Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTPT2QI)

• DTT Name: Cathepsin D (CTSD)
• Synonyms: CPSD; CD
• Gene Name: CTSD
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Peptidase
• UniProt ID: CATD_HUMAN
• TTD ID: T67102
• EC Number: EC 3.4.23.5
• Sequence:
  MQPSSLLPLALCLLAAPASALVRIPLHKFTSIRRTMSEVGGSVEDLIAKGPVSKYSQAVP
  AVTEGPIPEVLKNYMDAQYYGEIGIGTPPQCFTVVFDTGSSNLWVPSIHCKLLDIACWIH
  HKYNSDKSSTYVKNGTSFDIHYGSGSLSGYLSQDTVSVPCQSASSASALGGVKVERQVFG
  EATKQPGITFIAAKFDGILGMAYPRISVNNVLPVFDNLMQQKLVDQNIFSFYLSRDPDAQ
  PGGELMLGGTDSKYYKGSLSYLNVTRKAYWQVHLDQVEVASGLTLCKEGCEAIVDTGTSL
  MVGPVDEVRELQKAIGAVPLIQGEYMIPCEKVSTLPAITLKLGGKGYKLSPEDYTLKVSQ
  AGKTLCLSGFMGMDIPPPSGPLWILGDVFIGRYYTVFDRDNNRVGFAEAARL
• Function: Plays a role in APP processing following cleavage and activation by ADAM30 which leads to APP degradation. Involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer disease. Acid protease active in intracellular protein breakdown.
• KEGG Pathway:
  Sphingolipid signaling pathway (hsa04071)
  Lysosome (hsa04142)
  Tuberculosis (hsa05152)
• Reactome Pathway:
  Metabolism of Angiotensinogen to Angiotensins (R-HSA-2022377)
  MHC class II antigen presentation (R-HSA-2132295)
  Collagen degradation (R-HSA-1442490)
• BioCyc Pathway: MetaCyc:HS04183-MON

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID10498202C1	DMXE0F2	Multiple sclerosis	8A40	Clinical trial	[1]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CI-992	DMBHYIJ	Hypertension	BA00-BA04	Terminated	[2]

9 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1h-Benoximidazole-2-Carboxylic Acid	DMNZAVE	Discovery agent	N.A.	Investigative	[3]
Alpha-D-Mannose	DMF5DLW	Discovery agent	N.A.	Investigative	[3]
Carbocyclic Peptidomimetic	DM87SOX	Discovery agent	N.A.	Investigative	[4]
Grassystatin a	DM1PWX2	Discovery agent	N.A.	Investigative	[5]
GRL-7234	DMR93MK	Discovery agent	N.A.	Investigative	[6]
KNI-10006	DMMISH6	Discovery agent	N.A.	Investigative	[7]
N-Aminoethylmorpholine	DMWXBYC	Discovery agent	N.A.	Investigative	[3]
PMID8410973C3	DM6J5KY	Discovery agent	N.A.	Investigative	[8]
S-Methylcysteine	DMAMRKS	Discovery agent	N.A.	Investigative	[3]

References

• [1] Synthesis and structure activity relationships of novel small molecule cathepsin D inhibitors. Bioorg Med Chem Lett. 1999 Sep 6;9(17):2531-6.
• [2] Structure-activity relationships of a series of 2-amino-4-thiazole-containing renin inhibitors. J Med Chem. 1992 Jul 10;35(14):2562-72.
• [3] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [4] Structure-based design, synthesis, and memapsin 2 (BACE) inhibitory activity of carbocyclic and heterocyclic peptidomimetics. J Med Chem. 2005 Aug 11;48(16):5175-90.
• [5] Grassystatins A-C from marine cyanobacteria, potent cathepsin E inhibitors that reduce antigen presentation. J Med Chem. 2009 Sep 24;52(18):5732-47.
• [6] Design, synthesis, and X-ray structure of potent memapsin 2 (beta-secretase) inhibitors with isophthalamide derivatives as the P2-P3-ligands. J Med Chem. 2007 May 17;50(10):2399-407.
• [7] alpha-Substituted norstatines as the transition-state mimic in inhibitors of multiple digestive vacuole malaria aspartic proteases. Bioorg Med Chem. 2009 Aug 15;17(16):5933-49.
• [8] Specificity in the binding of inhibitors to the active site of human/primate aspartic proteinases: analysis of P2-P1-P1'-P2' variation. J Med Chem. 1993 Sep 3;36(18):2614-20.