Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTY84UG)

• DTT Name: Acetyl-CoA carboxylase 2 (ACACB)
• Synonyms: Acetyl-Coenzyme A carboxylase beta; Acetyl CoA carboxylase beta; ACCbeta; ACC2; ACC-beta; ACACB
• Gene Name: ACACB
• DTT Type: Successful target; [1]
• BioChemical Class: Carbon-carbon ligase
• UniProt ID: ACACB_HUMAN
• TTD ID: T08922
• EC Number: EC 6.4.1.2
• Sequence:
  MVLLLCLSCLIFSCLTFSWLKIWGKMTDSKPITKSKSEANLIPSQEPFPASDNSGETPQR
  NGEGHTLPKTPSQAEPASHKGPKDAGRRRNSLPPSHQKPPRNPLSSSDAAPSPELQANGT
  GTQGLEATDTNGLSSSARPQGQQAGSPSKEDKKQANIKRQLMTNFILGSFDDYSSDEDSV
  AGSSRESTRKGSRASLGALSLEAYLTTGEAETRVPTMRPSMSGLHLVKRGREHKKLDLHR
  DFTVASPAEFVTRFGGDRVIEKVLIANNGIAAVKCMRSIRRWAYEMFRNERAIRFVVMVT
  PEDLKANAEYIKMADHYVPVPGGPNNNNYANVELIVDIAKRIPVQAVWAGWGHASENPKL
  PELLCKNGVAFLGPPSEAMWALGDKIASTVVAQTLQVPTLPWSGSGLTVEWTEDDLQQGK
  RISVPEDVYDKGCVKDVDEGLEAAERIGFPLMIKASEGGGGKGIRKAESAEDFPILFRQV
  QSEIPGSPIFLMKLAQHARHLEVQILADQYGNAVSLFGRDCSIQRRHQKIVEEAPATIAP
  LAIFEFMEQCAIRLAKTVGYVSAGTVEYLYSQDGSFHFLELNPRLQVEHPCTEMIADVNL
  PAAQLQIAMGVPLHRLKDIRLLYGESPWGVTPISFETPSNPPLARGHVIAARITSENPDE
  GFKPSSGTVQELNFRSSKNVWGYFSVAATGGLHEFADSQFGHCFSWGENREEAISNMVVA
  LKELSIRGDFRTTVEYLINLLETESFQNNDIDTGWLDYLIAEKVQAEKPDIMLGVVCGAL
  NVADAMFRTCMTDFLHSLERGQVLPADSLLNLVDVELIYGGVKYILKVARQSLTMFVLIM
  NGCHIEIDAHRLNDGGLLLSYNGNSYTTYMKEEVDSYRITIGNKTCVFEKENDPTVLRSP
  SAGKLTQYTVEDGGHVEAGSSYAEMEVMKMIMTLNVQERGRVKYIKRPGAVLEAGCVVAR
  LELDDPSKVHPAEPFTGELPAQQTLPILGEKLHQVFHSVLENLTNVMSGFCLPEPVFSIK
  LKEWVQKLMMTLRHPSLPLLELQEIMTSVAGRIPAPVEKSVRRVMAQYASNITSVLCQFP
  SQQIATILDCHAATLQRKADREVFFINTQSIVQLVQRYRSGIRGYMKTVVLDLLRRYLRV
  EHHFQQAHYDKCVINLREQFKPDMSQVLDCIFSHAQVAKKNQLVIMLIDELCGPDPSLSD
  ELISILNELTQLSKSEHCKVALRARQILIASHLPSYELRHNQVESIFLSAIDMYGHQFCP
  ENLKKLILSETTIFDVLPTFFYHANKVVCMASLEVYVRRGYIAYELNSLQHRQLPDGTCV
  VEFQFMLPSSHPNRMTVPISITNPDLLRHSTELFMDSGFSPLCQRMGAMVAFRRFEDFTR
  NFDEVISCFANVPKDTPLFSEARTSLYSEDDCKSLREEPIHILNVSIQCADHLEDEALVP
  ILRTFVQSKKNILVDYGLRRITFLIAQEKEFPKFFTFRARDEFAEDRIYRHLEPALAFQL
  ELNRMRNFDLTAVPCANHKMHLYLGAAKVKEGVEVTDHRFFIRAIIRHSDLITKEASFEY
  LQNEGERLLLEAMDELEVAFNNTSVRTDCNHIFLNFVPTVIMDPFKIEESVRYMVMRYGS
  RLWKLRVLQAEVKINIRQTTTGSAVPIRLFITNESGYYLDISLYKEVTDSRSGNIMFHSF
  GNKQGPQHGMLINTPYVTKDLLQAKRFQAQTLGTTYIYDFPEMFRQALFKLWGSPDKYPK
  DILTYTELVLDSQGQLVEMNRLPGGNEVGMVAFKMRFKTQEYPEGRDVIVIGNDITFRIG
  SFGPGEDLLYLRASEMARAEGIPKIYVAANSGARIGMAEEIKHMFHVAWVDPEDPHKGFK
  YLYLTPQDYTRISSLNSVHCKHIEEGGESRYMITDIIGKDDGLGVENLRGSGMIAGESSL
  AYEEIVTISLVTCRAIGIGAYLVRLGQRVIQVENSHIILTGASALNKVLGREVYTSNNQL
  GGVQIMHYNGVSHITVPDDFEGVYTILEWLSYMPKDNHSPVPIITPTDPIDREIEFLPSR
  APYDPRWMLAGRPHPTLKGTWQSGFFDHGSFKEIMAPWAQTVVTGRARLGGIPVGVIAVE
  TRTVEVAVPADPANLDSEAKIIQQAGQVWFPDSAYKTAQAVKDFNREKLPLMIFANWRGF
  SGGMKDMYDQVLKFGAYIVDGLRQYKQPILIYIPPYAELRGGSWVVIDATINPLCIEMYA
  DKESRGGVLEPEGTVEIKFRKKDLIKSMRRIDPAYKKLMEQLGEPDLSDKDRKDLEGRLK
  AREDLLLPIYHQVAVQFADFHDTPGRMLEKGVISDILEWKTARTFLYWRLRRLLLEDQVK
  QEILQASGELSHVHIQSMLRRWFVETEGAVKAYLWDNNQVVVQWLEQHWQAGDGPRSTIR
  ENITYLKHDSVLKTIRGLVEENPEVAVDCVIYLSQHISPAERAQVVHLLSTMDSPAST
• Function: Catalyzes the ATP-dependent carboxylation of acetyl-CoA to malonyl-CoA. Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase. Involved in inhibition of fatty acid and glucose oxidation and enhancement of fat storage. May play a role in regulation of mitochondrial fatty acid oxidation through malonyl- CoA-dependent inhibition of carnitine palmitoyltransferase 1.
• KEGG Pathway:
  Fatty acid biosynthesis (hsa00061)
  Pyruvate metabolism (hsa00620)
  Propanoate metabolism (hsa00640)
  Metabolic pathways (hsa01100)
  Fatty acid metabolism (hsa01212)
  AMPK signaling pathway (hsa04152)
  Insulin signaling pathway (hsa04910)
  Adipocytokine signaling pathway (hsa04920)
  Glucagon signaling pathway (hsa04922)
• Reactome Pathway:
  Import of palmitoyl-CoA into the mitochondrial matrix (R-HSA-200425)
  Activation of gene expression by SREBF (SREBP) (R-HSA-2426168)
  ChREBP activates metabolic gene expression (R-HSA-163765)
• BioCyc Pathway: MetaCyc:HS01211-MON

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metformin	DM89QE1	Colorectal carcinoma		Approved	[1]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PF-05175157	DMLQ3OK	Type-2 diabetes	5A11	Phase 2	[2]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Axokine	DMT5O8I	Obesity	5B81	Discontinued in Phase 3	[3]

6 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-[4-(2,4-Dichlorophenoxy)Phenoxy]Propanoic Acid	DMWXI06	Discovery agent	N.A.	Investigative	[4]
A-80040	DML20N9	Discovery agent	N.A.	Investigative	[5]
AC-8632	DM09BJ4	Parkinson disease	8A00.0	Investigative	[2]
CP-640186	DMO0PS9	Discovery agent	N.A.	Investigative	[6]
QLT-091382	DMWOSFJ	Sebaceous gland disease	EM0Z	Investigative	[2]
Soraphen A	DM18IKZ	Discovery agent	N.A.	Investigative	[7]

References

• [1] AMP-activated protein kinase-dependent and -independent mechanisms underlying in vitro antiglioma action of compound C. Biochem Pharmacol. 2009 Jun 1;77(11):1684-93.
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1264).
• [3] Obesity: pathophysiology and clinical management. Curr Med Chem. 2009;16(4):506-21.
• [4] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [5] Synthesis and structure-activity relationships of N-{3-[2-(4-alkoxyphenoxy)thiazol-5-yl]-1- methylprop-2-ynyl}carboxy derivatives as selective acet... J Med Chem. 2006 Jun 29;49(13):3770-3.
• [6] (4-Piperidinyl)-piperazine: a new platform for acetyl-CoA carboxylase inhibitors. Bioorg Med Chem Lett. 2009 Dec 1;19(23):6645-8.
• [7] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.