Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUX531P)

• DOT Name: Acyl-CoA 6-desaturase (FADS2)
• Synonyms: EC 1.14.19.3; Delta(6) fatty acid desaturase; D6D; Delta(6) desaturase; Delta-6 desaturase; Fatty acid desaturase 2
• Gene Name: FADS2
• UniProt ID: FADS2_HUMAN
• EC Number: 1.14.19.3
• Pfam ID: PF00173 ; PF00487
• Sequence:
  MGKGGNQGEGAAEREVSVPTFSWEEIQKHNLRTDRWLVIDRKVYNITKWSIQHPGGQRVI
  GHYAGEDATDAFRAFHPDLEFVGKFLKPLLIGELAPEEPSQDHGKNSKITEDFRALRKTA
  EDMNLFKTNHVFFLLLLAHIIALESIAWFTVFYFGNGWIPTLITAFVLATSQAQAGWLQH
  DYGHLSVYRKPKWNHLVHKFVIGHLKGASANWWNHRHFQHHAKPNIFHKDPDVNMLHVFV
  LGEWQPIEYGKKKLKYLPYNHQHEYFFLIGPPLLIPMYFQYQIIMTMIVHKNWVDLAWAV
  SYYIRFFITYIPFYGILGALLFLNFIRFLESHWFVWVTQMNHIVMEIDQEAYRDWFSSQL
  TATCNVEQSFFNDWFSGHLNFQIEHHLFPTMPRHNLHKIAPLVKSLCAKHGIEYQEKPLL
  RALLDIIRSLKKSGKLWLDAYLHK
• Function: Involved in the biosynthesis of highly unsaturated fatty acids (HUFA) from the essential polyunsaturated fatty acids (PUFA) linoleic acid (LA) (18:2n-6) and alpha-linolenic acid (ALA) (18:3n-3) precursors, acting as a fatty acyl-coenzyme A (CoA) desaturase that introduces a cis double bond at carbon 6 of the fatty acyl chain. Catalyzes the first and rate limiting step in this pathway which is the desaturation of LA (18:2n-6) and ALA (18:3n-3) into gamma-linoleate (GLA) (18:3n-6) and stearidonate (18:4n-3), respectively. Subsequently, in the biosynthetic pathway of HUFA n-3 series, it desaturates tetracosapentaenoate (24:5n-3) to tetracosahexaenoate (24:6n-3), which is then converted to docosahexaenoate (DHA)(22:6n-3), an important lipid for nervous system function. Desaturates hexadecanate (palmitate) to produce 6Z-hexadecenoate (sapienate), a fatty acid unique to humans and major component of human sebum, that has been implicated in the development of acne and may have potent antibacterial activity. It can also desaturate (11E)-octadecenoate (trans-vaccenoate, the predominant trans fatty acid in human milk) at carbon 6 generating (6Z,11E)-octadecadienoate. In addition to Delta-6 activity, this enzyme exhibits Delta-8 activity with slight biases toward n-3 fatty acyl-CoA substrates.
• Tissue Specificity: Expressed in a wide array of tissues, highest expression is found in liver followed by brain, lung, heart, and retina. A lower level is found in breast tumor when compared with normal tissues; lowest levels were found in patients with poor prognostic index.
• KEGG Pathway:
  alpha-Linolenic acid metabolism (hsa00592)
  Biosynthesis of unsaturated fatty acids (hsa01040)
  Metabolic pathways (hsa01100)
  Fatty acid metabolism (hsa01212)
  PPAR sig.ling pathway (hsa03320)
• Reactome Pathway:
  alpha-linolenic acid (ALA) metabolism (R-HSA-2046106)
  Linoleic acid (LA) metabolism (R-HSA-2046105)
• BioCyc Pathway: MetaCyc:HS05918-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
Methotrexate	DM2TEOL	Approved	Acyl-CoA 6-desaturase (FADS2) affects the response to substance of Methotrexate.	[29]

31 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 Acyl-CoA 6-desaturase (FADS2).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Acyl-CoA 6-desaturase (FADS2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Acyl-CoA 6-desaturase (FADS2).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Acyl-CoA 6-desaturase (FADS2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Acyl-CoA 6-desaturase (FADS2).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Acyl-CoA 6-desaturase (FADS2).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Acyl-CoA 6-desaturase (FADS2).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine decreases the expression of Acyl-CoA 6-desaturase (FADS2).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Acyl-CoA 6-desaturase (FADS2).	[10]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Acyl-CoA 6-desaturase (FADS2).	[11]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Acyl-CoA 6-desaturase (FADS2).	[12]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Acyl-CoA 6-desaturase (FADS2).	[13]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Acyl-CoA 6-desaturase (FADS2).	[14]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Acyl-CoA 6-desaturase (FADS2).	[15]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of Acyl-CoA 6-desaturase (FADS2).	[16]
Crizotinib	DM4F29C	Approved	Crizotinib increases the expression of Acyl-CoA 6-desaturase (FADS2).	[17]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Acyl-CoA 6-desaturase (FADS2).	[18]
Isoflavone	DM7U58J	Phase 4	Isoflavone increases the expression of Acyl-CoA 6-desaturase (FADS2).	[19]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Acyl-CoA 6-desaturase (FADS2).	[20]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Acyl-CoA 6-desaturase (FADS2).	[9]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Acyl-CoA 6-desaturase (FADS2).	[21]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Acyl-CoA 6-desaturase (FADS2).	[22]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Acyl-CoA 6-desaturase (FADS2).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Acyl-CoA 6-desaturase (FADS2).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Acyl-CoA 6-desaturase (FADS2).	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Acyl-CoA 6-desaturase (FADS2).	[8]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid decreases the expression of Acyl-CoA 6-desaturase (FADS2).	[26]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of Acyl-CoA 6-desaturase (FADS2).	[27]
Chrysin	DM7V2LG	Investigative	Chrysin decreases the expression of Acyl-CoA 6-desaturase (FADS2).	[20]
Linoleic acid	DMDGPY9	Investigative	Linoleic acid increases the expression of Acyl-CoA 6-desaturase (FADS2).	[26]
Ganoderic acid A	DM42EVG	Investigative	Ganoderic acid A decreases the expression of Acyl-CoA 6-desaturase (FADS2).	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the ubiquitination of Acyl-CoA 6-desaturase (FADS2).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Acyl-CoA 6-desaturase (FADS2).	[23]

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