Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRL9ZRP)

• DOT Name: ATP-citrate synthase (ACLY)
• Synonyms: EC 2.3.3.8; ATP-citrate (pro-S-)-lyase; ACL; Citrate cleavage enzyme
• Gene Name: ACLY
• UniProt ID: ACLY_HUMAN
• PDB ID: 3MWD ; 3MWE ; 3PFF ; 5TDE ; 5TDF ; 5TDM ; 5TDZ ; 5TE1 ; 5TEQ ; 5TES ; 5TET ; 6HXH ; 6HXK ; 6HXL ; 6HXM ; 6O0H ; 6POE ; 6POF ; 6QFB ; 6UI9 ; 6UIA ; 6UUW ; 6UUZ ; 6UV5 ; 6Z2H ; 7LIW ; 7LJ9 ; 7LLA ; 7RIG ; 7RKZ ; 7RMP ; 8G1E ; 8G1F ; 8G5C ; 8G5D
• EC Number: 2.3.3.8
• Pfam ID: PF16114 ; PF00285 ; PF02629 ; PF00549
• Sequence:
  MSAKAISEQTGKELLYKFICTTSAIQNRFKYARVTPDTDWARLLQDHPWLLSQNLVVKPD
  QLIKRRGKLGLVGVNLTLDGVKSWLKPRLGQEATVGKATGFLKNFLIEPFVPHSQAEEFY
  VCIYATREGDYVLFHHEGGVDVGDVDAKAQKLLVGVDEKLNPEDIKKHLLVHAPEDKKEI
  LASFISGLFNFYEDLYFTYLEINPLVVTKDGVYVLDLAAKVDATADYICKVKWGDIEFPP
  PFGREAYPEEAYIADLDAKSGASLKLTLLNPKGRIWTMVAGGGASVVYSDTICDLGGVNE
  LANYGEYSGAPSEQQTYDYAKTILSLMTREKHPDGKILIIGGSIANFTNVAATFKGIVRA
  IRDYQGPLKEHEVTIFVRRGGPNYQEGLRVMGEVGKTTGIPIHVFGTETHMTAIVGMALG
  HRPIPNQPPTAAHTANFLLNASGSTSTPAPSRTASFSESRADEVAPAKKAKPAMPQDSVP
  SPRSLQGKSTTLFSRHTKAIVWGMQTRAVQGMLDFDYVCSRDEPSVAAMVYPFTGDHKQK
  FYWGHKEILIPVFKNMADAMRKHPEVDVLINFASLRSAYDSTMETMNYAQIRTIAIIAEG
  IPEALTRKLIKKADQKGVTIIGPATVGGIKPGCFKIGNTGGMLDNILASKLYRPGSVAYV
  SRSGGMSNELNNIISRTTDGVYEGVAIGGDRYPGSTFMDHVLRYQDTPGVKMIVVLGEIG
  GTEEYKICRGIKEGRLTKPIVCWCIGTCATMFSSEVQFGHAGACANQASETAVAKNQALK
  EAGVFVPRSFDELGEIIQSVYEDLVANGVIVPAQEVPPPTVPMDYSWARELGLIRKPASF
  MTSICDERGQELIYAGMPITEVFKEEMGIGGVLGLLWFQKRLPKYSCQFIEMCLMVTADH
  GPAVSGAHNTIICARAGKDLVSSLTSGLLTIGDRFGGALDAAAKMFSKAFDSGIIPMEFV
  NKMKKEGKLIMGIGHRVKSINNPDMRVQILKDYVRQHFPATPLLDYALEVEKITTSKKPN
  LILNVDGLIGVAFVDMLRNCGSFTREEADEYIDIGALNGIFVLGRSMGFIGHYLDQKRLK
  QGLYRHPWDDISYVLPEHMSM
• Function: Catalyzes the cleavage of citrate into oxaloacetate and acetyl-CoA, the latter serving as common substrate for de novo cholesterol and fatty acid synthesis.
• KEGG Pathway:
  Citrate cycle (TCA cycle) (hsa00020)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Fatty acyl-CoA biosynthesis (R-HSA-75105)
  ChREBP activates metabolic gene expression (R-HSA-163765)
• BioCyc Pathway: MetaCyc:HS05535-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Lindane	DMB8CNL	Approved	ATP-citrate synthase (ACLY) increases the Lipid metabolism disorders ADR of Lindane.	[27]
Josamycin	DMKJ8LB	Approved	ATP-citrate synthase (ACLY) affects the response to substance of Josamycin.	[28]

31 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 ATP-citrate synthase (ACLY).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of ATP-citrate synthase (ACLY).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of ATP-citrate synthase (ACLY).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of ATP-citrate synthase (ACLY).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ATP-citrate synthase (ACLY).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of ATP-citrate synthase (ACLY).	[6]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of ATP-citrate synthase (ACLY).	[7]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of ATP-citrate synthase (ACLY).	[8]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of ATP-citrate synthase (ACLY).	[9]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of ATP-citrate synthase (ACLY).	[10]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of ATP-citrate synthase (ACLY).	[9]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone increases the expression of ATP-citrate synthase (ACLY).	[11]
OPC-34712	DMHG57U	Approved	OPC-34712 decreases the expression of ATP-citrate synthase (ACLY).	[12]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of ATP-citrate synthase (ACLY).	[13]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of ATP-citrate synthase (ACLY).	[14]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of ATP-citrate synthase (ACLY).	[14]
Guaiacol	DMN4E7T	Phase 3	Guaiacol increases the expression of ATP-citrate synthase (ACLY).	[14]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of ATP-citrate synthase (ACLY).	[14]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of ATP-citrate synthase (ACLY).	[9]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of ATP-citrate synthase (ACLY).	[16]
Puerarin	DMJIMXH	Phase 2	Puerarin increases the expression of ATP-citrate synthase (ACLY).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of ATP-citrate synthase (ACLY).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of ATP-citrate synthase (ACLY).	[20]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of ATP-citrate synthase (ACLY).	[21]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of ATP-citrate synthase (ACLY).	[22]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of ATP-citrate synthase (ACLY).	[23]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of ATP-citrate synthase (ACLY).	[24]
Oleic acid	DM54O1Z	Investigative	Oleic acid decreases the expression of ATP-citrate synthase (ACLY).	[25]
Chlorogenic acid	DM2Y3P4	Investigative	Chlorogenic acid increases the expression of ATP-citrate synthase (ACLY).	[14]
T0901317	DMZQVDI	Investigative	T0901317 increases the expression of ATP-citrate synthase (ACLY).	[1]
Ganoderic acid A	DM42EVG	Investigative	Ganoderic acid A decreases the expression of ATP-citrate synthase (ACLY).	[26]

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 ATP-citrate synthase (ACLY).	[15]

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 increases the methylation of ATP-citrate synthase (ACLY).	[17]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of ATP-citrate synthase (ACLY).	[19]

References

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