beta-secretase 2 | A1: Pepsin | IUPHAR/BPS Guide to PHARMACOLOGY

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beta-secretase 2

Target not currently curated in GtoImmuPdb

Target id: 2331

Nomenclature: beta-secretase 2

Abbreviated Name: BACE2

Family: A1: Pepsin

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

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

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 3 [PMID: 27347366] Hs Inhibition 10.5 pKi 5
pKi 10.5 (Ki 3.1x10-11 M) [5]
verubecestat Hs Inhibition 9.4 pKi 13
pKi 9.4 (Ki 3.7x10-10 M) [13]
compound 3l [PMID: 30637955] Hs Inhibition 8.8 pKi 4
pKi 8.8 (Ki 1.6x10-9 M) [4]
example 41 [WO2012028563] Hs Inhibition 10.0 pIC50 7
pIC50 10.0 (IC50 1x10-10 M) [7]
example 98 [WO2011020806] Hs Inhibition 9.0 pIC50 14
pIC50 9.0 (IC50 1x10-9 M) [14]
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 12
pIC50 8.4 (IC50 4x10-9 M) [12]
NB-360 Hs Inhibition 8.3 pIC50 8
pIC50 8.3 (IC50 5x10-9 M) [8]
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]
AM-6494 Hs Inhibition 7.7 pIC50 11
pIC50 7.7 (IC50 1.86x10-8 M) [11]
RO5508887 Hs Inhibition 7.4 pIC50 6
pIC50 7.4 (IC50 4x10-8 M) [6]
hydroxyethylamine transition-state inhibitor 1 Hs Inhibition 6.2 pIC50 10
pIC50 6.2 (IC50 7x10-7 M) [10]
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0048143 astrocyte activation IEA
General Comments
The diabetes drug target validation status for this enzyme is unclear [9].


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1. Banner D (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, Brindisi M, Yen YC, Lendy EK, Kovela S, Cárdenas EL, Reddy BS, Rao KV, Downs D, Huang X et al.. (2019) Highly Selective and Potent Human β-Secretase 2 (BACE2) Inhibitors against Type 2 Diabetes: Design, Synthesis, X-ray Structure and Structure-Activity Relationship Studies. ChemMedChem, 14 (5): 545-560. [PMID:30637955]

5. 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]

6. 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]

7. 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.

8. 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]

9. 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, DOI: 10.1016/j.jalz.2014.05.733

10. 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]

11. Pettus LH, Bourbeau MP, Bradley J, Bartberger MD, Chen K, Hickman D, Johnson M, Liu Q, Manning JR, Nanez A et al.. (2020) Discovery of AM-6494: A Potent and Orally Efficacious β-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Inhibitor with in Vivo Selectivity over BACE2. J. Med. Chem., 63 (5): 2263-2281. [PMID:31589043]

12. 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.

13. 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.

14. 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-secretase 2. Last modified on 25/10/2019. Accessed on 26/09/2020. IUPHAR/BPS Guide to PHARMACOLOGY,