Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTQAJF1)

• DTT Name: Cathepsin G (CTSG)
• Synonyms: CG
• Gene Name: CTSG
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Peptidase
• UniProt ID: CATG_HUMAN
• TTD ID: T86385
• EC Number: EC 3.4.21.20
• Sequence:
  MQPLLLLLAFLLPTGAEAGEIIGGRESRPHSRPYMAYLQIQSPAGQSRCGGFLVREDFVL
  TAAHCWGSNINVTLGAHNIQRRENTQQHITARRAIRHPQYNQRTIQNDIMLLQLSRRVRR
  NRNVNPVALPRAQEGLRPGTLCTVAGWGRVSMRRGTDTLREVQLRVQRDRQCLRIFGSYD
  PRRQICVGDRRERKAAFKGDSGGPLLCNNVAHGIVSYGKSSGVPPEVFTRVSSFLPWIRT
  TMRSFKLLDQMETPL
• Function: Cleaves complement C3. Has antibacterial activity against the Gram-negative bacterium P. aeruginosa, antibacterial activity is inhibited by LPS from P. aeruginosa, Z-Gly-Leu-Phe-CH2Cl and phenylmethylsulfonyl fluoride. Serine protease with trypsin- and chymotrypsin-like specificity.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Lysosome (hsa04142)
  Renin-angiotensin system (hsa04614)
  Amoebiasis (hsa05146)
  Systemic lupus erythematosus (hsa05322)
• Reactome Pathway:
  Activation of Matrix Metalloproteinases (R-HSA-1592389)
  Metabolism of Angiotensinogen to Angiotensins (R-HSA-2022377)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
  Degradation of the extracellular matrix (R-HSA-1474228)

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
JNJ-10311795	DM7OTQS	Chronic obstructive pulmonary disease	CA22	Phase 2	[1]

9 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Peptide analog 55	DMVLP8H	N. A.	N. A.	Patented	[2]
Peptide analog 56	DMBCFJU	N. A.	N. A.	Patented	[2]
Peptide analog 57	DM6IQWE	N. A.	N. A.	Patented	[2]
Peptide analog 58	DM7X62M	N. A.	N. A.	Patented	[2]
Peptide analog 59	DMZAMNX	N. A.	N. A.	Patented	[2]
Peptide analog 60	DMMSTNA	N. A.	N. A.	Patented	[2]
Peptide analog 61	DM45JMT	N. A.	N. A.	Patented	[2]
Peptide analog 62	DM28NK0	N. A.	N. A.	Patented	[2]
Peptide analog 70	DMN43Q5	N. A.	N. A.	Patented	[2]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aloxistatin	DMGW07M	Neurological disorder	6B60	Discontinued in Phase 3	[3]
Dermolastin	DM6WSU2	Atopic dermatitis	EA80	Discontinued in Phase 2	[4]

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1,3-Dibenzyl-[1,3]diazetidine-2,4-dione	DM8NARQ	Discovery agent	N.A.	Investigative	[5]
Bis-Napthyl Beta-Ketophosphonic Acid	DM0K6QH	Discovery agent	N.A.	Investigative	[6]
PMID22595175C4g	DM9SLUK	Discovery agent	N.A.	Investigative	[7]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Chronic obstructive pulmonary disease	CA23	Lung tissue	8.23E-01	0.23	0.26
Chronic obstructive pulmonary disease	CA23	Small airway epithelium	5.14E-01	0.05	0.19
Asthma	CA23	Nasal and bronchial airway	3.71E-02	0.08	0.16
Atopic dermatitis	EA90	Skin	1.39E-04	-0.87	-1.12
Multiple myeloma	2C82	Bone marrow	1.80E-01	-0.43	-1.03

References

• [1] Discovery of potent, selective, orally active, nonpeptide inhibitors of human mast cell chymase. J Med Chem. 2007 Apr 19;50(8):1727-30.
• [2] Neutrophil elastase inhibitors: a patent review and potential applications for inflammatory lung diseases (2010 - 2014).Expert Opin Ther Pat. 2015;25(10):1145-58.
• [3] Inhibition of the activation of multiple serine proteases with a cathepsin C inhibitor requires sustained exposure to prevent pro-enzyme processing. J Biol Chem. 2007 Jul 20;282(29):20836-46.
• [4] Arriva-ProMetic recombinant alpha 1-antitrypsin (rAAT) moves into the clinic for dermatology applications. ProMetic Life Sciences. 2009.
• [5] Inhibition of serine proteases: activity of 1,3-diazetidine-2,4-diones. Bioorg Med Chem Lett. 2001 Jul 9;11(13):1691-4.
• [6] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [7] N-Acyl and N-sulfonyloxazolidine-2,4-diones are pseudo-irreversible inhibitors of serine proteases. Bioorg Med Chem Lett. 2012 Jun 15;22(12):3993-7.