Page last updated: 2024-08-07 15:42:58
Cathepsin D
A cathepsin D that is encoded in the genome of human. [PRO:DNx, UniProtKB:P07339]
Synonyms
EC 3.4.23.5
Research
Bioassay Publications (34)
| Timeframe | Studies on this Protein(%) | All Drugs % |
|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 2 (5.88) | 18.2507 |
| 2000's | 11 (32.35) | 29.6817 |
| 2010's | 13 (38.24) | 24.3611 |
| 2020's | 8 (23.53) | 2.80 |
Compounds (20)
Drugs with Inhibition Measurements
Drugs with Other Measurements
| Drug | Taxonomy | Measurement | Average (mM) | Bioassay(s) | Publication(s) |
|---|
| pepstatin | Homo sapiens (human) | INH | 0.0001 | 1 | 1 |
| ly2811376 | Homo sapiens (human) | INH | 15.7000 | 1 | 1 |
Plasmepsin Inhibitors in Antimalarial Drug Discovery: Medicinal Chemistry and Target Validation (2000 to Present).Journal of medicinal chemistry, , 05-14, Volume: 63, Issue:9, 2020
Exploiting Structural Dynamics To Design Open-Flap Inhibitors of Malarial Aspartic Proteases.Journal of medicinal chemistry, , 10-24, Volume: 62, Issue:20, 2019
Characterisation of hydrazides and hydrazine derivatives as novel aspartic protease inhibitors.Journal of enzyme inhibition and medicinal chemistry, , Volume: 25, Issue:5, 2010
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, synthesis, and memapsin 2 (BACE) inhibitory activity of carbocyclic and heterocyclic peptidomimetics.Journal of medicinal chemistry, , Aug-11, Volume: 48, Issue:16, 2005
Multiple approaches to repurposing drugs for neuroblastoma.Bioorganic & medicinal chemistry, , 11-01, Volume: 73, 2022
Cathepsin D inhibitors based on tasiamide B derivatives with cell membrane permeability.Bioorganic & medicinal chemistry, , 03-01, Volume: 57, 2022
[no title available]Bioorganic & medicinal chemistry, , 01-01, Volume: 29, 2021
Biomimetic Macrocyclic Inhibitors of Human Cathepsin D: Structure-Activity Relationship and Binding Mode Analysis.Journal of medicinal chemistry, , 02-27, Volume: 63, Issue:4, 2020
Izenamides A and B, Statine-Containing Depsipeptides, and an Analogue from a Marine Cyanobacterium.Journal of natural products, , 07-27, Volume: 81, Issue:7, 2018
Grassystatins D-F, Potent Aspartic Protease Inhibitors from Marine Cyanobacteria as Potential Antimetastatic Agents Targeting Invasive Breast Cancer.Journal of natural products, , 11-22, Volume: 80, Issue:11, 2017
Tasiamide F, a potent inhibitor of cathepsins D and E from a marine cyanobacterium.Bioorganic & medicinal chemistry, , 08-01, Volume: 24, Issue:15, 2016
Structure-based optimization of non-peptidic Cathepsin D inhibitors.Bioorganic & medicinal chemistry letters, , Sep-01, Volume: 24, Issue:17, 2014
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
Identification of 3-acetyl-2-aminoquinolin-4-one as a novel, nonpeptidic scaffold for specific calpain inhibitory activity.Journal of medicinal chemistry, , May-14, Volume: 52, Issue:9, 2009
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
Identification of acridinyl hydrazides as potent aspartic protease inhibitors.Bioorganic & medicinal chemistry letters, , May-01, Volume: 18, Issue:9, 2008
Synthesis of gallic acid based naphthophenone fatty acid amides as cathepsin D inhibitors.Bioorganic & medicinal chemistry letters, , Sep-01, Volume: 16, Issue:17, 2006
Protease inhibitors: current status and future prospects.Journal of medicinal chemistry, , Feb-10, Volume: 43, Issue:3, 2000
Synthesis and structure activity relationships of novel small molecule cathepsin D inhibitors.Bioorganic & medicinal chemistry letters, , Sep-06, Volume: 9, Issue:17, 1999
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
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
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
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
Grassystatins D-F, Potent Aspartic Protease Inhibitors from Marine Cyanobacteria as Potential Antimetastatic Agents Targeting Invasive Breast Cancer.Journal of natural products, , 11-22, Volume: 80, Issue:11, 2017
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
Total synthesis of grassystatin A, a probe for cathepsin E function.Bioorganic & medicinal chemistry, , Aug-01, Volume: 20, Issue:15, 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
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
Enables
This protein enables 5 target(s):
| Target | Category | Definition |
|---|
| cysteine-type endopeptidase activity | molecular function | Catalysis of the hydrolysis of internal, alpha-peptide bonds in a polypeptide chain by a mechanism in which the sulfhydryl group of a cysteine residue at the active center acts as a nucleophile. [GOC:mah, https://www.ebi.ac.uk/merops/about/glossary.shtml#CATTYPE, https://www.ebi.ac.uk/merops/about/glossary.shtml#ENDOPEPTIDASE] |
| 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] |
| aspartic-type peptidase activity | molecular function | Catalysis of the hydrolysis of 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. [GOC:mah, https://www.ebi.ac.uk/merops/about/glossary.shtml#CATTYPE] |
| 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] |
Located In
This protein is located in 14 target(s):
| Target | Category | Definition |
|---|
| extracellular region | cellular component | The space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane. This term covers the host cell environment outside an intracellular parasite. [GOC:go_curators] |
| extracellular space | cellular component | That part of a multicellular organism outside the cells proper, usually taken to be outside the plasma membranes, and occupied by fluid. [ISBN:0198547684] |
| 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] |
| lysosomal membrane | cellular component | The lipid bilayer surrounding the lysosome and separating its contents from the cell cytoplasm. [GOC:ai] |
| endosome membrane | cellular component | The lipid bilayer surrounding an endosome. [GOC:mah] |
| endosome lumen | cellular component | The volume enclosed by the membrane of an endosome. [GOC:mah] |
| specific granule lumen | cellular component | The volume enclosed by the membrane of a specific granule, a granule with a membranous, tubular internal structure, found primarily in mature neutrophil cells. Most are released into the extracellular fluid. Specific granules contain lactoferrin, lysozyme, vitamin B12 binding protein and elastase. [GOC:bf, PMID:7334549] |
| melanosome | cellular component | A tissue-specific, membrane-bounded cytoplasmic organelle within which melanin pigments are synthesized and stored. Melanosomes are synthesized in melanocyte cells. [GOC:jl, PMID:11584301] |
| lysosomal lumen | cellular component | The volume enclosed within the lysosomal membrane. [GOC:jl, PMID:15213228] |
| 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] |
| collagen-containing extracellular matrix | cellular component | An extracellular matrix consisting mainly of proteins (especially collagen) and glycosaminoglycans (mostly as proteoglycans) that provides not only essential physical scaffolding for the cellular constituents but can also initiate crucial biochemical and biomechanical cues required for tissue morphogenesis, differentiation and homeostasis. The components are secreted by cells in the vicinity and form a sheet underlying or overlying cells such as endothelial and epithelial cells. [GOC:BHF, GOC:rph, PMID:21123617] |
| extracellular exosome | cellular component | A vesicle that is released into the extracellular region by fusion of the limiting endosomal membrane of a multivesicular body with the plasma membrane. Extracellular exosomes, also simply called exosomes, have a diameter of about 40-100 nm. [GOC:BHF, GOC:mah, GOC:vesicles, PMID:15908444, PMID:17641064, PMID:19442504, PMID:19498381, PMID:22418571, PMID:24009894] |
| tertiary granule lumen | cellular component | Any membrane-enclosed lumen that is part of a tertiary granule. [GO_REF:0000064, GOC:TermGenie, PMID:23650620] |
| ficolin-1-rich granule lumen | cellular component | Any membrane-enclosed lumen that is part of a ficolin-1-rich granule. [GO_REF:0000064, GOC:TermGenie, PMID:23650620] |
Involved In
This protein is involved in 9 target(s):
| Target | Category | Definition |
|---|
| autophagosome assembly | biological process | The formation of a double membrane-bounded structure, the autophagosome, that occurs when a specialized membrane sac, called the isolation membrane, starts to enclose a portion of the cytoplasm. [GOC:autophagy, PMID:9412464] |
| proteolysis | biological process | The hydrolysis of proteins into smaller polypeptides and/or amino acids by cleavage of their peptide bonds. [GOC:bf, GOC:mah] |
| antigen processing and presentation of exogenous peptide antigen via MHC class II | biological process | The process in which an antigen-presenting cell expresses a peptide antigen of exogenous origin on its cell surface in association with an MHC class II protein complex. The peptide antigen is typically, but not always, processed from a whole protein. [GOC:add, ISBN:0781735149, PMID:15771591] |
| insulin receptor recycling | biological process | The process that results in the return of an insulin receptor to an active state at the plasma membrane. An active state is when the receptor is ready to receive an insulin signal. Internalized insulin receptors can be recycled to the plasma membrane or sorted to lysosomes for protein degradation. [GOC:bf, GOC:signaling, PMID:3907718] |
| lipoprotein catabolic process | biological process | The chemical reactions and pathways resulting in the breakdown of any conjugated, water-soluble protein in which the covalently attached nonprotein group consists of a lipid or lipids. [ISBN:0198506732] |
| positive regulation of apoptotic process | biological process | Any process that activates or increases the frequency, rate or extent of cell death by apoptotic process. [GOC:jl, GOC:mtg_apoptosis] |
| positive regulation of cysteine-type endopeptidase activity involved in apoptotic process | biological process | Any process that activates or increases the activity of a cysteine-type endopeptidase involved in the apoptotic process. [GOC:jl, GOC:mtg_apoptosis] |
| regulation of establishment of protein localization | biological process | Any process that modulates the frequency, rate or extent of the directed movement of a protein to a specific location. [GOC:BHF, GOC:mah] |
| insulin catabolic process | biological process | The chemical reactions and pathways resulting in the breakdown of insulin. [GOC:TermGenie] |