Target Information

Target General Infomation
Target ID
T16514
Former ID
TTDS00295
Target Name
Fatty acid synthase
Gene Name
FASN
Synonyms
FAS; Fatty acyl-CoA synthetase enzyme; Fatty-acyl-CoA synthase; Yeast fatty acid synthase; FASN
Target Type
Successful
Disease Advanced solid tumor [ICD9: 140-199; ICD10: C00-C75, C7A, C7B]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Dramatic weight loss [ICD9: 783.21; ICD10: R63.4]
Fungal infections [ICD9: 110-118; ICD10: B35-B49]
Gram-positive bacterial infection [ICD9: 001-009, 010-018, 020-027, 030-041, 080-088, 090-099, 100-104]
Mycobacterium tuberculosis infection [ICD10: A15-A19]
Obesity [ICD9: 278; ICD10: E66]
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 and an acyl carrier protein.
BioChemical Class
Acyltransferase
Target Validation
T16514
UniProt ID
P49327
EC Number
EC 3.1.2.14
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
Drugs and Mode of Action
Drug(s) Cerulenin Drug Info Approved Dramatic weight loss [536472]
PA-824 Drug Info Phase 3 Mycobacterium tuberculosis infection [525065]
TVB-2640 Drug Info Phase 1 Advanced solid tumor [524890]
FAS1 Drug Info Preclinical Fungal infections [531492]
FSA2 Drug Info Preclinical Fungal infections [531492]
Inhibitor (-)-CATECHINGALLATE Drug Info [528213]
2-Hexadecynoic acid Drug Info [531170]
4-hydroxy-6-nitro-3-phenylquinolin-2(1H)-one Drug Info [528261]
4-hydroxy-8-nitro-3-phenylquinolin-2(1H)-one Drug Info [528261]
BIOCHANIN Drug Info [528213]
C75 Drug Info [535480]
Cerulenin Drug Info [535387], [537249], [537888]
EPIGALOCATECHIN GALLATE Drug Info [528213]
FAS-031 Drug Info [543659]
FAS1 Drug Info [537364]
FISETIN Drug Info [528213]
FSA2 Drug Info [537364]
GALLOCATECHIN GALLATE Drug Info [528213]
GSK2194069 Drug Info [532905]
MG-28 Drug Info [543659]
MORIN Drug Info [528213]
MT-061 lead Drug Info [543659]
PA-824 Drug Info [536472]
TVB-2640 Drug Info [544409]
Pathways
BioCyc Pathway Fatty acid biosynthesis initiation
Fatty acid elongation -- saturated
Palmitate biosynthesis
KEGG Pathway Fatty acid biosynthesis
Metabolic pathways
Fatty acid metabolism
AMPK signaling pathway
Insulin signaling pathway
Pathway Interaction Database p73 transcription factor network
Validated transcriptional targets of deltaNp63 isoforms
PathWhiz Pathway Fatty Acid Biosynthesis
Reactome ChREBP activates metabolic gene expression
Activation of gene expression by SREBF (SREBP)
Fatty Acyl-CoA Biosynthesis
WikiPathways Fatty Acid Biosynthesis
Nuclear Receptors Meta-Pathway
Liver X Receptor Pathway
Activation of Gene Expression by SREBP (SREBF)
SREBF and miR33 in cholesterol and lipid homeostasis
SREBP signalling
Metabolism of water-soluble vitamins and cofactors
Integration of energy metabolism
Fatty acid, triacylglycerol, and ketone body metabolism
AMPK Signaling
References
Ref 524890ClinicalTrials.gov (NCT02223247) A Phase 1, First-In-Human Study of Escalating Doses of Oral TVB-2640 in Patients With Solid Tumors. U.S. National Institutes of Health.
Ref 525065ClinicalTrials.gov (NCT02342886) Shortening Treatment by Advancing Novel Drugs. U.S. National Institutes of Health.
Ref 531492Identification of a novel cell binding site of periostin involved in tumour growth. Eur J Cancer. 2011 Sep;47(14):2221-9.
Ref 536472Novel agents in the management of Mycobacterium tuberculosis disease. Curr Med Chem. 2007;14(18):2000-8.
Ref 528213J Med Chem. 2006 Jun 1;49(11):3345-53.Inhibition of Plasmodium falciparum fatty acid biosynthesis: evaluation of FabG, FabZ, and FabI as drug targets for flavonoids.
Ref 528261Bioorg Med Chem Lett. 2006 Sep 1;16(17):4620-3. Epub 2006 Jun 19.3-Aryl-4-hydroxyquinolin-2(1H)-one derivatives as type I fatty acid synthase inhibitors.
Ref 531170Bioorg Med Chem. 2010 Nov 1;18(21):7475-85. Epub 2010 Sep 18.2-Hexadecynoic acid inhibits plasmodial FAS-II enzymes and arrests erythrocytic and liver stage Plasmodium infections.
Ref 532905A human fatty acid synthase inhibitor binds beta-ketoacyl reductase in the keto-substrate site. Nat Chem Biol. 2014 Sep;10(9):774-9.
Ref 535387Proliferation 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 535480C75 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. Epub 2002 Jun 11.
Ref 536472Novel agents in the management of Mycobacterium tuberculosis disease. Curr Med Chem. 2007;14(18):2000-8.
Ref 537249Inhibition of Fatty Acid Biosynthesis Prevents Adipocyte Lipotoxicity on Human Osteoblasts In Vitro. J Cell Mol Med. 2009 Mar 27.
Ref 537364Novel 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. Epub 2009 May 7.
Ref 537888The antibiotic cerulenin, a novel tool for biochemistry as an inhibitor of fatty acid synthesis. Bacteriol Rev. 1976 Sep;40(3):681-97.
Ref 543659(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 544409Imidazopyridine-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.

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