Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3MWER1)

• DOT Name: Fatty acid CoA ligase Acsl3 (ACSL3)
• Synonyms: Arachidonate--CoA ligase; EC 6.2.1.15; Long-chain acyl-CoA synthetase 3; LACS 3; Long-chain-fatty-acid--CoA ligase 3; EC 6.2.1.3; Medium-chain acyl-CoA ligase Acsl3; EC 6.2.1.2
• Gene Name: ACSL3
• Related Disease:
  Advanced cancer
  Brachydactyly
  Castration-resistant prostate carcinoma
  Craniosynostosis
  Glioma
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Hyperlipidemia
  Lung cancer
  Lung carcinoma
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Ptosis
  Syndactyly
  Trichohepatoenteric syndrome
  Asthma
  Epithelial ovarian cancer
  Malignant soft tissue neoplasm
  Melanoma
  Ovarian cancer
  Ovarian neoplasm
  Sarcoma
• UniProt ID: ACSL3_HUMAN
• EC Number: 6.2.1.15; 6.2.1.2; 6.2.1.3
• Pfam ID: PF00501
• Sequence:
  MNNHVSSKPSTMKLKHTINPILLYFIHFLISLYTILTYIPFYFFSESRQEKSNRIKAKPV
  NSKPDSAYRSVNSLDGLASVLYPGCDTLDKVFTYAKNKFKNKRLLGTREVLNEEDEVQPN
  GKIFKKVILGQYNWLSYEDVFVRAFNFGNGLQMLGQKPKTNIAIFCETRAEWMIAAQACF
  MYNFQLVTLYATLGGPAIVHALNETEVTNIITSKELLQTKLKDIVSLVPRLRHIITVDGK
  PPTWSEFPKGIIVHTMAAVEALGAKASMENQPHSKPLPSDIAVIMYTSGSTGLPKGVMIS
  HSNIIAGITGMAERIPELGEEDVYIGYLPLAHVLELSAELVCLSHGCRIGYSSPQTLADQ
  SSKIKKGSKGDTSMLKPTLMAAVPEIMDRIYKNVMNKVSEMSSFQRNLFILAYNYKMEQI
  SKGRNTPLCDSFVFRKVRSLLGGNIRLLLCGGAPLSATTQRFMNICFCCPVGQGYGLTES
  AGAGTISEVWDYNTGRVGAPLVCCEIKLKNWEEGGYFNTDKPHPRGEILIGGQSVTMGYY
  KNEAKTKADFFEDENGQRWLCTGDIGEFEPDGCLKIIDRKKDLVKLQAGEYVSLGKVEAA
  LKNLPLVDNICAYANSYHSYVIGFVVPNQKELTELARKKGLKGTWEELCNSCEMENEVLK
  VLSEAAISASLEKFEIPVKIRLSPEPWTPETGLVTDAFKLKRKELKTHYQADIERMYGRK
• Function: Acyl-CoA synthetases (ACSL) activates long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta-oxidation. Required for the incorporation of fatty acids into phosphatidylcholine, the major phospholipid located on the surface of VLDL (very low density lipoproteins). Has mainly an anabolic role in energy metabolism. Mediates hepatic lipogenesis. Preferentially uses myristate, laurate, arachidonate and eicosapentaenoate as substrates. Both isoforms exhibit the same level of activity.
• 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:HS04703-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Brachydactyly	DIS2533F	Strong	Genetic Variation	[2]
Castration-resistant prostate carcinoma	DISVGAE6	Strong	Biomarker	[3]
Craniosynostosis	DIS6J405	Strong	Genetic Variation	[2]
Glioma	DIS5RPEH	Strong	Genetic Variation	[4]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[5]
Hyperlipidemia	DIS61J3S	Strong	Altered Expression	[6]
Lung cancer	DISCM4YA	Strong	Biomarker	[7]
Lung carcinoma	DISTR26C	Strong	Biomarker	[7]
Prostate cancer	DISF190Y	Strong	Biomarker	[8]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[8]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[9]
Ptosis	DISJZNIY	Strong	Genetic Variation	[2]
Syndactyly	DISZK2BT	Strong	Genetic Variation	[2]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Biomarker	[10]
Asthma	DISW9QNS	moderate	Biomarker	[11]
Epithelial ovarian cancer	DIS56MH2	Limited	Altered Expression	[12]
Malignant soft tissue neoplasm	DISTC6NO	Limited	Biomarker	[13]
Melanoma	DIS1RRCY	Limited	Biomarker	[12]
Ovarian cancer	DISZJHAP	Limited	Altered Expression	[12]
Ovarian neoplasm	DISEAFTY	Limited	Altered Expression	[12]
Sarcoma	DISZDG3U	Limited	Biomarker	[13]

This DOT Affected the Drug Response of 5 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Fatty acid CoA ligase Acsl3 (ACSL3) decreases the response to substance of Cisplatin.	[42]
Etoposide	DMNH3PG	Approved	Fatty acid CoA ligase Acsl3 (ACSL3) affects the response to substance of Etoposide.	[43]
Mitomycin	DMH0ZJE	Approved	Fatty acid CoA ligase Acsl3 (ACSL3) affects the response to substance of Mitomycin.	[43]
Topotecan	DMP6G8T	Approved	Fatty acid CoA ligase Acsl3 (ACSL3) affects the response to substance of Topotecan.	[43]
Mitoxantrone	DMM39BF	Approved	Fatty acid CoA ligase Acsl3 (ACSL3) affects the response to substance of Mitoxantrone.	[43]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[14]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[15]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[16]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[17]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[18]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[19]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[20]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[21]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[22]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[23]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[24]
Capsaicin	DMGMF6V	Approved	Capsaicin decreases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[25]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[26]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[27]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[28]
Isoflavone	DM7U58J	Phase 4	Isoflavone increases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[29]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[30]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[32]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[33]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[35]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[36]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[37]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[38]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[39]
Forskolin	DM6ITNG	Investigative	Forskolin increases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[38]
GW7647	DM9RD0C	Investigative	GW7647 increases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[40]
EPZ-004777	DMLN4V5	Investigative	EPZ-004777 increases the expression of Fatty acid CoA ligase Acsl3 (ACSL3).	[41]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Fatty acid CoA ligase Acsl3 (ACSL3).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Fatty acid CoA ligase Acsl3 (ACSL3).	[34]

References

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