Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTHXFA1)

• DTT Name: C5a anaphylatoxin chemotactic receptor (C5AR1)
• Synonyms: CD88; C5aR; C5a-R; C5a anaphylatoxin chemotactic receptor 1; C5R1
• Gene Name: C5AR1
• DTT Type: Clinical trial target; [1]
• Related Disease: Vasculitis [ICD-11: 4A44]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: C5AR1_HUMAN
• TTD ID: T15439
• Sequence:
  MDSFNYTTPDYGHYDDKDTLDLNTPVDKTSNTLRVPDILALVIFAVVFLVGVLGNALVVW
  VTAFEAKRTINAIWFLNLAVADFLSCLALPILFTSIVQHHHWPFGGAACSILPSLILLNM
  YASILLLATISADRFLLVFKPIWCQNFRGAGLAWIACAVAWGLALLLTIPSFLYRVVREE
  YFPPKVLCGVDYSHDKRRERAVAIVRLVLGFLWPLLTLTICYTFILLRTWSRRATRSTKT
  LKVVVAVVASFFIFWLPYQVTGIMMSFLEPSSPTFLLLKKLDSLCVSFAYINCCINPIIY
  VVAGQGFQGRLRKSLPSLLRNVLTEESVVRESKSFTRSTVDTMAQKTQAV
• Function: The ligand interacts with at least two sites on the receptor: a high-affinity site on the extracellular N-terminus, and a second site in the transmembrane region which activates downstream signaling events. Receptor activation stimulates chemotaxis, granule enzyme release, intracellular calcium release and superoxide anion production. Receptor for the chemotactic and inflammatory peptide anaphylatoxin C5a.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Complement and coagulation cascades (hsa04610)
  Staphylococcus aureus infection (hsa05150)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CCX-168	DM5LQHB	Anca-associated vasculitis	4A44.A	Phase 3	[1]
PMX-53	DMZUAJ4	Atopic dermatitis	EA80	Phase 2	[2]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NN8209	DM2TDE7	Rheumatoid arthritis	FA20	Discontinued in Phase 2	[3]
NN8210	DM8Z5VH	Rheumatoid arthritis	FA20	Discontinued in Phase 1	[3]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMX205	DMMXR3L	Central nervous system disease	8A04-8D87	Preclinical	[4]

4 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
C5aR pepducins	DMEK4HZ	Inflammation	1A00-CA43.1	Investigative	[5]
NDT9520492	DMFKX7Z	Discovery agent	N.A.	Investigative	[6]
RPR121154	DM9DXHM	Discovery agent	N.A.	Investigative	[5]
W54011	DMQI7BA	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
Rheumatoid arthritis	FA20	Synovial tissue	3.99E-01	1.19	0.77
Atopic dermatitis	EA90	Skin	2.34E-02	0.29	0.87

References

• [1] Clinical pipeline report, company report or official report of ChemoCentryx.
• [2] Company report (Arana Therapeutics)
• [3] Complement in immune and inflammatory disorders: therapeutic interventions. J Immunol. 2013 Apr 15;190(8):3839-47.
• [4] Development and validation of a LC-MS/MS assay for pharmacokinetic studies of complement C5a receptor antagonists PMX53 and PMX205 in mice. Sci Rep. 2018 May 25;8(1):8101.
• [5] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 32).
• [6] Molecular characterization of the gerbil C5a receptor and identification of a transmembrane domain V amino acid that is crucial for small molecule ... J Biol Chem. 2005 Dec 9;280(49):40617-23.
• [7] Identification of a potent and orally active non-peptide C5a receptor antagonist. J Biol Chem. 2002 Dec 20;277(51):49403-7.