Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI71MUJ)

• DOT Name: Long-chain-fatty-acid--CoA ligase 4 (ACSL4)
• Synonyms: EC 6.2.1.3; Arachidonate--CoA ligase; EC 6.2.1.15; Long-chain acyl-CoA synthetase 4; LACS 4
• Gene Name: ACSL4
• Related Disease:
  Non-syndromic X-linked intellectual disability
  X-linked intellectual disability
  Adenoma
  Advanced cancer
  Autism
  Chromosomal disorder
  Colon adenocarcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Depression
  Duchenne muscular dystrophy
  Gastric cancer
  Glioma
  Hepatocellular carcinoma
  Intellectual disability, X-linked 63
  Lung adenocarcinoma
  Mental disorder
  Neoplasm
  Neuromuscular disease
  Non-alcoholic fatty liver disease
  Non-alcoholic steatohepatitis
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Stomach cancer
  Systemic lupus erythematosus
  Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome
  Intellectual disability
  Osteoarthritis
  Triple negative breast cancer
  Bipolar disorder
  Leiomyosarcoma
  Lung cancer
  Lung carcinoma
  Malignant soft tissue neoplasm
  Sarcoma
• UniProt ID: ACSL4_HUMAN
• EC Number: 6.2.1.15; 6.2.1.3
• Pfam ID: PF00501
• Sequence:
  MKLKLNVLTIILLPVHLLITIYSALIFIPWYFLTNAKKKNAMAKRIKAKPTSDKPGSPYR
  SVTHFDSLAVIDIPGADTLDKLFDHAVSKFGKKDSLGTREILSEENEMQPNGKVFKKLIL
  GNYKWMNYLEVNRRVNNFGSGLTALGLKPKNTIAIFCETRAEWMIAAQTCFKYNFPLVTL
  YATLGKEAVVHGLNESEASYLITSVELLESKLKTALLDISCVKHIIYVDNKAINKAEYPE
  GFEIHSMQSVEELGSNPENLGIPPSRPTPSDMAIVMYTSGSTGRPKGVMMHHSNLIAGMT
  GQCERIPGLGPKDTYIGYLPLAHVLELTAEISCFTYGCRIGYSSPLTLSDQSSKIKKGSK
  GDCTVLKPTLMAAVPEIMDRIYKNVMSKVQEMNYIQKTLFKIGYDYKLEQIKKGYDAPLC
  NLLLFKKVKALLGGNVRMMLSGGAPLSPQTHRFMNVCFCCPIGQGYGLTESCGAGTVTEV
  TDYTTGRVGAPLICCEIKLKDWQEGGYTINDKPNPRGEIVIGGQNISMGYFKNEEKTAED
  YSVDENGQRWFCTGDIGEFHPDGCLQIIDRKKDLVKLQAGEYVSLGKVEAALKNCPLIDN
  ICAFAKSDQSYVISFVVPNQKRLTLLAQQKGVEGTWVDICNNPAMEAEILKEIREAANAM
  KLERFEIPIKVRLSPEPWTPETGLVTDAFKLKRKELRNHYLKDIERMYGGK
• Function: Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation. Preferentially activates arachidonate and eicosapentaenoate as substrates. Preferentially activates 8,9-EET > 14,15-EET > 5,6-EET > 11,12-EET. Modulates glucose-stimulated insulin secretion by regulating the levels of unesterified EETs. Modulates prostaglandin E2 secretion.
• KEGG Pathway:
  Fatty acid biosynthesis (hsa00061)
  Fatty acid degradation (hsa00071)
  Metabolic pathways (hsa01100)
  Fatty acid metabolism (hsa01212)
  PPAR sig.ling pathway (hsa03320)
  Peroxisome (hsa04146)
  Ferroptosis (hsa04216)
  Thermogenesis (hsa04714)
  Adipocytokine sig.ling pathway (hsa04920)
• Reactome Pathway:
  Synthesis of very long-chain fatty acyl-CoAs (R-HSA-75876)
  Intracellular metabolism of fatty acids regulates insulin secretion (R-HSA-434313)
• BioCyc Pathway: MetaCyc:HS00935-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

37 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-syndromic X-linked intellectual disability	DIS71AI3	Definitive	X-linked	[1]
X-linked intellectual disability	DISYJBY3	Definitive	Genetic Variation	[2]
Adenoma	DIS78ZEV	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Autism	DISV4V1Z	Strong	Genetic Variation	[2]
Chromosomal disorder	DISM5BB5	Strong	Genetic Variation	[5]
Colon adenocarcinoma	DISDRE0J	Strong	Altered Expression	[6]
Colon cancer	DISVC52G	Strong	Biomarker	[3]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[7]
Depression	DIS3XJ69	Strong	Genetic Variation	[8]
Duchenne muscular dystrophy	DISRQ3NV	Strong	Biomarker	[5]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[9]
Glioma	DIS5RPEH	Strong	Altered Expression	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[11]
Intellectual disability, X-linked 63	DISEBC1L	Strong	X-linked	[12]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[13]
Mental disorder	DIS3J5R8	Strong	Biomarker	[14]
Neoplasm	DISZKGEW	Strong	Altered Expression	[15]
Neuromuscular disease	DISQTIJZ	Strong	Biomarker	[5]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[16]
Non-alcoholic steatohepatitis	DIST4788	Strong	Genetic Variation	[16]
Prostate cancer	DISF190Y	Strong	Biomarker	[15]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[15]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[17]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[9]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[18]
Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome	DIS8ORO3	moderate	Biomarker	[19]
Intellectual disability	DISMBNXP	moderate	Biomarker	[20]
Osteoarthritis	DIS05URM	moderate	Biomarker	[21]
Triple negative breast cancer	DISAMG6N	moderate	Altered Expression	[22]
Bipolar disorder	DISAM7J2	Limited	Biomarker	[23]
Leiomyosarcoma	DIS6COXM	Limited	Altered Expression	[24]
Lung cancer	DISCM4YA	Limited	Altered Expression	[25]
Lung carcinoma	DISTR26C	Limited	Altered Expression	[25]
Malignant soft tissue neoplasm	DISTC6NO	Limited	Biomarker	[24]
Sarcoma	DISZDG3U	Limited	Biomarker	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Long-chain-fatty-acid--CoA ligase 4 (ACSL4).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Long-chain-fatty-acid--CoA ligase 4 (ACSL4).	[41]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Long-chain-fatty-acid--CoA ligase 4 (ACSL4).	[27]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Long-chain-fatty-acid--CoA ligase 4 (ACSL4).	[28]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Long-chain-fatty-acid--CoA ligase 4 (ACSL4).	[29]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Long-chain-fatty-acid--CoA ligase 4 (ACSL4).	[30]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Long-chain-fatty-acid--CoA ligase 4 (ACSL4).	[31]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Long-chain-fatty-acid--CoA ligase 4 (ACSL4).	[32]
Triclosan	DMZUR4N	Approved	Triclosan affects the expression of Long-chain-fatty-acid--CoA ligase 4 (ACSL4).	[33]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Long-chain-fatty-acid--CoA ligase 4 (ACSL4).	[34]
Marinol	DM70IK5	Approved	Marinol increases the expression of Long-chain-fatty-acid--CoA ligase 4 (ACSL4).	[35]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of Long-chain-fatty-acid--CoA ligase 4 (ACSL4).	[36]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of Long-chain-fatty-acid--CoA ligase 4 (ACSL4).	[37]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Long-chain-fatty-acid--CoA ligase 4 (ACSL4).	[38]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Long-chain-fatty-acid--CoA ligase 4 (ACSL4).	[39]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Long-chain-fatty-acid--CoA ligase 4 (ACSL4).	[42]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Long-chain-fatty-acid--CoA ligase 4 (ACSL4).	[43]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Long-chain-fatty-acid--CoA ligase 4 (ACSL4).	[44]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Long-chain-fatty-acid--CoA ligase 4 (ACSL4).	[45]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Long-chain-fatty-acid--CoA ligase 4 (ACSL4).	[46]
GW7647	DM9RD0C	Investigative	GW7647 increases the expression of Long-chain-fatty-acid--CoA ligase 4 (ACSL4).	[47]

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 Long-chain-fatty-acid--CoA ligase 4 (ACSL4).	[40]

References

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