beta-site APP-cleaving enzyme 2

Target id: 2331

Nomenclature: beta-site APP-cleaving enzyme 2

Abbreviated Name: BACE2

Family: A1: Pepsin

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for beta-site APP-cleaving enzyme 2 in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 518 21q22.3 BACE2 beta-site APP-cleaving enzyme 2
Mouse - 514 16 C4 Bace2 beta-site APP-cleaving enzyme 2
Rat - 514 11q12 Bace2 beta-site APP-cleaving enzyme 2
Previous and Unofficial Names
AEPLC | ALP56 | ARP1 | asp 1 | ASP21 | aspartyl protease 1 | BAE2 | beta-secretase 2 | beta-site amyloid precursor protein cleaving enzyme 2 | CEAP1 | DRAP | memapsin-1 | theta-secretase
Database Links
Specialist databases
MEROPS A01.041 (Hs)
Other databases
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 3.4.23.45

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
compound 3 [PMID: 27347366] Hs Inhibition 10.5 pKi 4
pKi 10.5 (Ki 3.1x10-11 M) [4]
verubecestat Hs Inhibition 9.4 pKi 11
pKi 9.4 (Ki 3.7x10-10 M) [11]
example 41 [WO2012028563] Hs Inhibition 10.0 pIC50 6
pIC50 10.0 (IC50 1x10-10 M) [6]
example 98 [WO2011020806] Hs Inhibition 9.0 pIC50 12
pIC50 9.0 (IC50 1x10-9 M) [12]
example 2 [WO2013004676] Hs Inhibition 8.7 pIC50 2
pIC50 8.7 (IC50 2x10-9 M) [2]
example 92 [WO2012095521] Hs Inhibition 8.4 pIC50 10
pIC50 8.4 (IC50 4x10-9 M) [10]
NB-360 Hs Inhibition 8.3 pIC50 7
pIC50 8.3 (IC50 5x10-9 M) [7]
example 20 [WO2010128058] Hs Inhibition 8.2 pIC50 1
pIC50 8.2 (IC50 6x10-9 M) [1]
Description: Fluorescent-peptide cleavage assay for BACE2 inhibition.
compound J [PMID: 21907142] Hs Inhibition 8.2 pIC50 3
pIC50 8.2 (IC50 6x10-9 M) [3]
RO5508887 Hs Inhibition 7.4 pIC50 5
pIC50 7.4 (IC50 4x10-8 M) [5]
hydroxyethylamine transition-state inhibitor 1 Hs Inhibition 6.2 pIC50 9
pIC50 6.2 (IC50 7x10-7 M) [9]
General Comments
The diabetes drug target validation status for this enzyme is unclear [8].

References

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1. Banner D et.al. (2010) Dihydropyrimidinones for use as BACE2 inhibitors. Patent number: WO2010128058. Assignee: Roche. Priority date: 31/10/2014. Publication date: 11/11/2010.

2. Blass B. (2013) Cyclopropyl-Fused 1,3-Thiazepines as BACE1 and BACE2 Inhibitors. ACS Med Chem Lett, 4 (4): 379-80. [PMID:24900681]

3. Esterházy D, Stützer I, Wang H, Rechsteiner MP, Beauchamp J, Döbeli H, Hilpert H, Matile H, Prummer M, Schmidt A et al.. (2011) Bace2 is a β cell-enriched protease that regulates pancreatic β cell function and mass. Cell Metab., 14 (3): 365-77. [PMID:21907142]

4. Ghosh AK, Reddy BS, Yen YC, Cardenas E, Rao KV, Downs D, Huang X, Tang J, Mesecar AD. (2016) Design of Potent and Highly Selective Inhibitors for Human β-Secretase 2 (Memapsin 1), a Target for Type 2 Diabetes. Chem Sci, 7: 3117-3122. [PMID:27347366]

5. Jacobsen H, Ozmen L, Caruso A, Narquizian R, Hilpert H, Jacobsen B, Terwel D, Tanghe A, Bohrmann B. (2014) Combined treatment with a BACE inhibitor and anti-Aβ antibody gantenerumab enhances amyloid reduction in APPLondon mice. J. Neurosci., 34 (35): 11621-30. [PMID:25164658]

6. Mauser H etal. (2012) Bace inhibitors for use in the treatment of diabetes. Patent number: WO2012028563. Assignee: Roche. Priority date: 01/09/2009. Publication date: 08/03/2012.

7. Neumann U, Rueeger H, Machauer R, Veenstra SJ, Lueoend RM, Tintelnot-Blomley M, Laue G, Beltz K, Vogg B, Schmid P et al.. (2015) A novel BACE inhibitor NB-360 shows a superior pharmacological profile and robust reduction of amyloid-β and neuroinflammation in APP transgenic mice. Mol Neurodegener, 10: 44. [PMID:26336937]

8. O'Donnell P et al. BACE1/2 inhibition does not regulate pancreatic beta cell function and mass in mice. Accessed on 07/08/2015. Modified on 07/08/2015. Alzheimers and Dementia, http://www.alzheimersanddementia.com/article/S1552-5260%2814%2901380-6/fulltext. DOI: 10.1016/j.jalz.2014.05.733

9. Ostermann N, Eder J, Eidhoff U, Zink F, Hassiepen U, Worpenberg S, Maibaum J, Simic O, Hommel U, Gerhartz B. (2006) Crystal structure of human BACE2 in complex with a hydroxyethylamine transition-state inhibitor. J. Mol. Biol., 355 (2): 249-61. [PMID:16305800]

10. Rueeger H et al.. (2012) Bace-2 inhibitors for the treatment of metabolic disorders. Patent number: WO2012095521. Assignee: Novartis. Priority date: 03/01/2011. Publication date: 19/07/2012.

11. Scott JD et al.. (2015) Iminothiadiazine dioxide compounds as BACE inhibitors, compositions, and their use. Patent number: US8940748. Assignee: Merck Sharp & Dohme. Priority date: 08/10/2009. Publication date: 27/01/2015.

12. Southan C. (2013) BACE2 as a new diabetes target: a patent review (2010 - 2012). Expert Opin Ther Pat, 23 (5): 649-63. [PMID:23506624]

How to cite this page

A1: Pepsin: beta-site APP-cleaving enzyme 2. Last modified on 09/05/2018. Accessed on 20/05/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2331.