Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTO6SGY)

• DTT Name: AKT3 messenger RNA (AKT3 mRNA)
• Synonyms: STK-2 (mRNA); RAC-PK-gamma (mRNA); Protein kinase B gamma (mRNA); Protein kinase Akt-3 (mRNA); PKBG (mRNA); PKB gamma (mRNA)
• Gene Name: AKT3
• DTT Type: Literature-reported target; [1]
• BioChemical Class: mRNA target
• UniProt ID: AKT3_HUMAN
• TTD ID: T91149
• EC Number: EC 2.7.11.1
• Sequence:
  MSDVTIVKEGWVQKRGEYIKNWRPRYFLLKTDGSFIGYKEKPQDVDLPYPLNNFSVAKCQ
  LMKTERPKPNTFIIRCLQWTTVIERTFHVDTPEEREEWTEAIQAVADRLQRQEEERMNCS
  PTSQIDNIGEEEMDASTTHHKRKTMNDFDYLKLLGKGTFGKVILVREKASGKYYAMKILK
  KEVIIAKDEVAHTLTESRVLKNTRHPFLTSLKYSFQTKDRLCFVMEYVNGGELFFHLSRE
  RVFSEDRTRFYGAEIVSALDYLHSGKIVYRDLKLENLMLDKDGHIKITDFGLCKEGITDA
  ATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILM
  EDIKFPRTLSSDAKSLLSGLLIKDPNKRLGGGPDDAKEIMRHSFFSGVNWQDVYDKKLVP
  PFKPQVTSETDTRYFDEEFTAQTITITPPEKYDEDGMDCMDNERRPHFPQFSYSASGRE
• Function: AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial for the viability of malignant glioma cells. AKT3 isoform may also be the key molecule in up-regulation and down-regulation of MMP13 via IL13. Required for the coordination of mitochondrial biogenesis with growth factor-induced increases in cellular energy demands. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis.
• KEGG Pathway:
  MAPK signaling pathway (hsa04010)
  ErbB signaling pathway (hsa04012)
  Ras signaling pathway (hsa04014)
  Rap1 signaling pathway (hsa04015)
  cGMP-PKG signaling pathway (hsa04022)
  cAMP signaling pathway (hsa04024)
  Chemokine signaling pathway (hsa04062)
  HIF-1 signaling pathway (hsa04066)
  FoxO signaling pathway (hsa04068)
  Sphingolipid signaling pathway (hsa04071)
  mTOR signaling pathway (hsa04150)
  PI3K-Akt signaling pathway (hsa04151)
  AMPK signaling pathway (hsa04152)
  Apoptosis (hsa04210)
  Adrenergic signaling in cardiomyocytes (hsa04261)
  VEGF signaling pathway (hsa04370)
  Osteoclast differentiation (hsa04380)
  Focal adhesion (hsa04510)
  Tight junction (hsa04530)
  Signaling pathways regulating pluripotency of stem cells (hsa04550)
  Platelet activation (hsa04611)
  Toll-like receptor signaling pathway (hsa04620)
  Jak-STAT signaling pathway (hsa04630)
  T cell receptor signaling pathway (hsa04660)
  B cell receptor signaling pathway (hsa04662)
  Fc epsilon RI signaling pathway (hsa04664)
  Fc gamma R-mediated phagocytosis (hsa04666)
  TNF signaling pathway (hsa04668)
  Neurotrophin signaling pathway (hsa04722)
  Cholinergic synapse (hsa04725)
  Dopaminergic synapse (hsa04728)
  Insulin signaling pathway (hsa04910)
  Progesterone-mediated oocyte maturation (hsa04914)
  Estrogen signaling pathway (hsa04915)
  Prolactin signaling pathway (hsa04917)
  Thyroid hormone signaling pathway (hsa04919)
  Adipocytokine signaling pathway (hsa04920)
  Glucagon signaling pathway (hsa04922)
  Regulation of lipolysis in adipocytes (hsa04923)
  Non-alcoholic fatty liver disease (NAFLD) (hsa04932)
  Carbohydrate digestion and absorption (hsa04973)
  Chagas disease (American trypanosomiasis) (hsa05142)
  Toxoplasmosis (hsa05145)
  Tuberculosis (hsa05152)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  Measles (hsa05162)
  Influenza A (hsa05164)
  HTLV-I infection (hsa05166)
  Epstein-Barr virus infection (hsa05169)
  Pathways in cancer (hsa05200)
  Proteoglycans in cancer (hsa05205)
  Colorectal cancer (hsa05210)
  Renal cell carcinoma (hsa05211)
  Pancreatic cancer (hsa05212)
  Endometrial cancer (hsa05213)
  Glioma (hsa05214)
  Prostate cancer (hsa05215)
  Melanoma (hsa05218)
  Chronic myeloid leukemia (hsa05220)
  Acute myeloid leukemia (hsa05221)
  Small cell lung cancer (hsa05222)
  Non-small cell lung cancer (hsa05223)
  Central carbon metabolism in cancer (hsa05230)
  Choline metabolism in cancer (hsa05231)
• Reactome Pathway:
  GPVI-mediated activation cascade (R-HSA-114604)
  PIP3 activates AKT signaling (R-HSA-1257604)
  AKT phosphorylates targets in the cytosol (R-HSA-198323)
  AKT phosphorylates targets in the nucleus (R-HSA-198693)
  Negative regulation of the PI3K/AKT network (R-HSA-199418)
  AKT-mediated inactivation of FOXO1A (R-HSA-211163)
  CD28 dependent PI3K/Akt signaling (R-HSA-389357)
  CTLA4 inhibitory signaling (R-HSA-389513)
  G beta (R-HSA-392451)
  VEGFR2 mediated vascular permeability (R-HSA-5218920)
  TP53 Regulates Metabolic Genes (R-HSA-5628897)
  Constitutive Signaling by AKT1 E17K in Cancer (R-HSA-5674400)
  Activation of BAD and translocation to mitochondria (R-HSA-111447)

Molecular Interaction Atlas (MIA) of This DTT

19 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ISIS 29112	DMECMA6	Discovery agent	N.A.	Investigative	[1]
ISIS 29135	DMGJURC	Discovery agent	N.A.	Investigative	[1]
ISIS 29136	DMAMTLR	Discovery agent	N.A.	Investigative	[1]
ISIS 29137	DMAR1D6	Discovery agent	N.A.	Investigative	[1]
ISIS 29138	DMBY1RS	Discovery agent	N.A.	Investigative	[1]
ISIS 29139	DM2K0RD	Discovery agent	N.A.	Investigative	[1]
ISIS 29154	DMT9F15	Discovery agent	N.A.	Investigative	[1]
ISIS 29155	DMSVN1B	Discovery agent	N.A.	Investigative	[1]
ISIS 29156	DMD8KXB	Discovery agent	N.A.	Investigative	[1]
ISIS 29159	DMLE1IJ	Discovery agent	N.A.	Investigative	[1]
ISIS 29160	DM9NB1A	Discovery agent	N.A.	Investigative	[1]
ISIS 29161	DMPS6OQ	Discovery agent	N.A.	Investigative	[1]
ISIS 29176	DMVLU5J	Discovery agent	N.A.	Investigative	[1]
ISIS 29177	DMSUWVE	Discovery agent	N.A.	Investigative	[1]
ISIS 29178	DMTE7BJ	Discovery agent	N.A.	Investigative	[1]
ISIS 29200	DMN1LHI	Discovery agent	N.A.	Investigative	[1]
ISIS 29201	DMSKVWG	Discovery agent	N.A.	Investigative	[1]
ISIS 29202	DMDR8V9	Discovery agent	N.A.	Investigative	[1]
SB-747651A	DM20Q5O	Discovery agent	N.A.	Investigative	[2]

References

• [1] US patent application no. 6,187,586, Antisense modulation of AKT-3 expression.
• [2] Identification of 4-(2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-{[(3S)-3-piperidinylmethyl]oxy}-1H-imidazo[4,5-c]pyridin-4-yl)-2-methyl-3-butyn-2-o... J Med Chem. 2008 Sep 25;51(18):5663-79.