Target Information
| Target General Information | Top | |||||
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| Target ID |
T16514
(Former ID: TTDS00295)
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| Target Name |
Fatty acid synthase (FASN)
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| Synonyms |
Yeast fatty acid synthase; Fatty-acyl-CoA synthase; Fatty acyl-CoA synthetase enzyme; FAS
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| Gene Name |
FASN
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | concerning food/fluid intake symptom [ICD-11: MG43] | |||||
| Function |
Fatty acid synthetase catalyzes the formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH. This multifunctional protein has 7 catalytic activities as an acyl carrier protein.
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| BioChemical Class |
Acyltransferase
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| UniProt ID | ||||||
| EC Number |
EC 2.3.1.85
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| Sequence |
MEEVVIAGMSGKLPESENLQEFWDNLIGGVDMVTDDDRRWKAGLYGLPRRSGKLKDLSRF
DASFFGVHPKQAHTMDPQLRLLLEVTYEAIVDGGINPDSLRGTHTGVWVGVSGSETSEAL SRDPETLVGYSMVGCQRAMMANRLSFFFDFRGPSIALDTACSSSLMALQNAYQAIHSGQC PAAIVGGINVLLKPNTSVQFLRLGMLSPEGTCKAFDTAGNGYCRSEGVVAVLLTKKSLAR RVYATILNAGTNTDGFKEQGVTFPSGDIQEQLIRSLYQSAGVAPESFEYIEAHGTGTKVG DPQELNGITRALCATRQEPLLIGSTKSNMGHPEPASGLAALAKVLLSLEHGLWAPNLHFH SPNPEIPALLDGRLQVVDQPLPVRGGNVGINSFGFGGSNVHIILRPNTQPPPAPAPHATL PRLLRASGRTPEAVQKLLEQGLRHSQDLAFLSMLNDIAAVPATAMPFRGYAVLGGERGGP EVQQVPAGERPLWFICSGMGTQWRGMGLSLMRLDRFRDSILRSDEAVKPFGLKVSQLLLS TDESTFDDIVHSFVSLTAIQIGLIDLLSCMGLRPDGIVGHSLGEVACGYADGCLSQEEAV LAAYWRGQCIKEAHLPPGAMAAVGLSWEECKQRCPPGVVPACHNSKDTVTISGPQAPVFE FVEQLRKEGVFAKEVRTGGMAFHSYFMEAIAPPLLQELKKVIREPKPRSARWLSTSIPEA QWHSSLARTSSAEYNVNNLVSPVLFQEALWHVPEHAVVLEIAPHALLQAVLKRGLKPSCT IIPLMKKDHRDNLEFFLAGIGRLHLSGIDANPNALFPPVEFPAPRGTPLISPLIKWDHSL AWDVPAAEDFPNGSGSPSAAIYNIDTSSESPDHYLVDHTLDGRVLFPATGYLSIVWKTLA RALGLGVEQLPVVFEDVVLHQATILPKTGTVSLEVRLLEASRAFEVSENGNLVVSGKVYQ WDDPDPRLFDHPESPTPNPTEPLFLAQAEVYKELRLRGYDYGPHFQGILEASLEGDSGRL LWKDNWVSFMDTMLQMSILGSAKHGLYLPTRVTAIHIDPATHRQKLYTLQDKAQVADVVV SRWLRVTVAGGVHISGLHTESAPRRQQEQQVPILEKFCFTPHTEEGCLSERAALQEELQL CKGLVQALQTKVTQQGLKMVVPGLDGAQIPRDPSQQELPRLLSAACRLQLNGNLQLELAQ VLAQERPKLPEDPLLSGLLDSPALKACLDTAVENMPSLKMKVVEVLAGHGHLYSRIPGLL SPHPLLQLSYTATDRHPQALEAAQAELQQHDVAQGQWDPADPAPSALGSADLLVCNCAVA ALGDPASALSNMVAALREGGFLLLHTLLRGHPLGDIVAFLTSTEPQYGQGILSQDAWESL FSRVSLRLVGLKKSFYGSTLFLCRRPTPQDSPIFLPVDDTSFRWVESLKGILADEDSSRP VWLKAINCATSGVVGLVNCLRREPGGNRLRCVLLSNLSSTSHVPEVDPGSAELQKVLQGD LVMNVYRDGAWGAFRHFLLEEDKPEEPTAHAFVSTLTRGDLSSIRWVCSSLRHAQPTCPG AQLCTVYYASLNFRDIMLATGKLSPDAIPGKWTSQDSLLGMEFSGRDASGKRVMGLVPAK GLATSVLLSPDFLWDVPSNWTLEEAASVPVVYSTAYYALVVRGRVRPGETLLIHSGSGGV GQAAIAIALSLGCRVFTTVGSAEKRAYLQARFPQLDSTSFANSRDTSFEQHVLWHTGGKG VDLVLNSLAEEKLQASVRCLATHGRFLEIGKFDLSQNHPLGMAIFLKNVTFHGVLLDAFF NESSADWREVWALVQAGIRDGVVRPLKCTVFHGAQVEDAFRYMAQGKHIGKVVVQVLAEE PEAVLKGAKPKLMSAISKTFCPAHKSYIIAGGLGGFGLELAQWLIQRGVQKLVLTSRSGI RTGYQAKQVRRWRRQGVQVQVSTSNISSLEGARGLIAEAAQLGPVGGVFNLAVVLRDGLL ENQTPEFFQDVCKPKYSGTLNLDRVTREACPELDYFVVFSSVSCGRGNAGQSNYGFANSA MERICEKRRHEGLPGLAVQWGAIGDVGILVETMSTNDTIVSGTLPQRMASCLEVLDLFLN QPHMVLSSFVLAEKAAAYRDRDSQRDLVEAVAHILGIRDLAAVNLDSSLADLGLDSLMSV EVRQTLERELNLVLSVREVRQLTLRKLQELSSKADEASELACPTPKEDGLAQQQTQLNLR SLLVNPEGPTLMRLNSVQSSERPLFLVHPIEGSTTVFHSLASRLSIPTYGLQCTRAAPLD SIHSLAAYYIDCIRQVQPEGPYRVAGYSYGACVAFEMCSQLQAQQSPAPTHNSLFLFDGS PTYVLAYTQSYRAKLTPGCEAEAETEAICFFVQQFTDMEHNRVLEALLPLKGLEERVAAA VDLIIKSHQGLDRQELSFAARSFYYKLRAAEQYTPKAKYHGNVMLLRAKTGGAYGEDLGA DYNLSQVCDGKVSVHVIEGDHRTLLEGSGLESIISIIHSSLAEPRVSVREG Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| ADReCS ID | BADD_A01285 | |||||
| HIT2.0 ID | T74JJN | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Cerulenin | Drug Info | Approved | Weight loss | [2] | |
| Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
| 1 | Epigallocatechin gallate | Drug Info | Phase 3 | Hepatic fibrosis | [3], [4], [5], [6] | |
| 2 | TVB-2640 | Drug Info | Phase 2 | Astrocytoma | [7], [8] | |
| 3 | TVB-2640 | Drug Info | Phase 2 | Non-alcoholic fatty liver disease | [9] | |
| Preclinical Drug(s) | [+] 2 Preclinical Drugs | + | ||||
| 1 | FAS1 | Drug Info | Preclinical | Fungal infection | [10] | |
| 2 | FSA2 | Drug Info | Preclinical | Fungal infection | [10] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 19 Inhibitor drugs | + | ||||
| 1 | Cerulenin | Drug Info | [1], [11], [12] | |||
| 2 | Epigallocatechin gallate | Drug Info | [13] | |||
| 3 | TVB-2640 | Drug Info | [14] | |||
| 4 | TVB-2640 | Drug Info | [15] | |||
| 5 | FAS1 | Drug Info | [16] | |||
| 6 | FSA2 | Drug Info | [16] | |||
| 7 | (-)-CATECHINGALLATE | Drug Info | [13] | |||
| 8 | 2-Hexadecynoic acid | Drug Info | [17] | |||
| 9 | 3,7,3',4'-TETRAHYDROXYFLAVONE | Drug Info | [13] | |||
| 10 | 4-hydroxy-6-nitro-3-phenylquinolin-2(1H)-one | Drug Info | [18] | |||
| 11 | 4-hydroxy-8-nitro-3-phenylquinolin-2(1H)-one | Drug Info | [18] | |||
| 12 | biochanin A | Drug Info | [13] | |||
| 13 | C75 | Drug Info | [20] | |||
| 14 | FAS-031 | Drug Info | [19] | |||
| 15 | GALLOCATECHIN GALLATE | Drug Info | [13] | |||
| 16 | GSK2194069 | Drug Info | [21] | |||
| 17 | MG-28 | Drug Info | [19] | |||
| 18 | MORIN | Drug Info | [13] | |||
| 19 | MT-061 | Drug Info | [19] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Inhibition of fatty acid biosynthesis prevents adipocyte lipotoxicity on human osteoblasts in vitro. J Cell Mol Med. 2010 Apr;14(4):982-91. | |||||
| REF 2 | Novel agents in the management of Mycobacterium tuberculosis disease. Curr Med Chem. 2007;14(18):2000-8. | |||||
| REF 3 | URL: 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: 7002). | |||||
| REF 4 | The green tea polyphenol (2)-epigallocatechin-3-gallate (EGCG) is not a beta-secretase inhibitor. Bioorg Med Chem Lett. 2012 Feb 1;22(3):1408-14. | |||||
| REF 5 | Epigallocatechin gallate modulates CYP450 isoforms in the female Swiss-Webster mouse. Toxicol Sci. 2003 Dec;76(2):262-70. | |||||
| REF 6 | Prolyl endopeptidase inhibitors from green tea. Arch Pharm Res. 2001 Aug;24(4):292-6. | |||||
| REF 7 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 8 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 9 | ClinicalTrials.gov (NCT03938246) Study of TVB 2640 in Subjects With Non-Alcoholic Steatohepatitis (NASH). U.S. National Institutes of Health. | |||||
| REF 10 | Identification of a novel cell binding site of periostin involved in tumour growth. Eur J Cancer. 2011 Sep;47(14):2221-9. | |||||
| REF 11 | Proliferation inhibition and apoptosis induction of K562 cells by fatty acid synthase inhibitor--cerulenin. Zhonghua Xue Ye Xue Za Zhi. 2000 May;21(5):244-6. | |||||
| REF 12 | The antibiotic cerulenin, a novel tool for biochemistry as an inhibitor of fatty acid synthesis. Bacteriol Rev. 1976 Sep;40(3):681-97. | |||||
| REF 13 | Inhibition of Plasmodium falciparum fatty acid biosynthesis: evaluation of FabG, FabZ, and FabI as drug targets for flavonoids. J Med Chem. 2006 Jun 1;49(11):3345-53. | |||||
| REF 14 | Imidazopyridine-Based Fatty Acid Synthase Inhibitors That Show Anti-HCV Activity and in Vivo Target Modulation. ACS Med Chem Lett. 2013 January 10; 4(1): 113-117. | |||||
| REF 15 | Fatty Acid Synthase Inhibitor TVB-2640 Reduces Hepatic de Novo Lipogenesis in Males With Metabolic Abnormalities. Hepatology. 2020 Jul;72(1):103-118. | |||||
| REF 16 | Novel antifungal agents, targets or therapeutic strategies for the treatment of invasive fungal diseases: a review of the literature (2005-2009). Rev Iberoam Micol. 2009 Mar 31;26(1):15-22. | |||||
| REF 17 | 2-Hexadecynoic acid inhibits plasmodial FAS-II enzymes and arrests erythrocytic and liver stage Plasmodium infections. Bioorg Med Chem. 2010 Nov 1;18(21):7475-85. | |||||
| REF 18 | 3-Aryl-4-hydroxyquinolin-2(1H)-one derivatives as type I fatty acid synthase inhibitors. Bioorg Med Chem Lett. 2006 Sep 1;16(17):4620-3. | |||||
| REF 19 | URL: 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. (Target id: 2608). | |||||
| REF 20 | C75 increases peripheral energy utilization and fatty acid oxidation in diet-induced obesity. Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9498-502. | |||||
| REF 21 | A human fatty acid synthase inhibitor binds beta-ketoacyl reductase in the keto-substrate site. Nat Chem Biol. 2014 Sep;10(9):774-9. | |||||
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