Therapeutic Targets Database
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TTD Target ID: TTDC00132

Target Information
NameAkT    
RAC-alpha serine/threonine kinase    
Type of targetClinical trial target    
SynonymsAkt    
C-AKT    
PKB    
Protein kinase B    
RAC-PK-alpha    
Serine/threonine protein kinase PKB    
DiseaseAdvanced, Relapsed/Refractory Multiple Myeloma
[ICD9: 203.0   ICD10: C90.0]
[1][2][3]
Brain ischemic insult
[ICD9: 435, 437   ICD10: G45.9, I67.8]
[4]
Breast cancer
[ICD9: 174, 175   ICD10: C50]
[5]
Cancer, unspecific
[ICD9: 140-229   ICD10: C00-C96]
[6]
Diabetes mellitus
[ICD9: 250   ICD10: E08-E13]
[6]
Glioblastoma Multiforme (GBM)
[ICD9: 191   ICD10: C71]
[7][8][9]
Huntington's disease
[ICD9: 294.1, 333.4   ICD10: F02.2, G10]
[4]
Non-Hodgkin's Lymphoma
[ICD9: 200, 202   ICD10: C82-C85]
[7][8][9]
Non-small Cell Lung Cancer
[ICD9: 162   ICD10: C33, C34]
[7][8][9]
Parkinson's disease
[ICD9: 332   ICD10: F02.3, G20]
[4]
Recurrent Malignant Glioma
[ICD9: 191   ICD10: C71]
[1][2][3]
Refractory, Rare Sarcoma's[1][2][3]
Seizure
[ICD9: 345.9, 780.3   ICD10: G40, P90, R56]
[4]
Solid tumors
[ICD9: 140-199, 210-229   ICD10: C00-C75, C7A, C7B, D10-D36, D3A]
[10]
Stroke
[ICD9: 434.91   ICD10: I61-I63]
[6]
Drug(s)EnzastaurinPhase IIINon Hodgkin Lymphoma[7][11]
RigosertibPhase IIIMyelodysplastic syndromes
2110183Phase IILangerhan cell histiocytosis
2110183Phase IIOvarian cancer
EnzastaurinPhase IIGlioblastoma Multiforme[7][11]
GSK2110183Phase IILeukemia
MK-2206Phase IIColon Cancer; Rectal Cancer[12][13]
MK2206Phase IIColon Cancer; Rectal Cancer[14]
PerifosinePhase IIRefractory Multiple Myeloma, Recurrent Malignant Glioma, Rare Sarcoma's Refractory[1][2][3]
RX-0201Phase IIMetastatic Pancreatic Cancer[10]
GSK2110183Phase I/IIMultiple Myeloma
2110183Phase IMultiple myeloma
AR-12Phase ILymphoma
ARQ 092Phase IInoperable/unresectable late-stage solid tumors
AZD5363Phase ISolid Tumors
AZD5363Phase ISolid tumours
EnzastaurinPhase IBrain and Central Nervous System Tumors[7][11]
GDC-0068Phase ISolid Tumors[15]
GSK2110183Phase IMyeloma
GSK2141795Phase ILymphoma
GSK2141795Phase ISolid Tumors
P70 S6 Kinase/AKT Dual InhibitorPhase ICancer
P70/AKT inhibitorPhase ICancer
RG7440Phase ISolid tumors
TCN-PPhase IAML
VQD-002Phase IHaematological malignancies; leukaemia; non-small-cell lung cancer[14]
ResearchHerpes simplex virus infection
CI-1033Discontinued in Phase IICancer, NSCLC; cancer, colorectal; cancer, head and neck; cancer, thyroid; cancer, breast; cancer, mesothelioma; cancer, sarcoma, general; cancer, melanoma[11]
PerifosineTerminated in Phase IINon-small Cell Lung Cancer[1][2][3]
XL418Suspended in Phase ISolid Tumors[16]
Trametinib + 2141795Cancer
BioChemical ClassTransferases transferring phosphorus-containing groups    
EC NumberEC 2.7.1.-
EC 2.7.1.37
PathwayAcute myeloid leukemia
Adipocytokine signaling pathway
Apoptosis
B cell receptor signaling pathway
Chemokine signaling pathway
Chronic myeloid leukemia
Colorectal cancer
Endometrial cancer
ErbB signaling pathway
Fc epsilon RI signaling pathway
Focal adhesion
Glioma
Insulin signaling pathway
Jak-STAT signaling pathway
MAPK signaling pathway
Melanoma
Non-small cell lung cancer
Pancreatic cancer
Pathways in cancer
Prostate cancer
Renal cell carcinoma
Small cell lung cancer
T cell receptor signaling pathway
Tight junction
Toll-like receptor signaling pathway
VEGF signaling pathway
mTOR signaling pathway
UniProt IDP31749
P31751
Q9Y243
PDB Structure1H10; 1UNP; 1UNQ; 1UNR; 2UVM; 2UZR; 2UZS; 3CQU; 3CQW; 3MV5; 3MVH; 3O96; 3OCB; 3OW4; 3QKK; 3QKL; 3QKM; 4EJN; 4EKK; 4EKL; 4GV1.    
FunctionGeneral protein kinase capable of phosphorylating several known proteins.    
SequenceMSDVAIVKEGWLHKRGEYIKTWRPRYFLLKNDGTFIGYKERPQDVDQREAPLNNFSVAQC QLMKTERPRPNTFIIRCLQWTTVIERTFHVETPEEREEWTTAIQTVADGLKKQEEEEMDF RSGSPSDNSGAEEMEVSLAKPKHRVTMNEFEYLKLLGKGTFGKVILVKEKATGRYYAMKI LKKEVIVAKDEVAHTLTENRVLQNSRHPFLTALKYSFQTHDRLCFVMEYANGGELFFHLS RERVFSEDRARFYGAEIVSALDYLHSEKNVVYRDLKLENLMLDKDGHIKITDFGLCKEGI KDGATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFEL ILMEEIRFPRTLGPEAKSLLSGLLKKDPKQRLGGGSEDAKEIMQHRFFAGIVWQHVYEKK LSPPFKPQVTSETDTRYFDEEFTAQMITITPPDQDDSMECVDSERRPHFPQFSYSASGTA
Related US Patent6,649,640
Target ValidationClick to Find Target Validation Information.    
Inhibitor (Z)-3-[17]
4,5,6,7-tetrabromobenzotriazole[18]
4,5,6-trihydroxy-3-methylphthalide[19]
4-[ (3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol[20]
A-443654,   A-4436554[21]
BISINDOLYLMALEIMIDE IX[22]
BMS-536924[23]
BMS-754807[24]
BX-517[17]
CI-1033[11]
CI-1040,   PD-18435,   PD-184352[22]
Enzastaurin[7][11]
GDC-0068[15]
GF-109203[22]
GSK-690693[25]
GSK690693[26]
Go-6976[22]
Inositol 1,3,4,5-Tetrakisphosphate[27]
KN-62[22]
LY-294002[22]
Lactoquinomycin[26]
MK-2206[12][13]
MK2206[14]
MYRIOCIN[28]
PD-98059[22]
Perifosine[1][2][3]
RO-316233[22]
RX-0201[10]
SB-202190[22]
SB-203580[22]
SB-747651A[25]
STAUROSPORINONE[22]
U-0126[22]
VQD-002[14]
XL418[16]
ZARAGOZIC ACIDS A[28]
MultitargetCI-1033[11]
Enzastaurin[7][11]
XL418[16]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Regulation of mammary stem/progenitor cells by PTEN/Akt/beta-catenin signaling. PLoS Biol. 2009 Jun 2;7(6):e1000121. Epub 2009 Jun 2. To Reference
Ref 2Emerging treatments for multiple myeloma: beyond immunomodulatory drugs and bortezomib. Semin Hematol. 2009 Apr;46(2):166-75. To Reference
Ref 3Akt enzyme: new therapeutic target in cancer and diabetes?. Orv Hetil. 2009 Feb 22;150(8):373-8. To Reference
Ref 4Akt is a molecular target for signal transduction therapy in brain ischemic insult. J Pharmacol Sci. 2003 Aug;92(4):317-27. To Reference
Ref 5Targeting the phosphatidylinositol 3-kinase/Akt pathway for enhancing breast cancer cells to radiotherapy. Mol Cancer Ther. 2003 Apr;2(4):353-60. To Reference
Ref 6PKB/Akt: a key mediator of cell proliferation, survival and insulin responses? J Cell Sci. 2001 Aug;114(Pt 16):2903-10. To Reference
Ref 7Enzastaurin shows preclinical antitumor activity against human transitional cell carcinoma and enhances the activity of gemcitabine. Mol Cancer Ther. 2009 Jul;8(7):1772-8. Epub 2009 Jun 9. To Reference
Ref 8In Vivo Measurements of Tumor Metabolism and Growth after Administration of Enzastaurin Using Small Animal FDG Positron Emission Tomography. J Oncol. 2009;2009:596560. Epub 2009 May 27. To Reference
Ref 9A phase I trial of enzastaurin in patients with recurrent gliomas. Clin Cancer Res. 2009 May 15;15(10):3617-23. Epub 2009 May 5. To Reference
Ref 10CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008. To Reference
Ref 11A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22. To Reference
Ref 12Merck. Product Development Pipeline. July 15 2009. To Reference
Ref 13Merck. Report of Merck. June 04 2009. To Reference
Ref 14Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44. To Reference
Ref 152011 Pipeline of Genentech. To Reference
Ref 16Drug information of XL418. National Cancer Institute. 2009 To Reference
Ref 17Bioorg Med Chem Lett. 2007 Jul 15;17(14):3814-8. Epub 2007 Apr 27.Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 1: design, synthesis and biological activity. To Reference
Ref 18J Med Chem. 2004 Dec 2;47(25):6239-47.Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. To Reference
Ref 19J Nat Prod. 2004 Dec;67(12):2086-9.A phthalide with in vitro growth inhibitory activity from an oidiodendron strain. To Reference
Ref 20J Med Chem. 2006 Nov 2;49(22):6500-9.4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. To Reference
Ref 21J Med Chem. 2007 Jun 28;50(13):2990-3003. Epub 2007 May 25.Syntheses of potent, selective, and orally bioavailable indazole-pyridine series of protein kinase B/Akt inhibitors with reduced hypotension. To Reference
Ref 22Biochem J. 2000 Oct 1;351(Pt 1):95-105.Specificity and mechanism of action of some commonly used protein kinase inhibitors. To Reference
Ref 23J Med Chem. 2005 Sep 8;48(18):5639-43.Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitumor activity. To Reference
Ref 24J Med Chem. 2009 Dec 10;52(23):7360-3.Discovery of a 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitor (BMS-754807) of insulin-like growth factor receptor (IGF-1R) kinase in clinical development. To Reference
Ref 25J Med Chem. 2008 Sep 25;51(18):5663-79.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-ol (GSK690693), a novel inhibitor of AKT kinase. To Reference
Ref 26The PI3K/Akt pathway as a target in the treatment of hematologic malignancies. Anticancer Agents Med Chem. 2009 Jun;9(5):550-9. To Reference
Ref 27Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. To Reference
Ref 28Nat Chem Biol. 2008 Sep;4(9):538-47. Epub 2008 Jul 20.Raft nanodomains contribute to Akt/PKB plasma membrane recruitment and activation. To Reference



 

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Professor in Department of Pharmacy
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