Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ092ZJ)

• DOT Name: Acetyl-CoA acetyltransferase, cytosolic (ACAT2)
• Synonyms: EC 2.3.1.9; Acetyl-CoA transferase-like protein; Cytosolic acetoacetyl-CoA thiolase
• Gene Name: ACAT2
• Related Disease:
  Lung adenocarcinoma
  Beta-ketothiolase deficiency
  Breast cancer
  Breast carcinoma
  Cholelithiasis
  Coronary atherosclerosis
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Hyperlipidemia
  Obesity
  Prostate neoplasm
  Renal cell carcinoma
  Ulcerative colitis
  Age-related macular degeneration
  Coronary heart disease
  Acetyl-CoA acetyltransferase-2 deficiency
  Amyotrophic lateral sclerosis
  Chronic kidney disease
• UniProt ID: THIC_HUMAN
• PDB ID: 1WL4; 1WL5
• EC Number: 2.3.1.9
• Pfam ID: PF02803 ; PF00108
• Sequence:
  MNAGSDPVVIVSAARTIIGSFNGALAAVPVQDLGSTVIKEVLKRATVAPEDVSEVIFGHV
  LAAGCGQNPVRQASVGAGIPYSVPAWSCQMICGSGLKAVCLAVQSIGIGDSSIVVAGGME
  NMSKAPHLAYLRTGVKIGEMPLTDSILCDGLTDAFHNCHMGITAENVAKKWQVSREDQDK
  VAVLSQNRTENAQKAGHFDKEIVPVLVSTRKGLIEVKTDEFPRHGSNIEAMSKLKPYFLT
  DGTGTVTPANASGINDGAAAVVLMKKSEADKRGLTPLARIVSWSQVGVEPSIMGIGPIPA
  IKQAVTKAGWSLEDVDIFEINEAFAAVSAAIVKELGLNPEKVNIEGGAIALGHPLGASGC
  RILVTLLHTLERMGRSRGVAALCIGGGMGIAMCVQRE
• Function: Involved in the biosynthetic pathway of cholesterol.
• KEGG Pathway:
  Fatty acid degradation (hsa00071)
  Valine, leucine and isoleucine degradation (hsa00280)
  Lysine degradation (hsa00310)
  Tryptophan metabolism (hsa00380)
  Pyruvate metabolism (hsa00620)
  Glyoxylate and dicarboxylate metabolism (hsa00630)
  Butanoate metabolism (hsa00650)
  Terpenoid backbone biosynthesis (hsa00900)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  Fatty acid metabolism (hsa01212)
  Fat digestion and absorption (hsa04975)
• Reactome Pathway: Cholesterol biosynthesis (R-HSA-191273)
• BioCyc Pathway: MetaCyc:ENSG00000120437-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung adenocarcinoma	DISD51WR	Definitive	Biomarker	[1]
Beta-ketothiolase deficiency	DIS7NWEJ	Strong	Genetic Variation	[2]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[3]
Cholelithiasis	DISERLZB	Strong	Altered Expression	[4]
Coronary atherosclerosis	DISKNDYU	Strong	Biomarker	[5]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[7]
Hyperlipidemia	DIS61J3S	Strong	Genetic Variation	[8]
Obesity	DIS47Y1K	Strong	Altered Expression	[3]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[9]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[10]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[11]
Age-related macular degeneration	DIS0XS2C	moderate	Altered Expression	[12]
Coronary heart disease	DIS5OIP1	Disputed	Genetic Variation	[13]
Acetyl-CoA acetyltransferase-2 deficiency	DIS6ITXP	Limited	Autosomal recessive	[14]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[15]
Chronic kidney disease	DISW82R7	Limited	Genetic Variation	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Acetyl-CoA acetyltransferase, cytosolic (ACAT2) affects the response to substance of Topotecan.	[48]
Vinblastine	DM5TVS3	Approved	Acetyl-CoA acetyltransferase, cytosolic (ACAT2) affects the response to substance of Vinblastine.	[48]

33 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 Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[17]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[18]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[19]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[20]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[21]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[22]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[23]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[24]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[25]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[26]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[27]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[28]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[29]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[30]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[31]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[32]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[33]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[34]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[35]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[36]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[37]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[39]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[40]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[41]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[20]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[42]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[43]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[44]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[45]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[24]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[46]
Farnesol	DMV2X1B	Investigative	Farnesol increases the expression of Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[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 Acetyl-CoA acetyltransferase, cytosolic (ACAT2).	[38]

References

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