Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT7AOUD)

• DTT Name: Fatty acid synthase (FASN)
• Synonyms: Yeast fatty acid synthase; Fatty-acyl-CoA synthase; Fatty acyl-CoA synthetase enzyme; FAS
• Gene Name: FASN
• DTT Type: Successful target; [1]
• BioChemical Class: Acyltransferase
• UniProt ID: FAS_HUMAN
• TTD ID: T16514
• EC Number: EC 2.3.1.85
• 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
• 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.
• KEGG Pathway:
  Fatty acid biosynthesis (hsa00061)
  Metabolic pathways (hsa01100)
  Fatty acid metabolism (hsa01212)
  AMPK signaling pathway (hsa04152)
  Insulin signaling pathway (hsa04910)
• Reactome Pathway:
  Activation of gene expression by SREBF (SREBP) (R-HSA-2426168)
  Fatty Acyl-CoA Biosynthesis (R-HSA-75105)
  ChREBP activates metabolic gene expression (R-HSA-163765)
• BioCyc Pathway: MetaCyc:HS09992-MON

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cerulenin	DM6N4PR	Weight loss	MG43.5	Approved	[1]

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Epigallocatechin gallate	DMCGWBJ	Hepatic fibrosis	DB93.0	Phase 3	[2]
TVB-2640	DM19GUH	Astrocytoma	2A00.0Y	Phase 2	[3]

2 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
FAS1	DMAX2EW	Fungal infection	1F29-1F2F	Preclinical	[4]
FSA2	DMLNRCI	Fungal infection	1F29-1F2F	Preclinical	[4]

14 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(-)-CATECHINGALLATE	DMZOGSK	Discovery agent	N.A.	Investigative	[2]
2-Hexadecynoic acid	DMTFIPZ	Discovery agent	N.A.	Investigative	[5]
3,7,3',4'-TETRAHYDROXYFLAVONE	DMES906	Discovery agent	N.A.	Investigative	[2]
4-hydroxy-6-nitro-3-phenylquinolin-2(1H)-one	DMH78QU	Discovery agent	N.A.	Investigative	[6]
4-hydroxy-8-nitro-3-phenylquinolin-2(1H)-one	DMD3OV8	Discovery agent	N.A.	Investigative	[6]
Anti-Fas mabs	DMXWHDC	Solid tumour/cancer	2A00-2F9Z	Investigative	[7]
biochanin A	DM0HPWY	Discovery agent	N.A.	Investigative	[2]
C75	DMHGX1N	Obesity	5B81	Investigative	[8]
FAS-031	DMRMI0V	Solid tumour/cancer	2A00-2F9Z	Investigative	[7]
GALLOCATECHIN GALLATE	DMX2084	Discovery agent	N.A.	Investigative	[2]
GSK2194069	DMZ2TD9	Discovery agent	N.A.	Investigative	[9]
MG-28	DMN1F7Z	Solid tumour/cancer	2A00-2F9Z	Investigative	[7]
MORIN	DM2OGZ5	Discovery agent	N.A.	Investigative	[2]
MT-061	DMDK6BP	Gram-positive bacterial infection	1B74-1G40	Investigative	[7]

References

• [1] Inhibition of fatty acid biosynthesis prevents adipocyte lipotoxicity on human osteoblasts in vitro. J Cell Mol Med. 2010 Apr;14(4):982-91.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] 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).
• [8] 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.
• [9] A human fatty acid synthase inhibitor binds beta-ketoacyl reductase in the keto-substrate site. Nat Chem Biol. 2014 Sep;10(9):774-9.