Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB06ESI)

• DOT Name: Long-chain-fatty-acid--CoA ligase 1 (ACSL1)
• Synonyms: EC 6.2.1.3; Acyl-CoA synthetase 1; ACS1; Arachidonate--CoA ligase; EC 6.2.1.15; Long-chain acyl-CoA synthetase 1; LACS 1; Long-chain acyl-CoA synthetase 2; LACS 2; Long-chain fatty acid-CoA ligase 2; Palmitoyl-CoA ligase 1; Palmitoyl-CoA ligase 2; Phytanate--CoA ligase; EC 6.2.1.24
• Gene Name: ACSL1
• Related Disease:
  Carcinoma
  Acute myocardial infarction
  Cervical Intraepithelial neoplasia
  Colon cancer
  Colon carcinoma
  Glioma
  Glucose metabolism disease
  Hepatocellular carcinoma
  Inflammatory bowel disease
  Neoplasm
  Nephropathy
  Non-alcoholic fatty liver disease
  Obesity
  Type-1/2 diabetes
  Clear cell renal carcinoma
  Colorectal carcinoma
  Undifferentiated carcinoma
  Arteriosclerosis
  Atherosclerosis
  Breast cancer
  Breast carcinoma
  Carcinoma of liver and intrahepatic biliary tract
  Diabetic neuropathy
  Liver cancer
  Lung cancer
  Lung carcinoma
  Non-insulin dependent diabetes
  Type-1 diabetes
  Vascular disease
• UniProt ID: ACSL1_HUMAN
• EC Number: 6.2.1.15; 6.2.1.24; 6.2.1.3
• Pfam ID: PF00501
• Sequence:
  MQAHELFRYFRMPELVDFRQYVRTLPTNTLMGFGAFAALTTFWYATRPKPLKPPCDLSMQ
  SVEVAGSGGARRSALLDSDEPLVYFYDDVTTLYEGFQRGIQVSNNGPCLGSRKPDQPYEW
  LSYKQVAELSECIGSALIQKGFKTAPDQFIGIFAQNRPEWVIIEQGCFAYSMVIVPLYDT
  LGNEAITYIVNKAELSLVFVDKPEKAKLLLEGVENKLIPGLKIIVVMDAYGSELVERGQR
  CGVEVTSMKAMEDLGRANRRKPKPPAPEDLAVICFTSGTTGNPKGAMVTHRNIVSDCSAF
  VKATENTVNPCPDDTLISFLPLAHMFERVVECVMLCHGAKIGFFQGDIRLLMDDLKVLQP
  TVFPVVPRLLNRMFDRIFGQANTTLKRWLLDFASKRKEAELRSGIIRNNSLWDRLIFHKV
  QSSLGGRVRLMVTGAAPVSATVLTFLRAALGCQFYEGYGQTECTAGCCLTMPGDWTAGHV
  GAPMPCNLIKLVDVEEMNYMAAEGEGEVCVKGPNVFQGYLKDPAKTAEALDKDGWLHTGD
  IGKWLPNGTLKIIDRKKHIFKLAQGEYIAPEKIENIYMRSEPVAQVFVHGESLQAFLIAI
  VVPDVETLCSWAQKRGFEGSFEELCRNKDVKKAILEDMVRLGKDSGLKPFEQVKGITLHP
  ELFSIDNGLLTPTMKAKRPELRNYFRSQIDDLYSTIKV
• Function: Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoAs for both synthesis of cellular lipids, and degradation via beta-oxidation. Preferentially uses palmitoleate, oleate and linoleate. Preferentially activates arachidonate than epoxyeicosatrienoic acids (EETs) or hydroxyeicosatrienoic acids (HETEs).
• Tissue Specificity: Highly expressed in liver, heart, skeletal muscle, kidney and erythroid cells, and to a lesser extent in brain, lung, placenta and pancreas.
• 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:
  Linoleic acid (LA) metabolism (R-HSA-2046105)
  alpha-linolenic acid (ALA) metabolism (R-HSA-2046106)
  Synthesis of very long-chain fatty acyl-CoAs (R-HSA-75876)
  PPARA activates gene expression (R-HSA-1989781)
• BioCyc Pathway: MetaCyc:HS07766-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Definitive	Biomarker	[1]
Acute myocardial infarction	DISE3HTG	Strong	Altered Expression	[2]
Cervical Intraepithelial neoplasia	DISXP757	Strong	Genetic Variation	[3]
Colon cancer	DISVC52G	Strong	Genetic Variation	[4]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[4]
Glioma	DIS5RPEH	Strong	Biomarker	[5]
Glucose metabolism disease	DIS5IK09	Strong	Biomarker	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[7]
Inflammatory bowel disease	DISGN23E	Strong	Altered Expression	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[9]
Nephropathy	DISXWP4P	Strong	Altered Expression	[10]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Altered Expression	[11]
Obesity	DIS47Y1K	Strong	Altered Expression	[12]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[13]
Clear cell renal carcinoma	DISBXRFJ	moderate	Altered Expression	[9]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[14]
Undifferentiated carcinoma	DISIAZST	Disputed	Biomarker	[1]
Arteriosclerosis	DISK5QGC	Limited	Altered Expression	[2]
Atherosclerosis	DISMN9J3	Limited	Altered Expression	[2]
Breast cancer	DIS7DPX1	Limited	Biomarker	[15]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[15]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Biomarker	[16]
Diabetic neuropathy	DISX6VF8	Limited	Altered Expression	[17]
Liver cancer	DISDE4BI	Limited	Biomarker	[16]
Lung cancer	DISCM4YA	Limited	Altered Expression	[18]
Lung carcinoma	DISTR26C	Limited	Altered Expression	[18]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[19]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[20]
Vascular disease	DISVS67S	Limited	Biomarker	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitomycin	DMH0ZJE	Approved	Long-chain-fatty-acid--CoA ligase 1 (ACSL1) affects the response to substance of Mitomycin.	[51]

37 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 Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[21]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[22]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[23]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[24]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[25]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[26]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[27]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[28]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[29]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[30]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[31]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[32]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[33]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[27]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[34]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[31]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[35]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[37]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[38]
Nicotine	DMWX5CO	Approved	Nicotine increases the splicing of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[39]
Cidofovir	DMA13GD	Approved	Cidofovir decreases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[27]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[40]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[41]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[27]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[27]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[27]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[42]
Prednisolone	DMQ8FR2	Approved	Prednisolone increases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[43]
Bezafibrate	DMZDCS0	Approved	Bezafibrate increases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[44]
Tolcapone	DM8MNVO	Approved	Tolcapone decreases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[45]
Promegestone	DMK4S8I	Approved	Promegestone increases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[46]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[35]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[48]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[49]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[50]
Linalool	DMGZQ5P	Investigative	Linalool increases the expression of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[41]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[36]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Long-chain-fatty-acid--CoA ligase 1 (ACSL1).	[36]

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 1 (ACSL1).	[47]

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