Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT7LRQH)

• DTT Name: Complement C1s component (C1S)
• Synonyms: Complement component 1 subcomponent s; Complement C1s subcomponent; C1-esterase; C1 esterase
• Gene Name: C1S
• DTT Type: Successful target; [1]
• BioChemical Class: Peptidase
• UniProt ID: C1S_HUMAN
• TTD ID: T76024
• EC Number: EC 3.4.21.42
• Sequence:
  MWCIVLFSLLAWVYAEPTMYGEILSPNYPQAYPSEVEKSWDIEVPEGYGIHLYFTHLDIE
  LSENCAYDSVQIISGDTEEGRLCGQRSSNNPHSPIVEEFQVPYNKLQVIFKSDFSNEERF
  TGFAAYYVATDINECTDFVDVPCSHFCNNFIGGYFCSCPPEYFLHDDMKNCGVNCSGDVF
  TALIGEIASPNYPKPYPENSRCEYQIRLEKGFQVVVTLRREDFDVEAADSAGNCLDSLVF
  VAGDRQFGPYCGHGFPGPLNIETKSNALDIIFQTDLTGQKKGWKLRYHGDPMPCPKEDTP
  NSVWEPAKAKYVFRDVVQITCLDGFEVVEGRVGATSFYSTCQSNGKWSNSKLKCQPVDCG
  IPESIENGKVEDPESTLFGSVIRYTCEEPYYYMENGGGGEYHCAGNGSWVNEVLGPELPK
  CVPVCGVPREPFEEKQRIIGGSDADIKNFPWQVFFDNPWAGGALINEYWVLTAAHVVEGN
  REPTMYVGSTSVQTSRLAKSKMLTPEHVFIHPGWKLLEVPEGRTNFDNDIALVRLKDPVK
  MGPTVSPICLPGTSSDYNLMDGDLGLISGWGRTEKRDRAVRLKAARLPVAPLRKCKEVKV
  EKPTADAEAYVFTPNMICAGGEKGMDSCKGDSGGAFAVQDPNDKTKFYAAGLVSWGPQCG
  TYGLYTRVKNYVDWIMKTMQENSTPRED
• Function: C1r activates C1s so that it can, in turn, activate C2 and C4. C1s B chain is a serine protease that combines with C1q and C1r to form C1, the first component of the classical pathway of the complement system.
• KEGG Pathway:
  Complement and coagulation cascades (hsa04610)
  Pertussis (hsa05133)
  Staphylococcus aureus infection (hsa05150)
  Systemic lupus erythematosus (hsa05322)
• Reactome Pathway:
  Classical antibody-mediated complement activation (R-HSA-173623)
  Regulation of Complement cascade (R-HSA-977606)
  Initial triggering of complement (R-HSA-166663)

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cinryze	DMVIKJZ	Hereditary angioedema	4A00.14	Approved	[1]
Sutimlimab	DMY7WH1	Cold type autoimmune haemolytic anemia	3A20.1	Approved	[2]

5 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SAR445088	DMQV3IM	Chronic inflammatory demyelinating polyneuropathy	8C01.3	Phase 2	[3]
ANX005	DMAESIY	Neurodegenerative disorder	8A20-8A23	Phase 1	[4]
SHP616	DMO0CA8	Neuromyelitis optica	8A43	Phase 1	[5]
TNT009	DMSKF29	Bullous pemphigoid	EB41.0	Phase 1	[5]
TS01	DMNTVUK	Stroke	8B20	Phase 1	[6]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fucose	DMAHMSV	N. A.	N. A.	Investigative	[7]
PMID16460935C28	DM8BKI4	Discovery agent	N.A.	Investigative	[8]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Thrombocytopenia	3B64	Whole blood	5.50E-01	1.09	0.91

References

• [1] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [2] Antibodies to watch in 2020. MAbs. Jan-Dec 2020;12(1):1703531.
• [3] First-in-human study with SAR445088: A novel selective classical complement pathway inhibitor. Clin Transl Sci. 2023 Apr;16(4):673-685.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [7] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [8] A novel series of arylsulfonylthiophene-2-carboxamidine inhibitors of the complement component C1s. Bioorg Med Chem Lett. 2006 Apr 15;16(8):2200-4.