Therapeutic Targets Database
BIDD Pharmainformatics Databases


TTD Target ID: TTDC00092

Target Information
Type of targetClinical trial target    
Asp 2    
Aspartyl protease 2    
Beta-site APP cleaving enzyme    
Beta-site APP cleaving enzyme 1    
Beta-site AbetaPP-cleaving enzyme    
Beta-site amyloid precursor protein cleaving enzyme    
Beta-site amyloid precursor protein cleaving enzyme 1    
Membrane-associated aspartic protease 2    
Transmembrane aspartic protease    
DiseaseAlzheimer's disease
[ICD9: 331.0   ICD10: G30]
Drug(s)MK-8931Phase II/IIIAlzheimer's disease
CTS-21166Phase I completedAlzheimer's Disease[4]
AZD3293Phase IAlzheimer's disease
E2609Phase IAlzheimer's disease
HPP-854Phase IAlzheimer's disease
RG7129Phase IAlzheimer's disease
(-)-CATECHINGALLATEExperimentalNot Available[5]
(2S)-2'-methoxy kurarinoneExperimentalNot Available[6]
(S)-FLURBIPROFENExperimentalNot Available[7]
4-(2-aminoethyl)-2-cyclohexylphenolExperimentalNot Available[8]
4-(2-aminoethyl)-2-ethylphenolExperimentalNot Available[8]
4-(4-FLUOROBENZYL)PIPERIDINEExperimentalNot Available[8]
6-[2-(1H-INDOL-6-YL)ETHYL]PYRIDIN-2-AMINEExperimentalNot Available[8]
7-PhloroetholExperimentalNot Available[9]
AP-2243ExperimentalNot Available[10]
Carbocyclic PeptidomimeticExperimentalNot Available[11]
DIECKOLExperimentalNot Available[9]
DIOXINODEHYDROECKOLExperimentalNot Available[9]
EckolExperimentalNot Available[9]
GRL-7234ExperimentalNot Available[12]
GSK-188909ExperimentalNot Available[13]
Glu-Leu-Asp-Leu-(CHOH-CH2)-Ala-Ala-Glu-PheExperimentalNot Available[14]
KMI-172ExperimentalNot Available[15]
KMI-494ExperimentalNot Available[15]
KMI-538ExperimentalNot Available[15]
KMI-596ExperimentalNot Available[16]
KURARINONEExperimentalNot Available[6]
KUSHENOL AExperimentalNot Available[6]
LEACHIANONE AExperimentalNot Available[6]
MMI-175ExperimentalNot Available[17]
N-(1-benzylpiperidin-4-yl)-4-sulfanylbutanamideExperimentalNot Available[8]
N~3~-(3-PYRIDIN-3-YLBENZYL)PYRIDINE-2,3-DIAMINEExperimentalNot Available[8]
N~3~-BENZYLPYRIDINE-2,3-DIAMINEExperimentalNot Available[8]
OM00-3ExperimentalNot Available[18]
Oxalyl-DAP derivativeExperimentalNot Available[19]
Oxalyl-DAP derivativeExperimentalNot Available[19]
PHLOROFUCOFUROECKOL AExperimentalNot Available[9]
R-flurbiprofenExperimentalNot Available[7]
TRIPHLOROETHOL AExperimentalNot Available[9]
bis(7)-tacrineExperimentalNot Available[20]
sophoraflavanone GExperimentalNot Available[6]
BioChemical ClassHydrolases acting on peptide bonds (Peptidases)    
EC NumberEC
PathwayAlzheimer's disease
UniProt IDP56817
PDB Structure1FKN; 1M4H; 1PY1; 1SGZ; 1TQF; 1UJJ; 1UJK; 1W50; 1W51; 1XN2; 1XN3; 1XS7; 1YM2; 1YM4; 2B8L; 2B8V; 2F3E; 2F3F; 2FDP; 2G94; 2HIZ; 2HM1; 2IQG; 2IRZ; 2IS0; 2NTR; 2OAH; 2OF0; 2OHK; 2OHL; 2OHM; 2OHN; 2OHP; 2OHQ; 2OHR; 2OHS; 2OHT; 2OHU; 2P4J; 2P83; 2P8H; 2PH6; 2PH8; 2Q11; 2Q15; 2QK5; 2QMD; 2QMF; 2QMG; 2QP8; 2QU2; 2QU3; 2QZK; 2QZL; 2VA5; 2VA6; 2VA7; 2VIE; 2VIJ; 2VIY; 2VIZ; 2VJ6; 2VJ7; 2VJ9; 2VKM; 2VNM; 2VNN; 2WEZ; 2WF0; 2WF1; 2WF2; 2WF3; 2WF4; 2WJO; 2XFI; 2XFJ; 2XFK; 2ZDZ; 2ZE1; 2ZHR; 2ZHS; 2ZHT; 2ZHU; 2ZHV; 2ZJH; 2ZJI; 2ZJJ; 2ZJK; 2ZJL; 2ZJM; 2ZJN; 3BRA; 3BUF; 3BUG; 3BUH; 3CIB; 3CIC; 3CID; 3CKP; 3CKR; 3DM6; 3DUY; 3DV1; 3DV5; 3EXO; 3FKT; 3H0B; 3HVG; 3HW1; 3I25; 3IGB; 3IN3; 3IN4; 3IND; 3INE; 3INF; 3INH; 3IVH; 3IVI; 3IXJ; 3IXK; 3K5C; 3K5D; 3K5F; 3K5G; 3KMX; 3KMY; 3KN0; 3KYR; 3L38; 3L3A; 3L58; 3L59; 3L5B; 3L5C; 3L5D; 3L5E; 3L5F; 3LHG; 3LNK; 3LPI; 3LPJ; 3LPK; 3MSJ; 3MSK; 3MSL; 3N4L; 3NSH; 3OHF; 3OHH; 3OOZ; 3PI5; 3QBH; 3QI1; 3R1G; 3R2F; 3RSV; 3RSX; 3RTH; 3RTM; 3RTN; 3RU1; 3RVI; 3S2O; 3S7L; 3S7M; 3SKF; 3SKG; 3TPJ; 3TPL; 3TPP; 3TPR; 3U6A; 3UDH; 3UDJ; 3UDK; 3UDM; 3UDN; 3UDP; 3UDQ; 3UDR; 3UDY; 3UFL; 3UQP; 3UQR; 3UQU; 3UQW; 3UQX; 3VEU; 3VF3; 3VG1; 3VV6; 3VV7; 3VV8; 3ZMG; 3ZOV; 4ACU; 4ACX; 4AZY; 4B00; 4B05; 4B1C; 4B1D; 4B1E; 4D83; 4D85; 4D88; 4D89; 4D8C; 4DH6; 4DI2; 4DJU; 4DJV; 4DJW; 4DJX; 4DJY; 4DPF; 4DPI; 4DUS; 4DV9; 4DVF; 4EWO; 4EXG; 4FCO; 4FGX; 4FM7; 4FM8; 4FRI; 4FRJ; 4FRK; 4FRS; 4FS4; 4FSE; 4FSL; 4GID; 4H1E; 4H3F; 4H3G; 4H3I; 4H3J; 4HA5; 4HZT; 4I0E; 4I0F; 4I0G; 4I0H; 4I0J; 4I0Z; 4I10; 4I11; 4I12; 4I1C; 4J0T; 4J0V; 4J0Y; 4J0Z; 4J17; 4J1C; 4J1E; 4J1F; 4J1H; 4J1I; 4J1K; 4JOO; 4JP9; 4JPC; 4JPE.    
FunctionResponsible for the proteolytic processing of the amyloid precursor protein (app). Cleaves at the amino terminus of the a-beta peptide sequence, between residues 671 and 672 of app, leads to the generation and extracellular release of beta-cleaved soluble liquid.    
Related US Patent6,326,393
Target ValidationClick to Find Target Validation Information.    
Inhibitor (-)-CATECHINGALLATE[5]
(2S)-2'-methoxy kurarinone[6]
4- (2-aminoethyl)-2-ethylphenol[8]
Carbocyclic Peptidomimetic[11]
Glu-Leu-Asp-Leu- (CHOH-CH2)-Ala-Ala-Glu-Phe[14]
N- (1-benzylpiperidin-4-yl)-4-sulfanylbutanamide[8]
Oxalyl-DAP derivative[19]
Oxalyl-DAP derivative[19]
bis (7)-tacrine[20]
sophoraflavanone G[6]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1A furin-like convertase mediates propeptide cleavage of BACE, the Alzheimer's beta -secretase. J Biol Chem. 2000 Dec 1;275(48):37712-7. To Reference
Ref 2Dehydroepiandrosterone reduces expression and activity of BACE in NT2 neurons exposed to oxidative stress. Neurobiol Dis. 2003 Nov;14(2):291-301. To Reference
Ref 3BACE1 deficiency rescues memory deficits and cholinergic dysfunction in a mouse model of Alzheimer's disease. Neuron. 2004 Jan 8;41(1):27-33. To Reference
Ref 4Safety Study of CTS21166 to Treat Alzheimer Disease. U. S. National Institutes of Health. 2008 To Reference
Ref 5Bioorg Med Chem Lett. 2003 Nov 17;13(22):3905-8.Green tea catechins as a BACE1 (beta-secretase) inhibitor. To Reference
Ref 6Bioorg Med Chem. 2008 Jul 15;16(14):6669-74. Epub 2008 Jun 5.BACE1 inhibitory effects of lavandulyl flavanones from Sophora flavescens. To Reference
Ref 7Bioorg Med Chem Lett. 2006 Apr 15;16(8):2219-23. Epub 2006 Feb 7.The geminal dimethyl analogue of Flurbiprofen as a novel Abeta42 inhibitor and potential Alzheimer's disease modifying agent. To Reference
Ref 8Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. To Reference
Ref 9Bioorg Med Chem Lett. 2010 Jun 1;20(11):3211-5. Epub 2010 Apr 24.Molecular docking studies of phlorotannins from Eisenia bicyclis with BACE1 inhibitory activity. To Reference
Ref 10Bioorg Med Chem Lett. 2008 Jan 1;18(1):423-6. Epub 2007 Oct 4.Multi-target-directed coumarin derivatives: hAChE and BACE1 inhibitors as potential anti-Alzheimer compounds. To Reference
Ref 11J Med Chem. 2005 Aug 11;48(16):5175-90.Structure-based design, synthesis, and memapsin 2 (BACE) inhibitory activity of carbocyclic and heterocyclic peptidomimetics. To Reference
Ref 12J Med Chem. 2007 May 17;50(10):2399-407. Epub 2007 Apr 14.Design, synthesis, and X-ray structure of potent memapsin 2 (beta-secretase) inhibitors with isophthalamide derivatives as the P2-P3-ligands. To Reference
Ref 13Bioorg Med Chem Lett. 2009 Jul 1;19(13):3664-8. Epub 2009 Apr 17.Second generation of BACE-1 inhibitors. Part 1: The need for improved pharmacokinetics. To Reference
Ref 14J Med Chem. 2004 Nov 4;47(23):5791-7.Efficient evaluation of binding free energy using continuum electrostatics solvation. To Reference
Ref 15Bioorg Med Chem Lett. 2007 Mar 15;17(6):1629-33. Epub 2007 Jan 8.Design and synthesis of BACE1 inhibitors containing a novel norstatine derivative (2R,3R)-3-amino-2-hydroxy-4-(phenylthio)butyric acid. To Reference
Ref 16Bioorg Med Chem. 2010 May 1;18(9):3175-86. Epub 2010 Mar 21.Design of pentapeptidic BACE1 inhibitors with carboxylic acid bioisosteres at P1' and P4 positions. To Reference
Ref 17Overington 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 18Bioorg Med Chem. 2007 Jun 15;15(12):4136-43. Epub 2007 Mar 30.Synthesis and biological evaluation of phosphino dipeptide isostere inhibitor of human beta-secretase (BACE1). To Reference
Ref 19Bioorg Med Chem Lett. 2005 Jan 3;15(1):211-5.Design and synthesis of highly active Alzheimer's beta-secretase (BACE1) inhibitors, KMI-420 and KMI-429, with enhanced chemical stability. To Reference
Ref 20J Med Chem. 2009 Sep 10;52(17):5365-79.Pyrano[3,2-c]quinoline-6-chlorotacrine hybrids as a novel family of acetylcholinesterase- and beta-amyloid-directed anti-Alzheimer compounds. To Reference
Ref 21J Med Chem. 2010 Feb 11;53(3):951-65.Discovery of cyclic acylguanidines as highly potent and selective beta-site amyloid cleaving enzyme (BACE) inhibitors: Part I--inhibitor design and validation. To Reference


Welcome to sign our Guestbook.

If you find any error in data or bug in web service, please kindly report it to Dr. Zhu.

Dr. Chen Yuzong
Deputy Director of Center for Computational Science and Engineering
Professor in Department of Pharmacy
National University of Singapore, Singapore

All rights reserved.

Computer-aided Drug Design
about BIDD |  databases |  software |  teaching |  research |  links


Department of Computational Science | National University of Singapore | Blk S17, 3 Science Drive 2, Singapore 117543