inhibitors. Bioorg Med Chem Lett. 2010;20:1013-8 pubmed publisher..These studies thus validate the pharmacophore model generated and suggest the usefulness of the model in screening of various small molecule libraries and identification of potential lead compounds for 5-LOX inhibition. ..
- Yigitkanli K, Pekcec A, Karatas H, Pallast S, Mandeville E, Joshi N, et al. Inhibition of 12/15-lipoxygenase as therapeutic strategy to treat stroke. Ann Neurol. 2013;73:129-35 pubmed publisher..Furthermore, it reduced tissue plasminogen activator-associated hemorrhage in a clot model of ischemia/reperfusion. This study establishes inhibition of 12/15-lipoxygenase as a viable strategy for first-line stroke treatment. ..
- Kenyon V, Rai G, Jadhav A, Schultz L, Armstrong M, Jameson J, et al. Discovery of potent and selective inhibitors of human platelet-type 12- lipoxygenase. J Med Chem. 2011;54:5485-97 pubmed publisher..In addition, these compounds demonstrate efficacy in cellular models, which underscores their relevance to disease modification. ..
- Redova M, Chlapek P, Loja T, Zitterbart K, Hermanova M, Sterba J, et al. Influence of LOX/COX inhibitors on cell differentiation induced by all-trans retinoic acid in neuroblastoma cell lines. Int J Mol Med. 2010;25:271-80 pubmed..Nevertheless, further detailed study of the phenomenon of enhanced cell differentiation by expression profiling is needed. ..
- Robinson S, Hoobler E, Riener M, Loveridge S, Tenney K, Valeriote F, et al. Using enzyme assays to evaluate the structure and bioactivity of sponge-derived meroterpenes. J Nat Prod. 2009;72:1857-63 pubmed publisher..Significant potency and selectivity profiles were exhibited in the human 5-lipoxygenase assay by puupehenone (1) and jaspaquinol (9) and structural factors responsible for activity identified...
- Chen Y, Li D, Li S. The Alox5 gene is a novel therapeutic target in cancer stem cells of chronic myeloid leukemia. Cell Cycle. 2009;8:3488-92 pubmed..Specific targeting of CSCs without causing significant harm to normal stem cells should be a correct direction to go in developing novel therapeutic strategies in the future. ..
- Pallast S, Arai K, Wang X, Lo E, van Leyen K. 12/15-Lipoxygenase targets neuronal mitochondria under oxidative stress. J Neurochem. 2009;111:882-9 pubmed publisher..These findings position 12/15-LOX as the central executioner in an oxidative stress-related neuronal death program. ..
- Pergola C, Jazzar B, Rossi A, Buehring U, Luderer S, Dehm F, et al. Cinnamyl-3,4-dihydroxy-?-cyanocinnamate is a potent inhibitor of 5-lipoxygenase. J Pharmacol Exp Ther. 2011;338:205-13 pubmed publisher..Together, our data demonstrate that CDC is a potent inhibitor of 5-LO with efficacy in vivo and encourage further development of CDC as the lead compound. ..
- Levy R, Khokhlov A, Kopenkin S, Bart B, Ermolova T, Kantemirova R, et al. Efficacy and safety of flavocoxid, a novel therapeutic, compared with naproxen: a randomized multicenter controlled trial in subjects with osteoarthritis of the knee. Adv Ther. 2010;27:731-42 pubmed publisher..Flavocoxid demonstrated better UGI, renal (edema), and respiratory safety profiles than naproxen. ..
- Tan C, Chen G, Chen C, Chang P, Chern J. Design, synthesis and biological evaluation of benzo[1.3.2]dithiazolium ylide 1,1-dioxide derivatives as potential dual cyclooxygenase-2/5-lipoxygenase inhibitors. Bioorg Med Chem. 2011;19:6316-28 pubmed publisher..As a result, benzo[1.3.2]dithiazolium ylide 1,1-dioxide represented a novel scaffold for the exploitation in developing dual COX-2/5-LOX inhibitors. ..
- Masferrer J, Zweifel B, Hardy M, Anderson G, Dufield D, Cortes Burgos L, et al. Pharmacology of PF-4191834, a novel, selective non-redox 5-lipoxygenase inhibitor effective in inflammation and pain. J Pharmacol Exp Ther. 2010;334:294-301 pubmed publisher..The combination of potency in cells and in vivo, together with a sustained in vivo effect, provides PF-4191834 with an overall pharmacodynamic improvement consistent with once a day dosing. ..
- Hofmann B, Barzen S, Rödl C, Kiehl A, Borig J, Zivkovic A, et al. A class of 5-benzylidene-2-phenylthiazolinones with high potency as direct 5-lipoxygenase inhibitors. J Med Chem. 2011;54:1943-7 pubmed publisher..28 and 0.09 ?M). These disubstituted thiazolinones may possess potential for intervention with inflammatory and allergic diseases and certain cancer types. ..
- Reddy N, Aparoy P, Reddy T, Achari C, Sridhar P, Reddanna P. Design, synthesis, and biological evaluation of prenylated chalcones as 5-LOX inhibitors. Bioorg Med Chem. 2010;18:5807-15 pubmed publisher..Further, the compound 5e showed potent anti-proliferative effects (GI(50) at 9 microM) on breast cancer cell line, MCF-7. ..
- Bajgai S, Prachyawarakorn V, Mahidol C, Ruchirawat S, Kittakoop P. Hybrid flavan-chalcones, aromatase and lipoxygenase inhibitors, from Desmos cochinchinensis. Phytochemistry. 2011;72:2062-7 pubmed publisher..9, and 0.8 ?M. Desmosflavan A (1) inhibited lipoxygenase with the IC50 value of 4.4 ?M. Desmosflavan A (1) exhibited cytotoxic activity with IC50 values of 0.29-3.75 ?g/mL, while desmosflavan B (2) showed IC50 values of 1.71-27.0 ?g/mL. ..
- Yu G, Chowdhury M, Abdellatif K, Dong Y, Praveen Rao P, Das D, et al. Phenylacetic acid regioisomers possessing a N-difluoromethyl-1,2-dihydropyrid-2-one pharmacophore: evaluation as dual inhibitors of cyclooxygenases and 5-lipoxygenase with anti-inflammatory activity. Bioorg Med Chem Lett. 2010;20:896-902 pubmed publisher..Accordingly, the N-difluoromethyl-1,2-dihyrdopyrid-2-one moiety possesses properties that make it an attractive pharmacophore suitable for the design of dual COX-2/5-LOX inhibitory AI drugs. ..
- Ishii K, Zaitsu M, Yonemitsu N, Kan Y, Hamasaki Y, Matsuo M. 5-lipoxygenase pathway promotes cell proliferation in human glioma cell lines. Clin Neuropathol. 2009;28:445-52 pubmed..The 5-LO-LTA4 pathway might play roles in the proliferation of human glioma cells. ..
- Aparoy P, Suresh G, Kumar Reddy K, Reddanna P. CoMFA and CoMSIA studies on 5-hydroxyindole-3-carboxylate derivatives as 5-lipoxygenase inhibitors: generation of homology model and docking studies. Bioorg Med Chem Lett. 2011;21:456-62 pubmed publisher..The 3D-QSAR models were compared with the interactions at the active site to further elucidate the accuracy of the models. The data generated from 3D-QSAR study was used to design potential 5-LOX inhibitors. ..
- Pergola C, Werz O. 5-Lipoxygenase inhibitors: a review of recent developments and patents. Expert Opin Ther Pat. 2010;20:355-75 pubmed publisher..Despite the increasing therapeutic indications of anti-LT therapy, the progress in the development of novel 5-LO inhibitors is moderate. However, novel molecular concepts in the intervention with LT biosynthesis seem promising. ..
- Schwarz O, Jakupovic S, Ambrosi H, Haustedt L, Mang C, Müller Kuhrt L. Natural products in parallel chemistry--novel 5-lipoxygenase inhibitors from BIOS-based libraries starting from alpha-santonin. J Comb Chem. 2007;9:1104-13 pubmed..After application of a fingerprint-based virtual screening on these compounds, the biological screening of 23 selected library members against 5-lipoxygenase resulted in the discovery of four potent novel inhibitors of this enzyme. ..
- Yoshimura R, Inoue K, Kawahito Y, Mitsuhashi M, Tsuchida K, Matsuyama M, et al. Expression of 12-lipoxygenase in human renal cell carcinoma and growth prevention by its inhibitor. Int J Mol Med. 2004;13:41-6 pubmed..These results suggest 12-LOX may play a role in the progression of RCC in human tissue, and its inhibitors may become anticancer agents in human RCC. ..
- Tavolari S, Bonafe M, Marini M, Ferreri C, Bartolini G, Brighenti E, et al. Licofelone, a dual COX/5-LOX inhibitor, induces apoptosis in HCA-7 colon cancer cells through the mitochondrial pathway independently from its ability to affect the arachidonic acid cascade. Carcinogenesis. 2008;29:371-80 pubmed
- Kälvegren H, Andersson J, Grenegård M, Bengtsson T. Platelet activation triggered by Chlamydia pneumoniae is antagonized by 12-lipoxygenase inhibitors but not cyclooxygenase inhibitors. Eur J Pharmacol. 2007;566:20-7 pubmed..The findings in this study showing that platelets stimulated by C. pneumoniae are unaffected by COX inhibitors but sensitive to 12-LOX inhibitors, may thus be of importance in future management of atherosclerosis and thrombosis. ..
- Werz O, Steinhilber D. Therapeutic options for 5-lipoxygenase inhibitors. Pharmacol Ther. 2006;112:701-18 pubmed..In this review, we summarize the knowledge on possible functions of the 5-LO pathway in various diseases like asthma, cancer and cardiovascular events and review the corresponding potential therapeutic roles of 5-LO inhibitors. ..
- Mano T, Okumura Y, Sakakibara M, Okumura T, Tamura T, Miyamoto K, et al. 4-[5-Fluoro-3-[4-(2-methyl-1H-imidazol-1-yl)benzyloxy]phenyl]-3,4,5,6- tetrahydro-2H-pyran-4-carboxamide, an orally active inhibitor of 5-lipoxygenase with improved pharmacokinetic and toxicology characteristics. J Med Chem. 2004;47:720-5 pubmed..Enhanced metabolic stability resulted in fewer in vivo metabolites, as well as improved bioavailability and a better toxicological profile. Thus, 10 was found to be a more practical lead for an orally active 5-LO inhibitor. ..
- Rotondo S, Krauze Brzósko K, Manarini S, Evangelista V, Cerletti C. Licofelone, an inhibitor of cyclooxygenase and 5-lipoxygenase, specifically inhibits cyclooxygenase-1-dependent platelet activation. Eur J Pharmacol. 2004;488:79-83 pubmed..These results indicate that, at clinically relevant concentrations, licofelone exerts a potent antiplatelet effect mediated by the inhibition of cyclooxygenase-1 activity. ..
- Cichewicz R, Kenyon V, Whitman S, Morales N, Arguello J, Holman T, et al. Redox inactivation of human 15-lipoxygenase by marine-derived meroditerpenes and synthetic chromanes: archetypes for a unique class of selective and recyclable inhibitors. J Am Chem Soc. 2004;126:14910-20 pubmed..This pharmacophore represents a promising paradigm for the development of a unique class of recyclable 15-hLO redox inhibitors for the treatment of atherosclerosis. ..
- Ahmad I, Nawaz S, Afza N, Malik A, Fatima I, Khan S, et al. Isolation of onosmins A and B, lipoxygenase inhibitors from Onosma hispida. Chem Pharm Bull (Tokyo). 2005;53:907-10 pubmedOnosmins A (1) and B (2), lipoxygenase inhibitors, have been isolated from Onosma hispida...
- Wada K, Arita M, Nakajima A, Katayama K, Kudo C, Kamisaki Y, et al. Leukotriene B4 and lipoxin A4 are regulatory signals for neural stem cell proliferation and differentiation. FASEB J. 2006;20:1785-92 pubmed..These results indicate for the first time that LTB(4) and LXA(4) directly regulate proliferation and differentiation of NSCs, suggesting these new pathways may be useful in restoring stem cells. ..
- Flamand N, Lefebvre J, Surette M, Picard S, Borgeat P. Arachidonic acid regulates the translocation of 5-lipoxygenase to the nuclear membranes in human neutrophils. J Biol Chem. 2006;281:129-36 pubmed..This report demonstrates that AA regulates the translocation of 5-LO in human PMN and unravels a novel mechanism of the cAMP-mediated inhibition of LT biosynthesis. ..
- Cianchi F, Cortesini C, Magnelli L, Fanti E, Papucci L, Schiavone N, et al. Inhibition of 5-lipoxygenase by MK886 augments the antitumor activity of celecoxib in human colon cancer cells. Mol Cancer Ther. 2006;5:2716-26 pubmed..In conclusion, our study showed that inhibition of 5-LOX by MK886 could augment the antitumor activity of celecoxib in human colorectal cancer. ..
- Aparoy P, Reddy R, Guruprasad L, Reddy M, Reddanna P. Homology modeling of 5-lipoxygenase and hints for better inhibitor design. J Comput Aided Mol Des. 2008;22:611-9 pubmed publisher..Our results correlated well with the experimental data reported earlier, which proved the quality of the model. This model generated can be further used for the design and development of more potent 5-LOX inhibitors. ..
- Dahlen S. Treatment of asthma with antileukotrienes: first line or last resort therapy?. Eur J Pharmacol. 2006;533:40-56 pubmed..Further research needs and new areas for leukotriene involvement in respiratory diseases are also discussed. ..
- van Leyen K, Arai K, Jin G, Kenyon V, Gerstner B, Rosenberg P, et al. Novel lipoxygenase inhibitors as neuroprotective reagents. J Neurosci Res. 2008;86:904-9 pubmed..Future studies of these novel neuroprotective inhibitors of 12/15-LOX may provide new therapeutic opportunities to combat stroke and other neurodegenerative diseases. ..
- Chen X, Wang S, Wu N, Sood S, Wang P, Jin Z, et al. Overexpression of 5-lipoxygenase in rat and human esophageal adenocarcinoma and inhibitory effects of zileuton and celecoxib on carcinogenesis. Clin Cancer Res. 2004;10:6703-9 pubmed..Both zileuton and celecoxib had inhibitory effects on esophageal adenocarcinogenesis through inhibition on their respective enzymes of AA metabolism. ..
- Knaup B, Oehme A, Valotis A, Schreier P. Anthocyanins as lipoxygenase inhibitors. Mol Nutr Food Res. 2009;53:617-24 pubmed publisher..Considering the powerful inhibitory properties of Dp glycosides in relation to their currently known availability in human metabolism, in vivo prevention of inflammatory diseases by these anthocyanins could be envisaged. ..