Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTK3C21)

• DTT Name: Acetoacetyl-CoA thiolase (ACAT1)
• Synonyms: T2; MAT; Acetyl-CoA acetyltransferase, mitochondrial
• Gene Name: ACAT1
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Acyltransferase
• UniProt ID: THIL_HUMAN
• TTD ID: T11487
• EC Number: EC 2.3.1.9
• Sequence:
  MAVLAALLRSGARSRSPLLRRLVQEIRYVERSYVSKPTLKEVVIVSATRTPIGSFLGSLS
  LLPATKLGSIAIQGAIEKAGIPKEEVKEAYMGNVLQGGEGQAPTRQAVLGAGLPISTPCT
  TINKVCASGMKAIMMASQSLMCGHQDVMVAGGMESMSNVPYVMNRGSTPYGGVKLEDLIV
  KDGLTDVYNKIHMGSCAENTAKKLNIARNEQDAYAINSYTRSKAAWEAGKFGNEVIPVTV
  TVKGQPDVVVKEDEEYKRVDFSKVPKLKTVFQKENGTVTAANASTLNDGAAALVLMTADA
  AKRLNVTPLARIVAFADAAVEPIDFPIAPVYAASMVLKDVGLKKEDIAMWEVNEAFSLVV
  LANIKMLEIDPQKVNINGGAVSLGHPIGMSGARIVGHLTHALKQGEYGLASICNGGGGAS
  AMLIQKL
• Function: Plays a major role in ketone body metabolism.
• KEGG Pathway:
  Fatty acid degradation (hsa00071)
  Synthesis and degradation of ketone bodies (hsa00072)
  Valine, leucine and isoleucine degradation (hsa00280)
  Lysine degradation (hsa00310)
  Tryptophan metabolism (hsa00380)
  Pyruvate metabolism (hsa00620)
  Glyoxylate and dicarboxylate metabolism (hsa00630)
  Propanoate metabolism (hsa00640)
  Butanoate metabolism (hsa00650)
  Terpenoid backbone biosynthesis (hsa00900)
  Metabolic pathways (hsa01100)
  Biosynthesis of antibiotics (hsa01130)
  Carbon metabolism (hsa01200)
  Fatty acid metabolism (hsa01212)
• Reactome Pathway:
  Utilization of Ketone Bodies (R-HSA-77108)
  Synthesis of Ketone Bodies (R-HSA-77111)
  Branched-chain amino acid catabolism (R-HSA-70895)
• BioCyc Pathway: MetaCyc:HS01167-MON

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ATR-01	DMU67HD	Adrenocortical carcinoma	2D11.Z	Phase 1	[1]

1 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID25470667-Compound-K-604	DMYZ2UA	N. A.	N. A.	Patented	[2]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Benoxaprofen	DM5ZOX8	Inflammation	1A00-CA43.1	Withdrawn from market	[3]

13 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(Z)-2,6-diisopropyl-N-phenyloctadec-9-enamide	DMFLDPU	Discovery agent	N.A.	Investigative	[4]
Nonanoic acid biphenyl-2-ylamide	DM951PF	Discovery agent	N.A.	Investigative	[4]
Octanoic acid biphenyl-2-ylamide	DM4RGCX	Discovery agent	N.A.	Investigative	[4]
PMID16242323C15a	DMM4A7P	Discovery agent	N.A.	Investigative	[5]
PMID16242323C15b	DM7U3RM	Discovery agent	N.A.	Investigative	[5]
PMID16242323C16	DM2Q79X	Discovery agent	N.A.	Investigative	[5]
PMID16242323C18a	DMI5WPQ	Discovery agent	N.A.	Investigative	[5]
PMID16242323C18b	DMIS7NT	Discovery agent	N.A.	Investigative	[5]
PMID16242323C22c	DMFDRMH	Discovery agent	N.A.	Investigative	[5]
PMID16242323C22d	DMJICNL	Discovery agent	N.A.	Investigative	[5]
PMID16242323C26a	DMD0Q7K	Discovery agent	N.A.	Investigative	[5]
PMID16242323C26b	DMF0VLX	Discovery agent	N.A.	Investigative	[5]
PMID16242323C26c	DMT3EU2	Discovery agent	N.A.	Investigative	[5]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Prostate cancer	2C82	Prostate	4.99E-05	0.73	1.46

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Acyltransferase inhibitors: a patent review (2010-present).Expert Opin Ther Pat. 2015 Feb;25(2):145-58.
• [3] Inhibition of lyso-PAF: acetyl-CoA acetyltransferase by salicylates and other compounds. Prostaglandins. 1988 Jun;35(6):939-44.
• [4] Biphenyl versus phenylpyridazine derivatives: the role of the heterocycle in a series of acyl-CoA:cholesterol acyl transferase inhibitors. J Med Chem. 2008 Mar 13;51(5):1474-7.
• [5] Synthesis and biological activity of novel 4-phenyl-1,8-naphthyridin-2(1H)-on-3-yl ureas: potent acyl-CoA:cholesterol acyltransferase inhibitor wit... Bioorg Med Chem Lett. 2006 Jan 1;16(1):44-8.