Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFII9KG)

• DOT Name: Fatty acid synthase (FASN)
• Synonyms: EC 2.3.1.85; Type I fatty acid synthase) S-acetyltransferase (EC 2.3.1.38); S-malonyltransferase (EC 2.3.1.39); 3-oxoacyl- synthase (EC 2.3.1.41); 3-oxoacyl- reductase (EC 1.1.1.100); 3-hydroxyacyl- dehydratase (EC 4.2.1.59); Enoyl- reductase (EC 1.3.1.39); Acyl- hydrolase (EC 3.1.2.14)]
• Gene Name: FASN
• UniProt ID: FAS_HUMAN
• PDB ID: 1XKT; 2CG5; 2JFD; 2JFK; 2PX6; 3HHD; 3TJM; 4PIV; 4W82; 4W9N; 4Z49; 5C37; 6NNA; 7MHD; 7MHE; 8EYI; 8EYK; 8G7X; 8GKC
• EC Number: 1.1.1.100; 1.3.1.39; 2.3.1.38; 2.3.1.39; 2.3.1.41; 2.3.1.85; 3.1.2.14; 4.2.1.59
• Pfam ID: PF00698 ; PF00107 ; PF21149 ; PF16197 ; PF00109 ; PF02801 ; PF08659 ; PF08242 ; PF21089 ; PF00550 ; PF00975
• 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 is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This multifunctional protein contains 7 catalytic activities and a site for the binding of the prosthetic group 4'-phosphopantetheine of the acyl carrier protein ([ACP]) domain; (Microbial infection) Fatty acid synthetase activity is required for SARS coronavirus-2/SARS-CoV-2 replication.
• Tissue Specificity: Ubiquitous. Prominent expression in brain, lung, liver and mammary gland.
• KEGG Pathway:
  Fatty acid biosynthesis (hsa00061)
  Metabolic pathways (hsa01100)
  Fatty acid metabolism (hsa01212)
  AMPK sig.ling pathway (hsa04152)
  Insulin sig.ling pathway (hsa04910)
  Alcoholic liver disease (hsa04936)
• Reactome Pathway:
  Vitamin B5 (pantothenate) metabolism (R-HSA-199220)
  Activation of gene expression by SREBF (SREBP) (R-HSA-2426168)
  Fatty acyl-CoA biosynthesis (R-HSA-75105)
  NR1H2 & NR1H3 regulate gene expression linked to lipogenesis (R-HSA-9029558)
  ChREBP activates metabolic gene expression (R-HSA-163765)
• BioCyc Pathway: MetaCyc:HS09992-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	Fatty acid synthase (FASN) decreases the response to substance of Mitoxantrone.	[75]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Adenosine triphosphate	DM79F6G	Approved	Fatty acid synthase (FASN) decreases the abundance of Adenosine triphosphate.	[76]

85 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Fatty acid synthase (FASN).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Fatty acid synthase (FASN).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Fatty acid synthase (FASN).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Fatty acid synthase (FASN).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Fatty acid synthase (FASN).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Fatty acid synthase (FASN).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Fatty acid synthase (FASN).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Fatty acid synthase (FASN).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Fatty acid synthase (FASN).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Fatty acid synthase (FASN).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Fatty acid synthase (FASN).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Fatty acid synthase (FASN).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Fatty acid synthase (FASN).	[13]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Fatty acid synthase (FASN).	[14]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Fatty acid synthase (FASN).	[15]
Selenium	DM25CGV	Approved	Selenium increases the expression of Fatty acid synthase (FASN).	[16]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Fatty acid synthase (FASN).	[17]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Fatty acid synthase (FASN).	[3]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Fatty acid synthase (FASN).	[18]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Fatty acid synthase (FASN).	[19]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Fatty acid synthase (FASN).	[20]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Fatty acid synthase (FASN).	[5]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Fatty acid synthase (FASN).	[21]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Fatty acid synthase (FASN).	[22]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Fatty acid synthase (FASN).	[23]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Fatty acid synthase (FASN).	[24]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Fatty acid synthase (FASN).	[25]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Fatty acid synthase (FASN).	[26]
Zidovudine	DM4KI7O	Approved	Zidovudine affects the expression of Fatty acid synthase (FASN).	[27]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Fatty acid synthase (FASN).	[23]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Fatty acid synthase (FASN).	[3]
Ibuprofen	DM8VCBE	Approved	Ibuprofen decreases the expression of Fatty acid synthase (FASN).	[28]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial decreases the expression of Fatty acid synthase (FASN).	[29]
Haloperidol	DM96SE0	Approved	Haloperidol increases the expression of Fatty acid synthase (FASN).	[22]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium decreases the expression of Fatty acid synthase (FASN).	[29]
Lindane	DMB8CNL	Approved	Lindane increases the expression of Fatty acid synthase (FASN).	[30]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid decreases the expression of Fatty acid synthase (FASN).	[31]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone increases the expression of Fatty acid synthase (FASN).	[32]
Lovastatin	DM9OZWQ	Approved	Lovastatin increases the expression of Fatty acid synthase (FASN).	[24]
Glucosamine	DM4ZLFD	Approved	Glucosamine increases the expression of Fatty acid synthase (FASN).	[33]
Orlistat	DMRJSP8	Approved	Orlistat decreases the activity of Fatty acid synthase (FASN).	[34]
Crizotinib	DM4F29C	Approved	Crizotinib increases the expression of Fatty acid synthase (FASN).	[35]
Methimazole	DM25FL8	Approved	Methimazole decreases the expression of Fatty acid synthase (FASN).	[36]
Mitotane	DMU1GX0	Approved	Mitotane decreases the expression of Fatty acid synthase (FASN).	[37]
Nelfinavir mesylate	DMFX6G8	Approved	Nelfinavir mesylate decreases the expression of Fatty acid synthase (FASN).	[38]
Teriflunomide	DMQ2FKJ	Approved	Teriflunomide decreases the expression of Fatty acid synthase (FASN).	[39]
Vitamin B3	DMQVRZH	Approved	Vitamin B3 decreases the expression of Fatty acid synthase (FASN).	[40]
Norethindrone	DMTY169	Approved	Norethindrone increases the activity of Fatty acid synthase (FASN).	[41]
OPC-34712	DMHG57U	Approved	OPC-34712 decreases the expression of Fatty acid synthase (FASN).	[42]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Fatty acid synthase (FASN).	[43]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Fatty acid synthase (FASN).	[44]
Atorvastatin	DMF28YC	Phase 3 Trial	Atorvastatin increases the expression of Fatty acid synthase (FASN).	[24]
Bardoxolone methyl	DMODA2X	Phase 3	Bardoxolone methyl decreases the expression of Fatty acid synthase (FASN).	[45]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Fatty acid synthase (FASN).	[46]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone affects the expression of Fatty acid synthase (FASN).	[47]
Beta-caryophyllene	DM7583A	Phase 2	Beta-caryophyllene decreases the expression of Fatty acid synthase (FASN).	[49]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Fatty acid synthase (FASN).	[50]
LY294002	DMY1AFS	Phase 1	LY294002 decreases the expression of Fatty acid synthase (FASN).	[51]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Fatty acid synthase (FASN).	[52]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Fatty acid synthase (FASN).	[54]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Fatty acid synthase (FASN).	[55]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Fatty acid synthase (FASN).	[56]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Fatty acid synthase (FASN).	[57]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Fatty acid synthase (FASN).	[58]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Fatty acid synthase (FASN).	[15]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Fatty acid synthase (FASN).	[59]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the expression of Fatty acid synthase (FASN).	[60]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Fatty acid synthase (FASN).	[61]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Fatty acid synthase (FASN).	[62]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Fatty acid synthase (FASN).	[63]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl increases the expression of Fatty acid synthase (FASN).	[64]
Dibutyl phthalate	DMEDGKO	Investigative	Dibutyl phthalate increases the expression of Fatty acid synthase (FASN).	[65]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid increases the expression of Fatty acid synthase (FASN).	[3]
Cordycepin	DM72Y01	Investigative	Cordycepin decreases the expression of Fatty acid synthase (FASN).	[66]
Lead acetate	DML0GZ2	Investigative	Lead acetate increases the expression of Fatty acid synthase (FASN).	[67]
GW7647	DM9RD0C	Investigative	GW7647 increases the expression of Fatty acid synthase (FASN).	[68]
GW-3965	DMG60ET	Investigative	GW-3965 increases the expression of Fatty acid synthase (FASN).	[68]
T0901317	DMZQVDI	Investigative	T0901317 decreases the expression of Fatty acid synthase (FASN).	[69]
CITCO	DM0N634	Investigative	CITCO decreases the expression of Fatty acid synthase (FASN).	[39]
NMS-873	DMYKZ6U	Investigative	NMS-873 decreases the expression of Fatty acid synthase (FASN).	[70]
BETULIN	DMGQRON	Investigative	BETULIN decreases the expression of Fatty acid synthase (FASN).	[71]
Ganoderic acid A	DM42EVG	Investigative	Ganoderic acid A decreases the expression of Fatty acid synthase (FASN).	[72]
PF-429242	DMB0OZ3	Investigative	PF-429242 decreases the expression of Fatty acid synthase (FASN).	[71]
paxilline	DMPF2N1	Investigative	paxilline increases the expression of Fatty acid synthase (FASN).	[73]
Raffinose	DMVHDOS	Investigative	Raffinose decreases the expression of Fatty acid synthase (FASN).	[74]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Fatty acid synthase (FASN).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Fatty acid synthase (FASN).	[53]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Fatty acid synthase (FASN).	[48]

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