Page last updated: 2024-08-07 16:52:28
Beta-secretase 1
A beta-secretase 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P56817]
Synonyms
EC 3.4.23.46;
Aspartyl protease 2;
ASP2;
Asp 2;
Beta-site amyloid precursor protein cleaving enzyme 1;
Beta-site APP cleaving enzyme 1;
Memapsin-2;
Membrane-associated aspartic protease 2
Research
Bioassay Publications (111)
| Timeframe | Studies on this Protein(%) | All Drugs % |
|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 35 (31.53) | 29.6817 |
| 2010's | 69 (62.16) | 24.3611 |
| 2020's | 7 (6.31) | 2.80 |
Compounds (118)
Drugs with Inhibition Measurements
| Drug | Taxonomy | Measurement | Average (mM) | Bioassay(s) | Publication(s) |
|---|
| coumarin | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| phloroglucinol | Homo sapiens (human) | IC50 | 36.4700 | 1 | 1 |
| 5-methoxypsoralen | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| chloroquine | Homo sapiens (human) | IC50 | 9.8500 | 2 | 2 |
| donepezil | Homo sapiens (human) | IC50 | 0.8666 | 5 | 5 |
| p-hydroxyamphetamine | Homo sapiens (human) | IC50 | 100.0000 | 1 | 1 |
| methoxsalen | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| ficusin | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| scoparone | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| catechin | Homo sapiens (human) | IC50 | 35.0000 | 1 | 1 |
| 9-(2,3-dihydroxy-3-methylbutoxy)-4-methoxy-7h-furo(3,2-g)(1)benzopyran-7-one | Homo sapiens (human) | IC50 | 219.7000 | 1 | 1 |
| 9-(2,3-dihydroxy-3-methylbutoxy)-4-methoxy-7h-furo(3,2-g)(1)benzopyran-7-one | Homo sapiens (human) | Ki | 30.6000 | 2 | 2 |
| imperatorin | Homo sapiens (human) | IC50 | 61.1500 | 2 | 2 |
| osthol | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| ninhydrin | Homo sapiens (human) | IC50 | 776.0000 | 1 | 1 |
| angelicin | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| herniarin | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| 1,2-Dihydroquinolin-2-imine | Homo sapiens (human) | IC50 | 1,600.0000 | 3 | 3 |
| aviprin | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| oxypeucadanin, (s)-(-)-isomer | Homo sapiens (human) | IC50 | 359.2000 | 1 | 1 |
| epigallocatechin gallate | Homo sapiens (human) | IC50 | 1.1785 | 2 | 2 |
| gallocatechol | Homo sapiens (human) | IC50 | 2.5000 | 1 | 1 |
| xanthotoxol | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| xanthyletine | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| 1,2,3,4,6-pentakis-O-galloyl-beta-D-glucose | Homo sapiens (human) | IC50 | 3.7600 | 1 | 1 |
| 1,2,3,4,6-pentakis-O-galloyl-beta-D-glucose | Homo sapiens (human) | Ki | 5.1300 | 1 | 1 |
| isopimpinellin | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| isoimperatorin | Homo sapiens (human) | IC50 | 244.2000 | 2 | 2 |
| seselin | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| suberosin | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| vexibinol | Homo sapiens (human) | IC50 | 5.2000 | 1 | 1 |
| vexibinol | Homo sapiens (human) | Ki | 1.1000 | 1 | 1 |
| (-)-catechin | Homo sapiens (human) | IC50 | 30.0000 | 1 | 1 |
| heraclenol | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| 1-aminoisoquinoline | Homo sapiens (human) | IC50 | 2,000.0000 | 1 | 1 |
| rivastigmine | Homo sapiens (human) | IC50 | 9.3950 | 1 | 2 |
| columbianetin, (s)-isomer | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| phellopterin | Homo sapiens (human) | IC50 | 1,432.0000 | 1 | 1 |
| gefitinib | Homo sapiens (human) | IC50 | 20.0000 | 1 | 1 |
| n(6)-(3-iodobenzyl)-5'-n-methylcarboxamidoadenosine | Homo sapiens (human) | Ki | 0.0540 | 1 | 1 |
| phlorofucofuroeckol a | Homo sapiens (human) | IC50 | 2.1300 | 1 | 1 |
| phlorofucofuroeckol a | Homo sapiens (human) | Ki | 1.3000 | 1 | 1 |
| eckol | Homo sapiens (human) | IC50 | 12.2000 | 1 | 1 |
| eckol | Homo sapiens (human) | Ki | 13.9000 | 1 | 1 |
| (+)-epicatechin | Homo sapiens (human) | IC50 | 25.5000 | 1 | 2 |
| a-130a | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| marmesin | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| latifolin | Homo sapiens (human) | IC50 | 180.0000 | 1 | 1 |
| decursin | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| decursinol | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| eugeniin | Homo sapiens (human) | IC50 | 3.1000 | 1 | 1 |
| eugeniin | Homo sapiens (human) | Ki | 6.8400 | 1 | 1 |
| om99-2 | Homo sapiens (human) | IC50 | 3.5952 | 20 | 21 |
| om99-2 | Homo sapiens (human) | Ki | 0.1618 | 20 | 20 |
| om00-3 | Homo sapiens (human) | IC50 | 0.0060 | 2 | 2 |
| om00-3 | Homo sapiens (human) | Ki | 0.0006 | 3 | 3 |
| heraclenin | Homo sapiens (human) | IC50 | 443.6000 | 1 | 1 |
| isoxanthohumol | Homo sapiens (human) | IC50 | 27.7000 | 1 | 1 |
| lomatin | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| 2,2'-dihydroxychalcone | Homo sapiens (human) | IC50 | 60.0000 | 1 | 1 |
| isoliquiritigenin | Homo sapiens (human) | IC50 | 42.2500 | 2 | 2 |
| cnidilin | Homo sapiens (human) | IC50 | 3,442.0000 | 1 | 1 |
| curcumin | Homo sapiens (human) | IC50 | 343.0000 | 1 | 1 |
| aurapten | Homo sapiens (human) | IC50 | 345.1000 | 1 | 1 |
| dieckol | Homo sapiens (human) | IC50 | 2.2100 | 1 | 1 |
| dieckol | Homo sapiens (human) | Ki | 1.5000 | 1 | 1 |
| 2-chloro-n(6)-(3-iodobenzyl)adenosine-5'-n-methyluronamide | Homo sapiens (human) | Ki | 1.2400 | 1 | 1 |
| byakangelicol | Homo sapiens (human) | IC50 | 104.9000 | 1 | 1 |
| ginkgetin | Homo sapiens (human) | IC50 | 4.1800 | 1 | 1 |
| gallocatechin-3-gallate | Homo sapiens (human) | IC50 | 1.8000 | 1 | 1 |
| gallocatechin-3-gallate | Homo sapiens (human) | Ki | 0.1700 | 1 | 1 |
| quercetin | Homo sapiens (human) | IC50 | 7.6400 | 3 | 3 |
| quercetin | Homo sapiens (human) | Ki | 14.0000 | 1 | 1 |
| bergaptol | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| apigenin | Homo sapiens (human) | IC50 | 38.5000 | 1 | 1 |
| butein | Homo sapiens (human) | IC50 | 2.3700 | 1 | 1 |
| esculetin | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| 7-hydroxycoumarin | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| amentoflavone | Homo sapiens (human) | IC50 | 1.5400 | 1 | 1 |
| cupressuflavone | Homo sapiens (human) | IC50 | 10.0000 | 1 | 1 |
| hinokiflavone | Homo sapiens (human) | IC50 | 10.0000 | 1 | 1 |
| morin | Homo sapiens (human) | IC50 | 12.3000 | 1 | 1 |
| morusin | Homo sapiens (human) | IC50 | 59.4000 | 1 | 1 |
| morusin | Homo sapiens (human) | Ki | 64.1000 | 1 | 1 |
| myricetin | Homo sapiens (human) | IC50 | 3.4900 | 2 | 2 |
| robustaflavone | Homo sapiens (human) | IC50 | 10.0000 | 1 | 1 |
| sciadopitysin | Homo sapiens (human) | IC50 | 10.0000 | 1 | 1 |
| ellagic acid | Homo sapiens (human) | IC50 | 3.9000 | 1 | 1 |
| bilobetin | Homo sapiens (human) | IC50 | 2.0200 | 1 | 1 |
| 7-demethylsuberosin | Homo sapiens (human) | IC50 | 412.9000 | 1 | 1 |
| 8-geranyloxypsoralen | Homo sapiens (human) | IC50 | 20.4000 | 1 | 1 |
| 8-geranyloxypsoralen | Homo sapiens (human) | Ki | 61.7500 | 2 | 2 |
| isoginkgetin | Homo sapiens (human) | IC50 | 3.0100 | 1 | 1 |
| osthenol | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| podocarpusflavone a | Homo sapiens (human) | IC50 | 0.9900 | 1 | 1 |
| grifolin | Homo sapiens (human) | IC50 | 6.1000 | 1 | 1 |
| bergamottin | Homo sapiens (human) | IC50 | 32.2000 | 1 | 1 |
| bergamottin | Homo sapiens (human) | Ki | 17.7500 | 2 | 2 |
| l 685458 | Homo sapiens (human) | IC50 | 0.3000 | 1 | 1 |
| morusinol | Homo sapiens (human) | IC50 | 135.9000 | 1 | 1 |
| Norartocarpetin | Homo sapiens (human) | IC50 | 60.6000 | 1 | 1 |
| Norartocarpetin | Homo sapiens (human) | Ki | 82.6000 | 1 | 1 |
| sequoiaflavone | Homo sapiens (human) | IC50 | 1.4000 | 1 | 1 |
| w-13 | Homo sapiens (human) | IC50 | 10.0000 | 1 | 1 |
| 2,4,2'-trihydroxychalcone | Homo sapiens (human) | IC50 | 2.4500 | 1 | 1 |
| 4-hydroxylonchocarpin | Homo sapiens (human) | IC50 | 9.8000 | 1 | 1 |
| (-)-catechin-3-O-gallate | Homo sapiens (human) | IC50 | 6.0000 | 1 | 1 |
| kmi-420 | Homo sapiens (human) | IC50 | 0.0082 | 7 | 7 |
| kmi-429 | Homo sapiens (human) | IC50 | 0.0039 | 7 | 7 |
| bis(7)-tacrine | Homo sapiens (human) | IC50 | 7.5000 | 3 | 3 |
| memoquin | Homo sapiens (human) | IC50 | 0.8567 | 6 | 6 |
| cnidicin | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| 2,4,2',4'-Tetrahydroxychalcone | Homo sapiens (human) | IC50 | 0.6200 | 1 | 1 |
| sargahydroquinoic acid | Homo sapiens (human) | IC50 | 4.4000 | 1 | 1 |
| sargahydroquinoic acid | Homo sapiens (human) | Ki | 1.6000 | 1 | 1 |
| eckstolonol | Homo sapiens (human) | IC50 | 5.3500 | 1 | 1 |
| eckstolonol | Homo sapiens (human) | Ki | 8.0000 | 1 | 1 |
| sargachromenol | Homo sapiens (human) | IC50 | 7.0000 | 1 | 1 |
| sargachromenol | Homo sapiens (human) | Ki | 2.9000 | 1 | 1 |
| 7-phloroeckol | Homo sapiens (human) | IC50 | 8.5900 | 1 | 1 |
| 7-phloroeckol | Homo sapiens (human) | Ki | 7.2000 | 1 | 1 |
| tasiamide b | Homo sapiens (human) | IC50 | 0.3530 | 1 | 1 |
| boeravinone e | Homo sapiens (human) | IC50 | 5.6000 | 1 | 1 |
| sesone | Homo sapiens (human) | IC50 | 0.3000 | 1 | 1 |
| 2'-methoxykurarinone | Homo sapiens (human) | IC50 | 6.7000 | 1 | 1 |
| 2'-methoxykurarinone | Homo sapiens (human) | Ki | 10.6000 | 1 | 1 |
| gsk188909 | Homo sapiens (human) | IC50 | 0.2454 | 10 | 12 |
| 6-(3,5-difluoroanilino)-9-ethyl-2-purinecarbonitrile | Homo sapiens (human) | IC50 | 63.0957 | 1 | 1 |
| ly2811376 | Homo sapiens (human) | IC50 | 0.2764 | 14 | 14 |
| grassystatin a | Homo sapiens (human) | IC50 | 10.0000 | 2 | 2 |
| Kushenol A | Homo sapiens (human) | IC50 | 2.6000 | 1 | 1 |
| Kushenol A | Homo sapiens (human) | Ki | 3.0000 | 1 | 1 |
| kurarinol | Homo sapiens (human) | IC50 | 39.2000 | 1 | 1 |
| leachianone a | Homo sapiens (human) | IC50 | 8.4000 | 1 | 1 |
| leachianone a | Homo sapiens (human) | Ki | 3.9000 | 1 | 1 |
| azd3839 | Homo sapiens (human) | IC50 | 0.0175 | 3 | 3 |
| azd3839 | Homo sapiens (human) | Ki | 0.0257 | 1 | 1 |
| ly2886721 | Homo sapiens (human) | IC50 | 0.0150 | 5 | 5 |
| ass234 | Homo sapiens (human) | IC50 | 0.4600 | 1 | 1 |
Drugs with Activation Measurements
Drugs with Other Measurements
| Drug | Taxonomy | Measurement | Average (mM) | Bioassay(s) | Publication(s) |
|---|
| om99-2 | Homo sapiens (human) | INH | 0.2500 | 1 | 1 |
| apigenin | Homo sapiens (human) | Kic | 11.3100 | 1 | 1 |
| ly2811376 | Homo sapiens (human) | INH | 0.2700 | 2 | 2 |
Design, synthesis, and multitargeted profiling of N-benzylpyrrolidine derivatives for the treatment of Alzheimer's disease.Bioorganic & medicinal chemistry, , 11-15, Volume: 28, Issue:22, 2020
Design and development of molecular hybrids of 2-pyridylpiperazine and 5-phenyl-1,3,4-oxadiazoles as potential multifunctional agents to treat Alzheimer's disease.European journal of medicinal chemistry, , Dec-01, Volume: 183, 2019
Design and development of multitarget-directed N-Benzylpiperidine analogs as potential candidates for the treatment of Alzheimer's disease.European journal of medicinal chemistry, , Apr-01, Volume: 167, 2019
Multipotent AChE and BACE-1 inhibitors for the treatment of Alzheimer's disease: Design, synthesis and bio-analysis of 7-amino-1,4-dihydro-2H-isoquilin-3-one derivates.European journal of medicinal chemistry, , Sep-29, Volume: 138, 2017
Development and evaluation of multifunctional agents for potential treatment of Alzheimer's disease: application to a pyrimidine-2,4-diamine template.Bioorganic & medicinal chemistry letters, , Jul-15, Volume: 22, Issue:14, 2012
Structure-activity relationships for naturally occurring coumarins as β-secretase inhibitor.Bioorganic & medicinal chemistry, , Jan-15, Volume: 20, Issue:2, 2012
Biotransformation of isoimperatorin and imperatorin by Glomerella cingulata and beta-secretase inhibitory activity.Bioorganic & medicinal chemistry, , Jan-01, Volume: 18, Issue:1, 2010
Fragment based drug discovery: practical implementation based on ¹⁹F NMR spectroscopy.Journal of medicinal chemistry, , Jan-26, Volume: 55, Issue:2, 2012
From fragment screening to in vivo efficacy: optimization of a series of 2-aminoquinolines as potent inhibitors of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1).Journal of medicinal chemistry, , Aug-25, Volume: 54, Issue:16, 2011
Application of fragment screening by X-ray crystallography to the discovery of aminopyridines as inhibitors of beta-secretase.Journal of medicinal chemistry, , Mar-22, Volume: 50, Issue:6, 2007
Structure-activity relationships for naturally occurring coumarins as β-secretase inhibitor.Bioorganic & medicinal chemistry, , Jan-15, Volume: 20, Issue:2, 2012
Biotransformation of isoimperatorin and imperatorin by Glomerella cingulata and beta-secretase inhibitory activity.Bioorganic & medicinal chemistry, , Jan-01, Volume: 18, Issue:1, 2010
Design, synthesis, and biological evaluation of novel 4-oxobenzo[d]1,2,3-triazin-benzylpyridinum derivatives as potent anti-Alzheimer agents.Bioorganic & medicinal chemistry, , 07-01, Volume: 27, Issue:13, 2019
A phenotypic approach to the discovery of compounds that promote non-amyloidogenic processing of the amyloid precursor protein: Toward a new profile of indirect β-secretase inhibitors.European journal of medicinal chemistry, , Nov-05, Volume: 159, 2018
Novel tetrahydrocarbazole benzyl pyridine hybrids as potent and selective butryl cholinesterase inhibitors with neuroprotective and β-secretase inhibition activities.European journal of medicinal chemistry, , Jul-15, Volume: 155, 2018
Discovery of imidazopyridines containing isoindoline-1,3-dione framework as a new class of BACE1 inhibitors: Design, synthesis and SAR analysis.European journal of medicinal chemistry, , Sep-29, Volume: 138, 2017
Multifunctional iminochromene-2H-carboxamide derivatives containing different aminomethylene triazole with BACE1 inhibitory, neuroprotective and metal chelating properties targeting Alzheimer's disease.European journal of medicinal chemistry, , Dec-01, Volume: 141, 2017
Synthesis, docking study and neuroprotective effects of some novel pyrano[3,2-c]chromene derivatives bearing morpholine/phenylpiperazine moiety.Bioorganic & medicinal chemistry, , 08-01, Volume: 25, Issue:15, 2017
Design and synthesis of novel anti-Alzheimer's agents: Acridine-chromenone and quinoline-chromenone hybrids.Bioorganic chemistry, , Volume: 67, 2016
Peptidomimetic β-Secretase Inhibitors Comprising a Sequence of Amyloid-β Peptide for Alzheimer's Disease.Journal of medicinal chemistry, , Jul-23, Volume: 58, Issue:14, 2015
Structure-based design of β-site APP cleaving enzyme 1 (BACE1) inhibitors for the treatment of Alzheimer's disease.Journal of medicinal chemistry, , Jun-13, Volume: 56, Issue:11, 2013
Phenylimino-2H-chromen-3-carboxamide derivatives as novel small molecule inhibitors of β-secretase (BACE1).Bioorganic & medicinal chemistry, , Apr-15, Volume: 21, Issue:8, 2013
Hydroxyethylamine-based inhibitors of BACE1: P₁-P₃ macrocyclization can improve potency, selectivity, and cell activity.Bioorganic & medicinal chemistry letters, , Aug-01, Volume: 23, Issue:15, 2013
Discovery of cyclic sulfone hydroxyethylamines as potent and selective β-site APP-cleaving enzyme 1 (BACE1) inhibitors: structure-based design and in vivo reduction of amyloid β-peptides.Journal of medicinal chemistry, , Apr-12, Volume: 55, Issue:7, 2012
Structure-based design, synthesis, and biological evaluation of dihydroquinazoline-derived potent β-secretase inhibitors.Bioorganic & medicinal chemistry letters, , Sep-01, Volume: 22, Issue:17, 2012
Structure-based design of highly selective β-secretase inhibitors: synthesis, biological evaluation, and protein-ligand X-ray crystal structure.Journal of medicinal chemistry, , Nov-08, Volume: 55, Issue:21, 2012
Synthesis and in vivo evaluation of cyclic diaminopropane BACE-1 inhibitors.Bioorganic & medicinal chemistry letters, , Nov-15, Volume: 21, Issue:22, 2011
Searching for the Multi-Target-Directed Ligands against Alzheimer's disease: discovery of quinoxaline-based hybrid compounds with AChE, H₃R and BACE 1 inhibitory activities.Bioorganic & medicinal chemistry, , Dec-01, Volume: 19, Issue:23, 2011
On a possible neutral charge state for the catalytic dyad in β-secretase when bound to hydroxyethylene transition state analogue inhibitors.Journal of medicinal chemistry, , Apr-28, Volume: 54, Issue:8, 2011
Dual-target-directed 1,3-diphenylurea derivatives: BACE 1 inhibitor and metal chelator against Alzheimer's disease.Bioorganic & medicinal chemistry, , Aug-01, Volume: 18, Issue:15, 2010
Design and synthesis of 5,5'-disubstituted aminohydantoins as potent and selective human beta-secretase (BACE1) inhibitors.Journal of medicinal chemistry, , Feb-11, Volume: 53, Issue:3, 2010
Aminoimidazoles as potent and selective human beta-secretase (BACE1) inhibitors.Journal of medicinal chemistry, , Oct-22, Volume: 52, Issue:20, 2009
Discovery of novel non-peptide inhibitors of BACE-1 using virtual high-throughput screening.Bioorganic & medicinal chemistry letters, , Dec-01, Volume: 19, Issue:23, 2009
Structure-based design and synthesis of macrocyclic peptidomimetic beta-secretase (BACE-1) inhibitors.Bioorganic & medicinal chemistry letters, , Mar-01, Volume: 19, Issue:5, 2009
Rational design and synthesis of potent dibenzazepine motifs as beta-secretase inhibitors.Journal of medicinal chemistry, , Oct-22, Volume: 52, Issue:20, 2009
Harnessing nature's insight: design of aspartyl protease inhibitors from treatment of drug-resistant HIV to Alzheimer's disease.Journal of medicinal chemistry, , Apr-23, Volume: 52, Issue:8, 2009
Design, synthesis and biological evaluation of novel dual inhibitors of acetylcholinesterase and beta-secretase.Bioorganic & medicinal chemistry, , Feb-15, Volume: 17, Issue:4, 2009
Tyramine fragment binding to BACE-1.Bioorganic & medicinal chemistry letters, , Feb-15, Volume: 18, Issue:4, 2008
Potent memapsin 2 (beta-secretase) inhibitors: design, synthesis, protein-ligand X-ray structure, and in vivo evaluation.Bioorganic & medicinal chemistry letters, , Feb-01, Volume: 18, Issue:3, 2008
Discovery of a novel warhead against beta-secretase through fragment-based lead generation.Journal of medicinal chemistry, , Nov-29, Volume: 50, Issue:24, 2007
Design, synthesis and X-ray structure of protein-ligand complexes: important insight into selectivity of memapsin 2 (beta-secretase) inhibitors.Journal of the American Chemical Society, , Apr-26, Volume: 128, Issue:16, 2006
Structure-based design of cycloamide-urethane-derived novel inhibitors of human brain memapsin 2 (beta-secretase).Bioorganic & medicinal chemistry letters, , Jan-03, Volume: 15, Issue:1, 2005
Structure-based design, synthesis, and memapsin 2 (BACE) inhibitory activity of carbocyclic and heterocyclic peptidomimetics.Journal of medicinal chemistry, , Aug-11, Volume: 48, Issue:16, 2005
Phe*-Ala-based pentapeptide mimetics are BACE inhibitors: P2 and P3 SAR.Bioorganic & medicinal chemistry letters, , Jan-05, Volume: 14, Issue:1, 2004
Modeling the binding affinities of beta-secretase inhibitors: application to subsite specificity.Bioorganic & medicinal chemistry letters, , Oct-04, Volume: 14, Issue:19, 2004
Human beta-secretase (BACE) and BACE inhibitors.Journal of medicinal chemistry, , Oct-23, Volume: 46, Issue:22, 2003
Design and synthesis of statine-containing BACE inhibitors.Bioorganic & medicinal chemistry letters, , Dec-15, Volume: 13, Issue:24, 2003
Calculation of the binding affinity of beta-secretase inhibitors using the linear interaction energy method.Journal of medicinal chemistry, , May-22, Volume: 46, Issue:11, 2003
Structure-based design: potent inhibitors of human brain memapsin 2 (beta-secretase).Journal of medicinal chemistry, , Aug-30, Volume: 44, Issue:18, 2001
Peptidomimetic β-Secretase Inhibitors Comprising a Sequence of Amyloid-β Peptide for Alzheimer's Disease.Journal of medicinal chemistry, , Jul-23, Volume: 58, Issue:14, 2015
On a possible neutral charge state for the catalytic dyad in β-secretase when bound to hydroxyethylene transition state analogue inhibitors.Journal of medicinal chemistry, , Apr-28, Volume: 54, Issue:8, 2011
Prolonged stability by cyclization: Macrocyclic phosphino dipeptide isostere inhibitors of beta-secretase (BACE1).Bioorganic & medicinal chemistry letters, , Aug-01, Volume: 19, Issue:15, 2009
Synthesis and biological evaluation of phosphino dipeptide isostere inhibitor of human beta-secretase (BACE1).Bioorganic & medicinal chemistry, , Jun-15, Volume: 15, Issue:12, 2007
Lodopyridones B and C from a marine sediment-derived bacterium Saccharomonospora sp.Bioorganic & medicinal chemistry letters, , 07-15, Volume: 27, Issue:14, 2017
Design, synthesis and SAR study of hydroxychalcone inhibitors of human β-secretase (BACE1).Journal of enzyme inhibition and medicinal chemistry, , Volume: 26, Issue:5, 2011
BACE1 inhibitory activity and molecular docking analysis of meroterpenoids from Sargassum serratifolium.Bioorganic & medicinal chemistry, , 08-01, Volume: 25, Issue:15, 2017
Isolation of cholinesterase and β-secretase 1 inhibiting compounds from Lycopodiella cernua.Bioorganic & medicinal chemistry, , Jul-01, Volume: 23, Issue:13, 2015
Molecular docking studies of phlorotannins from Eisenia bicyclis with BACE1 inhibitory activity.Bioorganic & medicinal chemistry letters, , Jun-01, Volume: 20, Issue:11, 2010
Tripeptidic BACE1 inhibitors devised by in-silico conformational structure-based design.Bioorganic & medicinal chemistry letters, , Jan-15, Volume: 22, Issue:2, 2012
Investigation of α-phenylnorstatine and α-benzylnorstatine as transition state isostere motifs in the search for new BACE-1 inhibitors.Bioorganic & medicinal chemistry, , Jan-01, Volume: 19, Issue:1, 2011
Structure-guided design and synthesis of P1' position 1-phenylcycloalkylamine-derived pentapeptidic BACE1 inhibitors.Bioorganic & medicinal chemistry, , Sep-01, Volume: 19, Issue:17, 2011
BACE1 inhibitors: optimization by replacing the P1' residue with non-acidic moiety.Bioorganic & medicinal chemistry letters, , Mar-01, Volume: 18, Issue:5, 2008
Novel non-peptidic and small-sized BACE1 inhibitors.Bioorganic & medicinal chemistry letters, , Mar-01, Volume: 18, Issue:5, 2008
Design and synthesis of potent beta-secretase (BACE1) inhibitors with P1' carboxylic acid bioisosteres.Bioorganic & medicinal chemistry letters, , May-01, Volume: 16, Issue:9, 2006
Design and synthesis of highly active Alzheimer's beta-secretase (BACE1) inhibitors, KMI-420 and KMI-429, with enhanced chemical stability.Bioorganic & medicinal chemistry letters, , Jan-03, Volume: 15, Issue:1, 2005
Novel β-amyloid aggregation inhibitors possessing a turn mimic.Bioorganic & medicinal chemistry letters, , Apr-01, Volume: 25, Issue:7, 2015
Tripeptidic BACE1 inhibitors devised by in-silico conformational structure-based design.Bioorganic & medicinal chemistry letters, , Jan-15, Volume: 22, Issue:2, 2012
Structure-guided design and synthesis of P1' position 1-phenylcycloalkylamine-derived pentapeptidic BACE1 inhibitors.Bioorganic & medicinal chemistry, , Sep-01, Volume: 19, Issue:17, 2011
BACE1 inhibitors: optimization by replacing the P1' residue with non-acidic moiety.Bioorganic & medicinal chemistry letters, , Mar-01, Volume: 18, Issue:5, 2008
Novel non-peptidic and small-sized BACE1 inhibitors.Bioorganic & medicinal chemistry letters, , Mar-01, Volume: 18, Issue:5, 2008
Design and synthesis of potent beta-secretase (BACE1) inhibitors with P1' carboxylic acid bioisosteres.Bioorganic & medicinal chemistry letters, , May-01, Volume: 16, Issue:9, 2006
Design and synthesis of highly active Alzheimer's beta-secretase (BACE1) inhibitors, KMI-420 and KMI-429, with enhanced chemical stability.Bioorganic & medicinal chemistry letters, , Jan-03, Volume: 15, Issue:1, 2005
Huprine-tacrine heterodimers as anti-amyloidogenic compounds of potential interest against Alzheimer's and prion diseases.Journal of medicinal chemistry, , Jan-26, Volume: 55, Issue:2, 2012
Multi-target strategy to address Alzheimer's disease: design, synthesis and biological evaluation of new tacrine-based dimers.European journal of medicinal chemistry, , Volume: 46, Issue:9, 2011
Pyrano[3,2-c]quinoline-6-chlorotacrine hybrids as a novel family of acetylcholinesterase- and beta-amyloid-directed anti-Alzheimer compounds.Journal of medicinal chemistry, , Sep-10, Volume: 52, Issue:17, 2009
Alzheimer's disease: Updated multi-targets therapeutics are in clinical and in progress.European journal of medicinal chemistry, , Aug-05, Volume: 238, 2022
Novel Tacrine-Benzofuran Hybrids as Potent Multitarget-Directed Ligands for the Treatment of Alzheimer's Disease: Design, Synthesis, Biological Evaluation, and X-ray Crystallography.Journal of medicinal chemistry, , Jan-14, Volume: 59, Issue:1, 2016
Synthesis and multitarget biological profiling of a novel family of rhein derivatives as disease-modifying anti-Alzheimer agents.Journal of medicinal chemistry, , Mar-27, Volume: 57, Issue:6, 2014
Synthesis of monomeric derivatives to probe memoquin's bivalent interactions.Journal of medicinal chemistry, , Dec-22, Volume: 54, Issue:24, 2011
Polyamines in drug discovery: from the universal template approach to the multitarget-directed ligand design strategy.Journal of medicinal chemistry, , Aug-26, Volume: 53, Issue:16, 2010
Multi-target-directed ligands to combat neurodegenerative diseases.Journal of medicinal chemistry, , Feb-14, Volume: 51, Issue:3, 2008
Second generation of BACE-1 inhibitors. Part 1: The need for improved pharmacokinetics.Bioorganic & medicinal chemistry letters, , Jul-01, Volume: 19, Issue:13, 2009
BACE-1 inhibitors part 3: identification of hydroxy ethylamines (HEAs) with nanomolar potency in cells.Bioorganic & medicinal chemistry letters, , Feb-01, Volume: 18, Issue:3, 2008
Meroterpenoids produced by fungi: Occurrence, structural diversity, biological activities, and their molecular targets.European journal of medicinal chemistry, , Jan-01, Volume: 209, 2021
Discovery and Early Clinical Development of LY3202626, a Low-Dose, CNS-Penetrant BACE Inhibitor.Journal of medicinal chemistry, , 06-24, Volume: 64, Issue:12, 2021
Preparation and biological evaluation of BACE1 inhibitors: Leveraging trans-cyclopropyl moieties as ligand efficient conformational constraints.Bioorganic & medicinal chemistry, , 01-01, Volume: 28, Issue:1, 2020
New evolutions in the BACE1 inhibitor field from 2014 to 2018.Bioorganic & medicinal chemistry letters, , 03-15, Volume: 29, Issue:6, 2019
Design, synthesis and evaluation of 2-amino-imidazol-4-one derivatives as potent β-site amyloid precursor protein cleaving enzyme 1 (BACE-1) inhibitors.Bioorganic & medicinal chemistry letters, , 12-15, Volume: 29, Issue:24, 2019
[no title available]Bioorganic & medicinal chemistry, , 09-15, Volume: 26, Issue:17, 2018
Design and Synthesis of Clinical Candidate PF-06751979: A Potent, Brain Penetrant, β-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Inhibitor Lacking Hypopigmentation.Journal of medicinal chemistry, , 05-24, Volume: 61, Issue:10, 2018
BACE-1 Inhibitors: From Recent Single-Target Molecules to Multitarget Compounds for Alzheimer's Disease.Journal of medicinal chemistry, , 02-08, Volume: 61, Issue:3, 2018
BACE1 Inhibitory Meroterpenoids from Aspergillus terreus.Journal of natural products, , 09-28, Volume: 81, Issue:9, 2018
Discovery of furo[2,3-d][1,3]thiazinamines as beta amyloid cleaving enzyme-1 (BACE1) inhibitors.Bioorganic & medicinal chemistry letters, , 12-01, Volume: 26, Issue:23, 2016
Targeting the BACE1 Active Site Flap Leads to a Potent Inhibitor That Elicits Robust Brain Aβ Reduction in Rodents.ACS medicinal chemistry letters, , Mar-10, Volume: 7, Issue:3, 2016
The evolution of amidine-based brain penetrant BACE1 inhibitors.Bioorganic & medicinal chemistry letters, , May-01, Volume: 24, Issue:9, 2014
Structure-based design of β-site APP cleaving enzyme 1 (BACE1) inhibitors for the treatment of Alzheimer's disease.Journal of medicinal chemistry, , Jun-13, Volume: 56, Issue:11, 2013
Cyanobacterial peptides as a prototype for the design of potent β-secretase inhibitors and the development of selective chemical probes for other aspartic proteases.Journal of medicinal chemistry, , Dec-13, Volume: 55, Issue:23, 2012
Grassystatins A-C from marine cyanobacteria, potent cathepsin E inhibitors that reduce antigen presentation.Journal of medicinal chemistry, , Sep-24, Volume: 52, Issue:18, 2009
Toward β-Secretase-1 Inhibitors with Improved Isoform Selectivity.Journal of medicinal chemistry, , 04-26, Volume: 61, Issue:8, 2018
Mapping the Efficiency and Physicochemical Trajectories of Successful Optimizations.Journal of medicinal chemistry, , 08-09, Volume: 61, Issue:15, 2018
Design and synthesis of β-site amyloid precursor protein cleaving enzyme (BACE1) inhibitors with in vivo brain reduction of β-amyloid peptides.Journal of medicinal chemistry, , Nov-08, Volume: 55, Issue:21, 2012
Discovery and Early Clinical Development of LY3202626, a Low-Dose, CNS-Penetrant BACE Inhibitor.Journal of medicinal chemistry, , 06-24, Volume: 64, Issue:12, 2021
Preparation and biological evaluation of BACE1 inhibitors: Leveraging trans-cyclopropyl moieties as ligand efficient conformational constraints.Bioorganic & medicinal chemistry, , 01-01, Volume: 28, Issue:1, 2020
Discovery of furo[2,3-d][1,3]thiazinamines as beta amyloid cleaving enzyme-1 (BACE1) inhibitors.Bioorganic & medicinal chemistry letters, , 12-01, Volume: 26, Issue:23, 2016
The evolution of amidine-based brain penetrant BACE1 inhibitors.Bioorganic & medicinal chemistry letters, , May-01, Volume: 24, Issue:9, 2014
Enables
This protein enables 8 target(s):
| Target | Category | Definition |
|---|
| amyloid-beta binding | molecular function | Binding to an amyloid-beta peptide/protein. [GOC:hjd] |
| endopeptidase activity | molecular function | Catalysis of the hydrolysis of internal, alpha-peptide bonds in a polypeptide chain. [http://merops.sanger.ac.uk/about/glossary.htm#ENDOPEPTIDASE] |
| aspartic-type endopeptidase activity | molecular function | Catalysis of the hydrolysis of internal, alpha-peptide bonds in a polypeptide chain by a mechanism in which a water molecule bound by the side chains of aspartic residues at the active center acts as a nucleophile. [ISBN:0198506732] |
| protein binding | molecular function | Binding to a protein. [GOC:go_curators] |
| peptidase activity | molecular function | Catalysis of the hydrolysis of a peptide bond. A peptide bond is a covalent bond formed when the carbon atom from the carboxyl group of one amino acid shares electrons with the nitrogen atom from the amino group of a second amino acid. [GOC:jl, ISBN:0815332181] |
| beta-aspartyl-peptidase activity | molecular function | Catalysis of the cleavage of a beta-linked aspartic residue from the N-terminus of a polypeptide. [EC:3.4.19.5] |
| enzyme binding | molecular function | Binding to an enzyme, a protein with catalytic activity. [GOC:jl] |
| protein serine/threonine kinase binding | molecular function | Binding to a protein serine/threonine kinase. [GOC:krc, GOC:sl, PMID:28608965] |
Located In
This protein is located in 20 target(s):
| Target | Category | Definition |
|---|
| lysosome | cellular component | A small lytic vacuole that has cell cycle-independent morphology found in most animal cells and that contains a variety of hydrolases, most of which have their maximal activities in the pH range 5-6. The contained enzymes display latency if properly isolated. About 40 different lysosomal hydrolases are known and lysosomes have a great variety of morphologies and functions. [GOC:mah, ISBN:0198506732] |
| endosome | cellular component | A vacuole to which materials ingested by endocytosis are delivered. [ISBN:0198506732, PMID:19696797] |
| early endosome | cellular component | A membrane-bounded organelle that receives incoming material from primary endocytic vesicles that have been generated by clathrin-dependent and clathrin-independent endocytosis; vesicles fuse with the early endosome to deliver cargo for sorting into recycling or degradation pathways. [GOC:mah, NIF_Subcellular:nlx_subcell_20090701, PMID:19696797] |
| late endosome | cellular component | A prelysosomal endocytic organelle differentiated from early endosomes by lower lumenal pH and different protein composition. Late endosomes are more spherical than early endosomes and are mostly juxtanuclear, being concentrated near the microtubule organizing center. [NIF_Subcellular:nlx_subcell_20090702, PMID:11964142, PMID:2557062] |
| multivesicular body | cellular component | A type of endosome in which regions of the limiting endosomal membrane invaginate to form internal vesicles; membrane proteins that enter the internal vesicles are sequestered from the cytoplasm. [PMID:11566881, PMID:16533950] |
| endoplasmic reticulum lumen | cellular component | The volume enclosed by the membranes of the endoplasmic reticulum. [ISBN:0198547684] |
| Golgi apparatus | cellular component | A membrane-bound cytoplasmic organelle of the endomembrane system that further processes the core oligosaccharides (e.g. N-glycans) added to proteins in the endoplasmic reticulum and packages them into membrane-bound vesicles. The Golgi apparatus operates at the intersection of the secretory, lysosomal, and endocytic pathways. [ISBN:0198506732] |
| trans-Golgi network | cellular component | The network of interconnected tubular and cisternal structures located within the Golgi apparatus on the side distal to the endoplasmic reticulum, from which secretory vesicles emerge. The trans-Golgi network is important in the later stages of protein secretion where it is thought to play a key role in the sorting and targeting of secreted proteins to the correct destination. [GOC:vw, ISBN:0815316194] |
| plasma membrane | cellular component | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. [ISBN:0716731363] |
| synaptic vesicle | cellular component | A secretory organelle, typically 50 nm in diameter, of presynaptic nerve terminals; accumulates in high concentrations of neurotransmitters and secretes these into the synaptic cleft by fusion with the 'active zone' of the presynaptic plasma membrane. [PMID:10099709, PMID:12563290] |
| cell surface | cellular component | The external part of the cell wall and/or plasma membrane. [GOC:jl, GOC:mtg_sensu, GOC:sm] |
| endosome membrane | cellular component | The lipid bilayer surrounding an endosome. [GOC:mah] |
| membrane | cellular component | A lipid bilayer along with all the proteins and protein complexes embedded in it and attached to it. [GOC:dos, GOC:mah, ISBN:0815316194] |
| axon | cellular component | The long process of a neuron that conducts nerve impulses, usually away from the cell body to the terminals and varicosities, which are sites of storage and release of neurotransmitter. [GOC:nln, ISBN:0198506732] |
| dendrite | cellular component | A neuron projection that has a short, tapering, morphology. Dendrites receive and integrate signals from other neurons or from sensory stimuli, and conduct nerve impulses towards the axon or the cell body. In most neurons, the impulse is conveyed from dendrites to axon via the cell body, but in some types of unipolar neuron, the impulse does not travel via the cell body. [GOC:aruk, GOC:bc, GOC:dos, GOC:mah, GOC:nln, ISBN:0198506732] |
| neuronal cell body | cellular component | The portion of a neuron that includes the nucleus, but excludes cell projections such as axons and dendrites. [GOC:go_curators] |
| membrane raft | cellular component | Any of the small (10-200 nm), heterogeneous, highly dynamic, sterol- and sphingolipid-enriched membrane domains that compartmentalize cellular processes. Small rafts can sometimes be stabilized to form larger platforms through protein-protein and protein-lipid interactions. [PMID:16645198, PMID:20044567] |
| recycling endosome | cellular component | An organelle consisting of a network of tubules that functions in targeting molecules, such as receptors transporters and lipids, to the plasma membrane. [GOC:dph, GOC:jid, GOC:kmv, GOC:rph, PMID:10930469, PMID:15601896, PMID:16246101, PMID:21556374, PMID:21562044] |
| Golgi-associated vesicle lumen | cellular component | The volume enclosed by the membrane of a Golgi-associated vesicle. [GOC:mah] |
| hippocampal mossy fiber to CA3 synapse | cellular component | One of the giant synapses that form between the mossy fiber axons of dentate gyrus granule cells and the large complex spines of CA3 pyramidal cells. It consists of a giant bouton known as the mossy fiber expansion, synapsed to the complex, multiheaded spine (thorny excresence) of a CA3 pyramidal cell. [DOI:10.1002/1096-9861, PMID:13869693, PMID:23264762] |
Active In
This protein is active in 3 target(s):
| Target | Category | Definition |
|---|
| endosome | cellular component | A vacuole to which materials ingested by endocytosis are delivered. [ISBN:0198506732, PMID:19696797] |
| plasma membrane | cellular component | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. [ISBN:0716731363] |
| trans-Golgi network | cellular component | The network of interconnected tubular and cisternal structures located within the Golgi apparatus on the side distal to the endoplasmic reticulum, from which secretory vesicles emerge. The trans-Golgi network is important in the later stages of protein secretion where it is thought to play a key role in the sorting and targeting of secreted proteins to the correct destination. [GOC:vw, ISBN:0815316194] |
Involved In
This protein is involved in 16 target(s):
| Target | Category | Definition |
|---|
| proteolysis | biological process | The hydrolysis of proteins into smaller polypeptides and/or amino acids by cleavage of their peptide bonds. [GOC:bf, GOC:mah] |
| membrane protein ectodomain proteolysis | biological process | The proteolytic cleavage of transmembrane proteins and release of their ectodomain (extracellular domain). [GOC:jl, http://www.copewithcytokines.de/] |
| response to lead ion | biological process | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lead ion stimulus. [GOC:tair_curators, PMID:16461380] |
| protein processing | biological process | Any protein maturation process achieved by the cleavage of a peptide bond or bonds within a protein. Protein maturation is the process leading to the attainment of the full functional capacity of a protein. [GOC:curators, GOC:jl, GOC:jsg] |
| amyloid-beta formation | biological process | The generation of amyloid-beta by cleavage of the amyloid precursor protein (APP). [GOC:mah] |
| amyloid precursor protein catabolic process | biological process | The chemical reactions and pathways resulting in the breakdown of amyloid precursor protein (APP), the precursor of amyloid-beta, a glycoprotein associated with Alzheimer's disease. [GOC:go_curators] |
| positive regulation of neuron apoptotic process | biological process | Any process that activates or increases the frequency, rate or extent of cell death of neurons by apoptotic process. [GOC:go_curators, GOC:mtg_apoptosis] |
| amyloid-beta metabolic process | biological process | The chemical reactions and pathways involving amyloid-beta, a glycoprotein associated with Alzheimer's disease, and its precursor, amyloid precursor protein (APP). [GOC:ai] |
| detection of mechanical stimulus involved in sensory perception of pain | biological process | The series of events involved in the perception of pain in which a mechanical stimulus is received and converted into a molecular signal. [GOC:ai, GOC:dos] |
| prepulse inhibition | biological process | The process in which a startle magnitude is reduced when the startling stimulus is preceded by a low-intensity prepulse. [GOC:dph, PMID:10341260] |
| cellular response to copper ion | biological process | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a copper ion stimulus. [GOC:mah] |
| cellular response to manganese ion | biological process | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a manganese ion stimulus. [GOC:mah] |
| presynaptic modulation of chemical synaptic transmission | biological process | Any process, acting in the presynapse that results in modulation of chemical synaptic transmission. [GOC:dos] |
| signaling receptor ligand precursor processing | biological process | The cleavage of a peptide bond in a precursor form of a signaling receptor ligand, resulting in the mature (active) form of the ligand. [PMID:29247995] |
| cellular response to amyloid-beta | biological process | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a amyloid-beta stimulus. [GO_REF:0000071, GOC:TermGenie, PMID:23555824] |
| amyloid fibril formation | biological process | The generation of amyloid fibrils, insoluble fibrous protein aggregates exhibiting beta sheet structure, from proteins. [GOC:cvs, GOC:jj, GOC:ppm, GOC:sj, PMID:21148556, PMID:22817896, PMID:28937655, PMID:29654159] |