Protein Information

General Information of the Protein

Protein ID	PT01134
Protein Name	Beta-secretase 2
Secondarily Protein Name	Aspartic-like protease 56 kDa Aspartyl protease 1 Beta-site amyloid precursor protein cleaving enzyme 2 Down region aspartic protease Memapsin-1 Membrane-associated aspartic protease 1 Theta-secretase
Gene Name	BACE2
Secondarily Gene Name	AEPLC ALP56 ASP21 CDA13 UNQ418/PRO852
Sequence	MGALARALLLPLLAQWLLRAAPELAPAPFTLPLRVAAATNRVVAPTPGPGTPAERHADGLALALEPALASPAGAANFLAMVDNLQGDSGRGYYLEMLIGTPPQKLQILVDTGSSNFAVAGTPHSYIDTYFDTERSSTYRSKGFDVTVKYTQGSWTGFVGEDLVTIPKGFNTSFLVNIATIFESENFFLPGIKWNGILGLAYATLAKPSSSLETFFDSLVTQANIPNVFSMQMCGAGLPVAGSGTNGGSLVLGGIEPSLYKGDIWYTPIKEEWYYQIEILKLEIGGQSLNLDCREYNADKAIVDSGTTLLRLPQKVFDAVVEAVARASLIPEFSDGFWTGSQLACWTNSETPWSYFPKISIYLRDENSSRSFRITILPQLYIQPMMGAGLNYECYRFGISPSTNALVIGATVMEGFYVIFDRAQKRVGFAASPCAEIAGAAVSEISGPFSTEDVASNCVPAQSLSEPILWIVSYALMSVCGAILLVLIVLLLLPFRCQRRPRDPEVVNDESSLVRHRWK Show/Hide
Organism	Homo sapiens, Human
Protein Classification	Enzyme > Protease > Aspartic protease > Aspartic protease AA clan > Aspartic protease A1A subfamily
Function	Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves APP, between residues 690 and 691, leading to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase. It has also been shown that it can cleave APP between residues 671 and 672 (PubMed:10591213, PubMed:11083922, PubMed:11423558, PubMed:15857888, PubMed:16816112). Involved in the proteolytic shedding of PMEL at early stages of melanosome biogenesis. Cleaves PMEL within the M-beta fragment to release the amyloidogenic PMEL luminal fragment containing M-alpha and a small portion of M-beta N-terminus. This is a prerequisite step for subsequent processing and assembly of PMEL fibrils into amyloid sheets (PubMed:23754390). Responsible also for the proteolytic processing of CLTRN in pancreatic beta cells (PubMed:21907142). Show/Hide
Uniprot ID	Primary ID: Q9Y5Z0 Secondarily ID: A8K7P1 Q5DIH8 Q8N2D4 Q9H2V8 Q9NZL1 Q9NZL2 Q9UJT6 Show/Hide
Ensembl ID	ENSG00000182240
HGNC ID	HGNC:934
Subcellular Location	Cell membrane Golgi apparatus Endoplasmic reticulum Endosome Melanosome

Map of Molecular Bioactivity Related to the Protein

Map of Molecular Bioactivity Related to the Protein Protein Cell Line Compound Bioactivity Value: <= 0.1 μM > 0.1 μM and <= 10 μM > 10 μM Imprecise Activity

Table of Molecular Bioactivities Related to the Protein

Cell Line ID: CL000011 , CHO

Cell Line Info

Compound ID	Compound Name	Compound Formula
CP0876278 Compound Info	(2R,3S)-3-{[(7-Ethyl-1-methyl-2,2-dioxido-3,4-dihydro-1H-[1,2,5]thiadiazepino[3,4,5-hi]indol-9-yl)carbonyl]amino}-2-hydroxy-4-phenyl-N-{[3-(trifluoromethyl)phenyl]methyl}-1-butanaminium formate Show/Hide	C33H37F3N4O6S	1
1	IC50 = 59 nM Bioactivity Info	TI LI LO TS
CP0943195 Compound Info	N-((2R,3S)-3-{[(7-Ethyl-1-methyl-2,2-dioxido-3,4-dihydro-1H-[1,2,5]thiadiazepino[3,4,5-hi]indol-9-yl)carbonyl]amino}-2-hydroxy-4-phenylbutyl)cyclohexanaminium formate Show/Hide	C31H42N4O6S	1
1	IC50 = 114 nM Bioactivity Info	TI LI LO TS
CP0170144 Compound Info	3-(1,1-dioxo-1,2-thiazinan-2-yl)-5-(ethylamino)-2-fluoro-N-[(2S,3R)-3-hydroxy-1-phenyl-4-({[3-(trifluoromethyl)phenyl]methyl}amino)butan-2-yl]benzamide Show/Hide	C31H36F4N4O4S	1
1	IC50 = 177 nM Bioactivity Info	TI LI LO TS
CP0935597 Compound Info	N-((2R,3S)-3-{[(7-Ethyl-1-methyl-2,2-dioxido-3,4-dihydro-1H-[1,2,5]thiadiazepino[3,4,5-hi]indol-9-yl)carbonyl]amino}-2-hydroxy-4-phenylbutyl)-2,6-dimethyl-2-heptanaminium formate Show/Hide	C34H50N4O6S	1
1	IC50 = 210 nM Bioactivity Info	TI LI LO TS
CP0040694 Compound Info	BMCL193669 Compound 18 Show/Hide	C27H34N4O4S	1
1	IC50 = 263 nM Bioactivity Info	TI LI LO TS
CP0457705 Compound Info	3-(1,1-dioxo-1,2-thiazinan-2-yl)-5-(ethylamino)-N-[(2S,3R)-3-hydroxy-1-phenyl-4-({[3-(trifluoromethoxy)phenyl]methyl}amino)butan-2-yl]benzamide Show/Hide	C31H37F3N4O5S	1
1	IC50 = 600 nM Bioactivity Info	TI LI LO TS
CP0464299 Compound Info	N-[(2S,3R)-1-(3,5-difluorophenyl)-3-hydroxy-4-{[(3-methoxyphenyl)methyl]amino}butan-2-yl]-3-(1,1-dioxo-1,2-thiazinan-2-yl)-5-(ethylamino)benzamide Show/Hide	C31H38F2N4O5S	1
1	IC50 = 630 nM Bioactivity Info	TI LI LO TS
CP0457720 Compound Info	3-(1,1-dioxo-1,2-thiazinan-2-yl)-5-ethoxy-N-[(2S,3R)-3-hydroxy-1-phenyl-4-({[3-(trifluoromethoxy)phenyl]methyl}amino)butan-2-yl]benzamide Show/Hide	C31H36F3N3O6S	1
1	IC50 = 760 nM Bioactivity Info	TI LI LO TS
CP0455072 Compound Info	3-(1,1-dioxo-1,2-thiazinan-2-yl)-5-(ethylamino)-2-fluoro-N-[(2S,3R)-3-hydroxy-4-{[(3-methoxyphenyl)methyl]amino}-1-phenylbutan-2-yl]benzamide Show/Hide	C31H39FN4O5S	1
1	IC50 = 785 nM Bioactivity Info	TI LI LO TS
CP0454070 Compound Info	3-(1,1-dioxo-1,2-thiazinan-2-yl)-5-ethoxy-N-[(2S,3R)-3-hydroxy-1-phenyl-4-({[3-(trifluoromethyl)phenyl]methyl}amino)butan-2-yl]benzamide Show/Hide	C31H36F3N3O5S	1
1	IC50 = 1020 nM Bioactivity Info	TI LI LO TS
CP0489362 Compound Info	3-(2-cyanophenyl)-5-ethoxy-N-[(2S,3R)-3-hydroxy-1-phenyl-4-({[3-(trifluoromethyl)phenyl]methyl}amino)butan-2-yl]benzamide Show/Hide	C34H32F3N3O3	1
1	IC50 = 1050 nM Bioactivity Info	TI LI LO TS
CP0876280 Compound Info	(2R,3S)-3-{[(7-Ethyl-1-methyl-2,2-dioxido-3,4-dihydro-1H-[1,2,5]thiadiazepino[3,4,5-hi]indol-9-yl)carbonyl]amino}-2-hydroxy-N-methyl-4-phenyl-1-butanaminium formate Show/Hide	C26H34N4O6S	1
1	IC50 = 1260 nM Bioactivity Info	TI LI LO TS
CP0230205 Compound Info	3-(1,1-dioxo-1,2-thiazinan-2-yl)-5-(ethylamino)-N-[(2S,3R)-3-hydroxy-1-phenyl-4-({[3-(trifluoromethyl)phenyl]methyl}amino)butan-2-yl]benzamide Show/Hide	C31H37F3N4O4S	1
1	IC50 = 1430 nM Bioactivity Info	TI LI LO TS
CP0935596 Compound Info	(2R,3S)-3-({[3-(1,1-Dioxidotetrahydro-2H-1,2-thiazin-2-yl)-5-(ethylamino)phenyl]carbonyl}amino)-2-hydroxy-4-phenyl-N-{[3-(trifluoromethyl)phenyl]methyl}-1-butanaminium formate Show/Hide	C32H39F3N4O6S	1
1	IC50 = 1430 nM Bioactivity Info	TI LI LO TS
CP0454076 Compound Info	3-(1,1-dioxo-1,2-thiazinan-2-yl)-N-[(2S,3R)-3-hydroxy-1-phenyl-4-({[3-(trifluoromethyl)phenyl]methyl}amino)butan-2-yl]-5-propylbenzamide Show/Hide	C32H38F3N3O4S	1
1	IC50 = 1450 nM Bioactivity Info	TI LI LO TS
CP0489349 Compound Info	3-(1,1-dioxo-1,2-thiazinan-2-yl)-N-[(2S,3R)-3-hydroxy-1-phenyl-4-({[3-(trifluoromethyl)phenyl]methyl}amino)butan-2-yl]-5-(propan-2-ylamino)benzamide Show/Hide	C32H39F3N4O4S	1
1	IC50 = 1660 nM Bioactivity Info	TI LI LO TS
CP0486753 Compound Info	N-[(2S,3R)-4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-3-hydroxy-1-phenylbutan-2-yl]-3-(1,1-dioxo-1,2-thiazinan-2-yl)-5-(ethylamino)benzamide Show/Hide	C32H40N4O4S	1
1	IC50 = 2290 nM Bioactivity Info	TI LI LO TS
CP0455071 Compound Info	3-(1,1-dioxo-1,2-thiazinan-2-yl)-N-[(2S,3R)-4-{[(1-ethyl-1H-pyrazol-4-yl)methyl]amino}-3-hydroxy-1-phenylbutan-2-yl]-5-(ethylamino)-2-fluorobenzamide Show/Hide	C29H39FN6O4S	1
1	IC50 = 2465 nM Bioactivity Info	TI LI LO TS
CP0262731 Compound Info	3-(1,1-dioxo-1,2-thiazinan-2-yl)-5-(ethylamino)-N-[(2S,3R)-3-hydroxy-4-[(6-methoxy-2,3-dihydro-1H-inden-1-yl)amino]-1-phenylbutan-2-yl]benzamide Show/Hide	C33H42N4O5S	1
1	IC50 = 2950 nM Bioactivity Info	TI LI LO TS
CP0897223 Compound Info	N-[(2S,3R)-4-(benzylamino)-3-hydroxy-1-phenylbutan-2-yl]-3-ethyl-9-methyl-10,10-dioxo-10lambda6-thia-1,9-diazatricyclo[6.4.1.04,13]trideca-2,4(13),5,7-tetraene-6-carboxamide;formic acid Show/Hide	C32H38N4O6S	1
1	IC50 = 3020 nM Bioactivity Info	TI LI LO TS
CP0464298 Compound Info	3-(2-acetylphenyl)-5-ethoxy-N-[(2S,3R)-3-hydroxy-1-phenyl-4-({[3-(trifluoromethyl)phenyl]methyl}amino)butan-2-yl]benzamide Show/Hide	C35H35F3N2O4	1
1	IC50 = 3080 nM Bioactivity Info	TI LI LO TS
CP0511437 Compound Info	3-ethoxy-N-[(2S,3R)-3-hydroxy-1-phenyl-4-({[3-(trifluoromethyl)phenyl]methyl}amino)butan-2-yl]-5-(2-methyl-5-oxocyclopent-1-en-1-yl)benzamide Show/Hide	C33H35F3N2O4	1
1	IC50 = 4130 nM Bioactivity Info	TI LI LO TS
CP0454075 Compound Info	3-(1,1-dioxo-1,2-thiazinan-2-yl)-5-(ethylamino)-N-[(2S,3R)-3-hydroxy-4-{[(3-methoxyphenyl)methyl]amino}-1-phenylbutan-2-yl]benzamide Show/Hide	C31H40N4O5S	1
1	IC50 = 4270 nM Bioactivity Info	TI LI LO TS
CP0876281 Compound Info	N-[(2R,3S)-3-({[3-(1,1-Dioxidotetrahydro-2H-1,2-thiazin-2-yl)-5-(ethylamino)phenyl]carbonyl}amino)-2-hydroxy-4-phenylbutyl]-2,6-dimethyl-2-heptanaminium formate Show/Hide	C34H54N4O6S	1
1	IC50 = 4370 nM Bioactivity Info	TI LI LO TS
CP0455080 Compound Info	3-(1,1-dioxo-1,2-thiazolidin-2-yl)-5-ethoxy-N-[(2S,3R)-3-hydroxy-1-phenyl-4-({[3-(trifluoromethyl)phenyl]methyl}amino)butan-2-yl]benzamide Show/Hide	C30H34F3N3O5S	1
1	IC50 = 4680 nM Bioactivity Info	TI LI LO TS
CP0138372 Compound Info	3-(1,1-dioxo-1,2-thiazinan-2-yl)-N-[(2S,3R)-4-{[(1-ethyl-1H-pyrazol-4-yl)methyl]amino}-3-hydroxy-1-phenylbutan-2-yl]-5-(ethylamino)benzamide Show/Hide	C29H40N6O4S	1
1	IC50 = 6920 nM Bioactivity Info	TI LI LO TS
CP0876279 Compound Info	N-[(2R,3S)-3-({[3-(1,1-Dioxidotetrahydro-2H-1,2-thiazin-2-yl)-5-ethylamino)phenyl]carbonyl}amino)-2-hydroxy-4-phenylbutyl]cyclohexanaminiumformate Show/Hide	C30H44N4O6S	1
1	IC50 = 7940 nM Bioactivity Info	TI LI LO TS
CP0454079 Compound Info	3-(1,1-dioxo-1,2-thiazinan-2-yl)-5-(ethylamino)-N-[(2S,3R)-1-(furan-2-yl)-3-hydroxy-4-{[(3-methoxyphenyl)methyl]amino}butan-2-yl]benzamide Show/Hide	C29H38N4O6S	1
1	IC50 = 13215 nM Bioactivity Info	TI LI LO TS
CP0894683 Compound Info	N-[(2R,3S)-3-({[3-(1,1-Dioxidotetrahydro-2H-1,2-thiazin-2-yl)-5-(ethylamino)phenyl]carbonyl}amino)-2-hydroxy-4-phenylbutyl]cyclopropanaminiumformate Show/Hide	C27H38N4O6S	1
1	IC50 = 19500 nM Bioactivity Info	TI LI LO TS
CP0501733 Compound Info	3-ethoxy-N-[(2S,3R)-3-hydroxy-1-phenyl-4-({[3-(trifluoromethyl)phenyl]methyl}amino)butan-2-yl]-5-(2-oxopyrrolidin-1-yl)benzamide Show/Hide	C31H34F3N3O4	1
1	IC50 = 26840 nM Bioactivity Info	TI LI LO TS
CP0454078 Compound Info	BMCL181022 Compound 12 Show/Hide	C30H38N4O4S	1
1	IC50 = 32360 nM Bioactivity Info	TI LI LO TS
CP0897224 Compound Info	(2R,3S)-3-({[3-(1,1-Dioxidotetrahydro-2H-1,2-thiazin-2-yl)-5-(ethylamino)phenyl]carbonyl}amino)-2-hydroxy-4-phenyl-N-(phenylmethyl)-1-butanaminium formate Show/Hide	C31H40N4O6S	1
1	IC50 = 32360 nM Bioactivity Info	TI LI LO TS
CP0880740 Compound Info	(2R,3S)-3-({[3-(1,1-Dioxidotetrahydro-2H-1,2-thiazin-2-yl)-5-(ethylamino)phenyl]carbonyl}amino)-2-hydroxy-N-methyl-4-phenyl-1-butanaminium chloride Show/Hide	C24H35ClN4O4S	1
1	IC50 = 47860 nM Bioactivity Info	TI LI LO TS
CP0464295 Compound Info	3-(1,1-dioxo-1,2-thiazinan-2-yl)-5-(ethylamino)-N-[(2S,3R)-3-hydroxy-4-{[(3-methoxyphenyl)methyl]amino}-1-(1H-pyrazol-1-yl)butan-2-yl]benzamide Show/Hide	C28H38N6O5S	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS
CP0890931 Compound Info	3-(1,1-dioxo-1lambda6-[1,2]thiazinan-2-yl)-5-ethylamino-N-[(1S,2R)-2-hydroxy-1-isopropyl-3-(3-methoxy-benzylamino)-propyl]-benzamide Show/Hide	C27H40N4O5S	1
1	IC50 > 100000 nM Bioactivity Info	TI LI LO TS

Cell Line ID: CL000025 , HEK-293T

Cell Line Info

Cell Line ID: CL000006 , HEK293

Cell Line Info

Cell Line ID: CL000416 , INS-1E

Cell Line Info

Cell Line ID: CL000013 , Sf9

Cell Line Info

Biochemical Assays

Compound ID	Compound Name	Compound Formula
CP0093593 Compound Info	US8940748, 34 Show/Hide	C17H17ClFN5O3S	3
1	Activity = 2.44 nM
2	IC50 = 4.5 nM
3	Ki = 0.22 nM
CP0097529 Compound Info	N-[3-[(4aR,7aS)-2-amino-4a,5,6,7-tetrahydro-4H-cyclopenta[d][1,3]thiazin-7a-yl]-4-fluorophenyl]-5-fluoropyridine-2-carboxamide Show/Hide	C19H18F2N4OS	3
1	Activity = 38.5 nM
2	IC50 = 10.2 nM
3	IC50 = 42.9 nM
CP0124822 Compound Info	US9315520, 7 Show/Hide	C17H18ClN5O2S2	2
1	Activity = 234 nM
2	IC50 = 21.6 nM
CP0097508 Compound Info	US9315520, 45 Show/Hide	C19H21F2N5O3S2	2
1	Activity = 372 nM
2	IC50 = 70.5 nM
CP0097523 Compound Info	US9315520, 1 Show/Hide	C18H19F2N5O3S2	2
1	Activity = 2860 nM
2	IC50 = 238 nM
CP0551183 Compound Info	(4S)-3'-(3,6-dihydro-2H-pyran-5-yl)-1'-fluoro-7'-(2-fluoropyridin-3-yl)spiro[5H-1,3-oxazole-4,5'-chromeno[2,3-c]pyridine]-2-amine Show/Hide	C24H18F2N4O3	1
1	IC50 = 0.8 nM
CP0234609 Compound Info	N-[3-[(1S,5S,6S)-3-amino-1-(difluoromethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4,5-difluorophenyl]-5-prop-2-ynoxypyrazine-2-carboxamide Show/Hide	C21H17F4N5O2S	1
1	IC50 = 9.7 nM
CP0248620 Compound Info	N-[3-[(1S,5S,6S)-3-amino-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4,5-difluorophenyl]-5-prop-2-ynoxypyrazine-2-carboxamide Show/Hide	C22H21F2N5O3S	1
1	IC50 = 18.6 nM
CP0040694 Compound Info	BMCL193669 Compound 18 Show/Hide	C27H34N4O4S	1
1	IC50 = 263 nM
CP0265376 Compound Info	N-[3-[(5R)-3-amino-5-methyl-9-oxa-2-thia-4-azaspiro[5.5]undec-3-en-5-yl]-4-fluorophenyl]-5-(fluoromethoxy)pyrazine-2-carboxamide Show/Hide	C21H23F2N5O3S	1
1	IC50 = 631 nM
CP0230205 Compound Info	3-(1,1-dioxo-1,2-thiazinan-2-yl)-5-(ethylamino)-N-[(2S,3R)-3-hydroxy-1-phenyl-4-({[3-(trifluoromethyl)phenyl]methyl}amino)butan-2-yl]benzamide Show/Hide	C31H37F3N4O4S	2
1	IC50 = 1160 nM
2	IC50 = 4260 nM
CP0075806 Compound Info	N-[3-[(5R)-3-amino-9,9-difluoro-5-methyl-2-thia-4-azaspiro[5.5]undec-3-en-5-yl]-4-fluorophenyl]-5-(fluoromethoxy)pyrazine-2-carboxamide Show/Hide	C22H23F4N5O2S	1
1	IC50 = 1660 nM
CP0198194 Compound Info	N-[3-[(5R)-3-amino-5-methyl-9,9-dioxo-2,9lambda6-dithia-4-azaspiro[5.5]undec-3-en-5-yl]-4-fluorophenyl]-5-(fluoromethoxy)pyrazine-2-carboxamide Show/Hide	C21H23F2N5O4S2	2
1	IC50 = 2090 nM
2	IC50 = 2100 nM
CP0262731 Compound Info	3-(1,1-dioxo-1,2-thiazinan-2-yl)-5-(ethylamino)-N-[(2S,3R)-3-hydroxy-4-[(6-methoxy-2,3-dihydro-1H-inden-1-yl)amino]-1-phenylbutan-2-yl]benzamide Show/Hide	C33H42N4O5S	1
1	IC50 = 2950 nM
CP0069645 Compound Info	1-N-[(2S,3R)-4-(cyclopropylamino)-3-hydroxy-1-phenylbutan-2-yl]-5-(N-methylmethanesulfonamido)-3-N-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide Show/Hide	C31H38N4O5S	1
1	Ki = 240 nM

Clinical Information about the Protein

Target 1 ( Beta-site APP-cleaving enzyme 2 (BACE2) )

Target Type	Clinical trial Target

Similar Protein(s) and Bioactivity Statistics

50% Identity

Protein ID	Protein Name	Protein Organism
PT04397	Beta-secretase 2	Mus musculus, Mouse	Protein Info
PT06225	Beta-secretase 2	Rattus norvegicus, Rat	Protein Info

Cite

About MolBiC

Correspondence

Prof. Feng ZHU

Prof. Leo, Lianyi Han