Target Information

Target General Infomation
Target ID
T73726
Former ID
TTDS00359
Target Name
Fungal Cytochrome P450 51
Gene Name
ERG11
Synonyms
CYPL1; CYPLI; Cyt P450 14DM; Cytochrome P-450 lanosterol 14-alpha-demethylase; Cytochrome P450-dependent lanosterol 14-demethylase; Erg11p; LDM; Lanosterol 14 alpha-demethylase; Lanosterol 14-alpha demethylase; P450-14DM; P450L1; P450LI; Sterol 14-alpha demethylase; Sterol 14alpha-demethylase; ERG11
Target Type
Successful
Disease Aspergillosis [ICD10: B44]
Candidiasis infection [ICD9: 001-139, 112; ICD10: B37]
Chronic pain [ICD9: 338.2,780; ICD10: R52.1-R52.2, G89]
Dry eye disease [ICD9: 370.33; ICD10: H16.229]
Dermatological disease [ICD10: L00-L99]
Fungal infections [ICD9: 110-118; ICD10: B35-B49]
Hyperlipidaemia [ICD9: 272.0-272.4; ICD10: E78]
Invasive aspergillosis [ICD9: 117.3; ICD10: B44]
Onychomycosis [ICD10: B35.1]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Tinea pedis [ICD10: B35.6]
Tinea pedis; Tinea cruris; Tinea corporis; Cutaneous candidiasis; Tinea versicolor [ICD10: B353]
Function
Catalyzes C14-demethylation of lanosterol which is critical for ergosterol biosynthesis. It transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.
BioChemical Class
Oxidoreductases acting on paired donors
Target Validation
T73726
UniProt ID
P10613
EC Number
EC 1.14.13.70
Sequence
MAIVETVIDGINYFLSLSVTQQISILLGVPFVYNLVWQYLYSLRKDRAPLVFYWIPWFGS
AASYGQQPYEFFESCRQKYGDVFSFMLLGKIMTVYLGPKGHEFVFNAKLSDVSAEDAYKH
LTTPVFGKGVIYDCPNSRLMEQKKFAKFALTTDSFKRYVPKIREEILNYFVTDESFKLKE
KTHGVANVMKTQPEITIFTASRSLFGDEMRRIFDRSFAQLYSDLDKGFTPINFVFPNLPL
PHYWRRDAAQKKISATYMKEIKSRRERGDIDPNRDLIDSLLIHSTYKDGVKMTDQEIANL
LIGILMGGQHTSASTSAWFLLHLGEKPHLQDVIYQEVVELLKEKGGDLNDLTYEDLQKLP
SVNNTIKETLRMHMPLHSIFRKVTNPLRIPETNYIVPKGHYVLVSPGYAHTSERYFDNPE
DFDPTRWDTAAAKANSVSFNSSDEVDYGFGKVSKGVSSPYLPFGGGRHRCIGEQFAYVQL
GTILTTFVYNLRWTIDGYKVPDPDYSSMVVLPTEPAEIIWEKRETCMF
Structure
4LXJ
Drugs and Mode of Action
Drug(s) Bifonazole Drug Info Approved Fungal infections [550663]
Butoconazole Drug Info Approved Candidiasis infection [538547], [551871]
Econazole Drug Info Approved Tinea pedis; Tinea cruris; Tinea corporis; Cutaneous candidiasis; Tinea versicolor [551871]
Efinaconazole Drug Info Approved Fungal infections [533086]
Fluconazole Drug Info Approved Fungal infections [537641]
Itraconazole Drug Info Approved Fungal infections [538311]
Ketoconazole Drug Info Approved Fungal infections [538296], [539659]
Luliconazole Drug Info Approved Tinea pedis [532651], [542388], [551871]
Miconazole Drug Info Approved Fungal infections [538319], [539577]
Oxiconazole Drug Info Approved Tinea pedis [538534], [551871]
Posaconazole Drug Info Approved Aspergillosis [528715], [530959], [538580]
Sertaconazole Drug Info Approved Fungal infections [538564]
Terconazole Drug Info Approved Candidiasis infection [538573], [551871]
Tioconazole Drug Info Approved Onychomycosis [538305], [551871]
Voriconazole Drug Info Approved Invasive aspergillosis [537601]
CHLORIDE Drug Info Phase 3 Solid tumours [533218], [539483]
Econazole Drug Info Phase 3 Chronic pain [532876]
Luliconazole 10% Drug Info Phase 2/3 Dry eye disease [523617], [551740]
E-1224 Drug Info Phase 2 Fungal infections [523720]
EcoNail Drug Info Phase 2 Fungal infections [521897]
Pramiconazole Drug Info Phase 2 Dermatological disease [528869]
Embeconazole Drug Info Phase 1 Fungal infections [547271]
Genaconazole Drug Info Phase 1 Fungal infections [531676]
Abafungin Drug Info Discontinued in Phase 3 Fungal infections [548190]
AZALANSTAT Drug Info Discontinued in Phase 2 Hyperlipidaemia [545151]
Inhibitor Abafungin Drug Info [527740]
ANALOGUE A Drug Info [528602]
Bifonazole Drug Info [536289], [537801], [537803]
Butoconazole Drug Info [537667]
CP-320626 Drug Info [528602]
E-1224 Drug Info [532173]
EcoNail Drug Info [531032]
Econazole Drug Info [536809]
Efinaconazole Drug Info [533086], [551871]
Embeconazole Drug Info [549777]
Ketoconazole Drug Info [537556]
Luliconazole Drug Info [532651], [551871]
Oxiconazole Drug Info [535752], [536275]
Posaconazole Drug Info [536273]
Sertaconazole Drug Info [537139]
Terconazole Drug Info [537454]
Tioconazole Drug Info [536031]
Modulator AZALANSTAT Drug Info
CHLORIDE Drug Info [533218]
Fluconazole Drug Info [556264]
Genaconazole Drug Info [525976]
Itraconazole Drug Info [556264]
Luliconazole 10% Drug Info
Miconazole Drug Info [556264]
Pramiconazole Drug Info [1572591]
Voriconazole Drug Info [556264]
Binder FLC Drug Info [535932]
References
Ref 521897ClinicalTrials.gov (NCT00385502) A Trial of the Safety and Efficacy of EcoNail in the Treatment of Fungus Infections of the Great Toenail. U.S. National Institutes of Health.
Ref 523617ClinicalTrials.gov (NCT01431820) Safety and Efficacy of Luliconazole Solution, 10% in Subjects With Mild to Moderate Onychomycosis. U.S. National Institutes of Health.
Ref 523720ClinicalTrials.gov (NCT01489228) Proof-of-Concept Study of E1224 to Treat Adult Patients With Chagas Disease. U.S. National Institutes of Health.
Ref 5287152006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
Ref 528869The efficacy of oral treatment with pramiconazole in pityriasis versicolor: a phase II a trial. Br J Dermatol. 2007 Jun;156(6):1385-8.
Ref 530959Structural insights into inhibition of sterol 14alpha-demethylase in the human pathogen Trypanosoma cruzi. J Biol Chem. 2010 Aug 13;285(33):25582-90.
Ref 531676In vivo efficacy of SM-8668 (Sch 39304), a new oral triazole antifungal agent. Antimicrob Agents Chemother. 1990 Jun;34(6):980-4.
Ref 5326512013 FDA drug approvals. Nat Rev Drug Discov. 2014 Feb;13(2):85-9.
Ref 532876Econazole nitrate foam 1% for the treatment of tinea pedis: results from two double-blind, vehicle-controlled, phase 3 clinical trials. J Drugs Dermatol. 2014 Jul;13(7):803-8.
Ref 533086Efinaconazole: Developmental and reproductive toxicity potential of a novel antifungal azole. Reprod Toxicol. 2015 Apr;52:18-25.
Ref 533218Isavuconazonium: first global approval. Drugs. 2015 May;75(7):817-22.
Ref 537601Disk diffusion test and E-test with enriched Mueller-Hinton agar for determining susceptibility of Candida species to voriconazole and fluconazole. J Microbiol Immunol Infect. 2009 Apr;42(2):148-53.
Ref 537641Fluconazole use as an important risk factor in the emergence of fluconazole-resistant Candida glabrata fungemia. Arch Intern Med. 2009 Aug 10;169(15):1444-5; author reply 1445.
Ref 538296FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 075273.
Ref 538305FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 075915.
Ref 538311FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 076104.
Ref 538319FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 076773.
Ref 538534FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 019828.
Ref 538547FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 020421.
Ref 538564FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 021385.
Ref 538573FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 021735.
Ref 538580FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 022003.
Ref 539483(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2339).
Ref 539577(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2449).
Ref 539659(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2568).
Ref 542388(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7366).
Ref 545151Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002302)
Ref 547271Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014655)
Ref 548190Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022887)
Ref 550663Drug information of Bifonazole, 2008. eduDrugs.
Ref 551740Clinical pipeline report, company report or official report of Topica Pharmaceuticals.
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref
Ref 525976New targets and delivery systems for antifungal therapy. Med Mycol. 2000;38 Suppl 1:335-47.
Ref 527740Upregulation of sterol C14-demethylase expression in Trypanosoma cruzi treated with sterol biosynthesis inhibitors. Mol Biochem Parasitol. 2005 Nov;144(1):68-75.
Ref 528602Drug Metab Dispos. 2007 Mar;35(3):493-500. Epub 2006 Dec 28.Three-dimensional quantitative structure-activity relationship analysis of human CYP51 inhibitors.
Ref 531032Azole binding properties of Candida albicans sterol 14-alpha demethylase (CaCYP51). Antimicrob Agents Chemother. 2010 Oct;54(10):4235-45.
Ref 532173Recent Developments in Sterol 14-demethylase Inhibitors for Chagas Disease. Int J Parasitol Drugs Drug Resist. 2012 Dec;2:236-242.
Ref 5326512013 FDA drug approvals. Nat Rev Drug Discov. 2014 Feb;13(2):85-9.
Ref 533086Efinaconazole: Developmental and reproductive toxicity potential of a novel antifungal azole. Reprod Toxicol. 2015 Apr;52:18-25.
Ref 533218Isavuconazonium: first global approval. Drugs. 2015 May;75(7):817-22.
Ref 535752Antifungal agents: mechanisms of action. Trends Microbiol. 2003 Jun;11(6):272-9.
Ref 535932Chemosensitization of fluconazole resistance in Saccharomyces cerevisiae and pathogenic fungi by a D-octapeptide derivative. Antimicrob Agents Chemother. 2004 Apr;48(4):1256-71.
Ref 536031Biological spectra analysis: Linking biological activity profiles to molecular structure. Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):261-6. Epub 2004 Dec 29.
Ref 536273A new, broad-spectrum azole antifungal: posaconazole--mechanisms of action and resistance, spectrum of activity. Mycoses. 2006;49 Suppl 1:2-6.
Ref 536275Antifungal agents: mode of action in yeast cells. Rev Esp Quimioter. 2006 Jun;19(2):130-9.
Ref 536289Investigation of the role of cytochrome P450 2B4 active site residues in substrate metabolism based on crystal structures of the ligand-bound enzyme. Arch Biochem Biophys. 2006 Nov 1;455(1):61-7. Epub 2006 Sep 25.
Ref 536809Differential azole antifungal efficacies contrasted using a Saccharomyces cerevisiae strain humanized for sterol 14 alpha-demethylase at the homologous locus. Antimicrob Agents Chemother. 2008 Oct;52(10):3597-603. Epub 2008 Aug 11.
Ref 537139Sertaconazole: a review of its use in the management of superficial mycoses in dermatology and gynaecology. Drugs. 2009;69(3):339-59. doi: 10.2165/00003495-200969030-00009.
Ref 537454Mode of action of anti-Candida drugs: focus on terconazole and other ergosterol biosynthesis inhibitors. Am J Obstet Gynecol. 1991 Oct;165(4 Pt 2):1193-9.
Ref 537556Clinical pharmacokinetics and pharmacodynamics of solifenacin. Clin Pharmacokinet. 2009;48(5):281-302. doi: 10.2165/00003088-200948050-00001.
Ref 537667Effects of terconazole and other azole antifungal agents on the sterol and carbohydrate composition of Candida albicans. Diagn Microbiol Infect Dis. 1990 Jan-Feb;13(1):31-5.
Ref 537801Bifonazole and clotrimazole. Their mode of action and the possible reason for the fungicidal behaviour of bifonazole. Arzneimittelforschung. 1984;34(2):139-46.
Ref 537803Bifonazole, a biochemist's view. Dermatologica. 1984;169 Suppl 1:3-9.
Ref 549777CS-758. Antifungal lanosterol 14alpha-demethylase inhibitor, 003, vol28, no3, 217-223.
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 556264Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
Ref 1572591Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.

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