C5AR1

Summary

C5AR1 (complement C5a receptor 1, HGNC:1338) is a protein-coding gene on chromosome 19q13.32, encoding C5a anaphylatoxin chemotactic receptor 1 (P21730). Receptor for the chemotactic and inflammatory peptide anaphylatoxin C5a, stimulating chemotaxis, granule enzyme release, intracellular calcium release and superoxide anion production.

Enables G protein-coupled receptor activity and complement component C5a receptor activity. Involved in several processes, including complement component C5a signaling pathway; mRNA transcription by RNA polymerase II; and positive regulation of ERK1 and ERK2 cascade. Located in apical part of cell and basolateral plasma membrane. Biomarker of Alzheimer’s disease; asthma; chronic obstructive pulmonary disease; rhinitis; and severe acute respiratory syndrome.

Source: NCBI Gene 728 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 70 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001736

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1338
Approved symbol	C5AR1
Name	complement C5a receptor 1
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	C5A, C5AR, CD88
Ensembl gene	ENSG00000197405
Ensembl biotype	protein_coding
OMIM	113995
Entrez	728

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000355085, ENST00000594787, ENST00000595501

RefSeq mRNA: 1 — MANE Select: NM_001736 NM_001736

CCDS: CCDS33063

Canonical transcript exons

ENST00000355085 — 2 exons

Exon	Start	End
ENSE00001292786	47309861	47309898
ENSE00001425109	47319781	47322066

Expression profiles

Bgee: expression breadth ubiquitous, 215 present calls, max score 98.45.

FANTOM5 (CAGE): breadth broad, TPM avg 36.0700 / max 3866.5664, expressed in 542 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176658	34.8841	456
176664	0.4588	107
176665	0.2014	77
176657	0.1619	75
176656	0.1093	31
176662	0.0912	49
176663	0.0830	36
176661	0.0803	46

Top tissues by expression

273 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	98.45	gold quality
monocyte	CL:0000576	98.25	gold quality
mononuclear cell	CL:0000842	98.09	gold quality
leukocyte	CL:0000738	98.04	gold quality
bone marrow	UBERON:0002371	95.76	gold quality
granulocyte	CL:0000094	95.75	gold quality
bone marrow cell	CL:0002092	94.76	gold quality
pituitary gland	UBERON:0000007	94.48	gold quality
right lung	UBERON:0002167	94.39	gold quality
adenohypophysis	UBERON:0002196	94.24	gold quality
periodontal ligament	UBERON:0008266	93.60	gold quality
upper lobe of left lung	UBERON:0008952	92.48	gold quality
right uterine tube	UBERON:0001302	92.07	gold quality
trabecular bone tissue	UBERON:0002483	92.05	gold quality
gall bladder	UBERON:0002110	91.99	gold quality
upper lobe of lung	UBERON:0008948	91.98	gold quality
lower lobe of lung	UBERON:0008949	90.69	gold quality
spleen	UBERON:0002106	90.51	gold quality
epithelium of bronchus	UBERON:0002031	89.35	gold quality
bronchial epithelial cell	CL:0002328	89.29	gold quality
descending thoracic aorta	UBERON:0002345	89.20	gold quality
left uterine tube	UBERON:0001303	89.16	gold quality
thoracic aorta	UBERON:0001515	88.76	gold quality
ascending aorta	UBERON:0001496	88.74	gold quality
bronchus	UBERON:0002185	88.74	gold quality
lung	UBERON:0002048	88.58	gold quality
omental fat pad	UBERON:0010414	88.39	gold quality
vermiform appendix	UBERON:0001154	88.35	gold quality
peritoneum	UBERON:0002358	88.31	gold quality
adipose tissue of abdominal region	UBERON:0007808	87.38	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	1023.27
E-HCAD-15	yes	1002.95
E-MTAB-8498	yes	510.19
E-CURD-122	yes	78.93
E-HCAD-1	yes	76.79
E-ANND-3	yes	43.82
E-MTAB-6678	yes	43.76
E-GEOD-84465	yes	38.95
E-MTAB-9467	yes	22.88
E-MTAB-9221	yes	22.41
E-HCAD-10	yes	15.21
E-CURD-88	yes	13.27
E-MTAB-9801	yes	9.74
E-GEOD-130148	yes	6.12
E-MTAB-6379	no	3.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

86 targeting C5AR1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6733-5P	99.74	67.94	2759

Literature-anchored findings (GeneRIF, showing 40)

• The C5a receptor residue Asp-282 near the extracellular face of transmembrane domain VII, is a component of the ligand-binding site responsible for C5a receptor activation. (PMID:11705397)
• C5a induced PAI-1 production in human mast cells and basophils and, in HMC-1 cells, was mediated by C5aR. (PMID:12091343)
• complement factor 5a receptor has multiple activated conformations (PMID:12453150)
• role of phosphorylation of key serine residues for internalization via a beta-arrestin, dynamin, and clathrin-dependent pathway (PMID:12464600)
• results indicated that the conversion of the RP S19 dimer from agonist to antagonist of C5a receptor is attributed to the IAGQVAAANKK moiety between Ile134 and Lys144 (PMID:12651630)
• C5aR may mediate abnormal calcium signaling when expressed in hippocampal and cortical neurons of Alzheimer’s disease and vascular dementia patients. (PMID:12759460)
• Within the C5a molecule three different discontinuous regions representing N-terminal, middle, and C-terminal regions of C5a exist and interact with the C5a receptor, as proposed by a three-site binding model. (PMID:12794141)
• A mutant of this protein is a potent antagonist for the human and mouse C5a receptor (CD88). (PMID:14570896)
• determination of whether the levels of complement factors C3a, C4a, and C5a are elevated at the site of inflammation in chronic obstructive pulmonary disease and in asthma (PMID:15039137)
• A synthetic peptide complementary to amino acids 37-53 of C5a-anaphylatoxin binds to and inactivates C5a, inhibits induction of intracellular Ca2+ influx in neutrophils, and prevents C5a-mediated rapid lethal shock in a rat model. (PMID:15128829)
• Human C5aR antagonist treatment reduced total hepatic reperfusion injury-induced mortality in rats. (PMID:15158333)
• the C5a chemotactic cofactor function of vitamin D-binding protein requires its 20-amino-acid sequence (residues 130-149, 5’-EAFRKDPKEYANQFMWEYST-3’) in domain I (PMID:15485893)
• analysis of binding mode for C5a to the C5aR (PMID:15550394)
• C5a receptor plays a role in glomerular physiology (PMID:15944400)
• the anaphylatoxin C5a potentiates cysLT production in human lung tissues and contributes to allergic inflammation in disorders such as asthma. (PMID:16301808)
• C5aR signaling at the dendritic cell/T cell interface during allergen priming provides protection against inflammatory responses to harmless antigens at the mucosal surface (PMID:16511606)
• C5aR is expressed on plasmacytoid dendritic cells. (PMID:16778800)
• C5a and its receptor have roles in PAI-1 production (PMID:16879222)
• analysis of the structural constraint for C5a docking with the complement factor 5a (C5a) receptor N terminus (PMID:17023413)
• C5L2 is a highly regulated scavenger receptor for C5a and C5a-des-Arg(74) (PMID:17068344)
• arboxyl-terminal tail acts together with the intracellular loops to generate a specificity filter for ths and other receptor-G protein interactions that functions primarily to restrict access of incorrect G proteins to the receptor. (PMID:17090530)
• Functional maps of the intracellular surface of thsi protein, and further, any G protein-coupled receptor to date. (PMID:17135254)
• The RP S19 dimer inhibits C5a-induced neutrophil migration and promotes apoptosis of neutrophils via the C5a receptor. (PMID:17199736)
• endothelial cells and subendothelial smooth muscle cells express both C3aR and C5aR (PMID:17234193)
• PLD control over expression of the Mac-1 activation epitope is critical for neutrophil migration to fMLP but not C5a. (PMID:17724165)
• A common genetic variant at the TRAF1-C5 locus on chromosome 9 is associated with an increased risk of anti-CCP-positive rheumatoid arthritis. (PMID:17804836)
• Our data establish a link between C5a and the gp130 receptor cytokine family with possible implications for the pathology of inflammatory diseases. (PMID:18187666)
• on the basis of the location of C3aR and C5aR, C5aR may play a role in activation of inflammatory cells, whereas C3aR may mediate mucus secretion and mucosal swelling in allergic nasal mucosa, especially severe persistent allergic nasal mucosa (PMID:18538384)
• C5aR plays an important role in mediating acute kidney allograft rejection (PMID:18753257)
• in the case of C5aR, the stimulation and phosphorylation of one monomer is enough to lead to dimer internalization. (PMID:18772131)
• Significantly more transcripts encoding alternative pathway components factor B, C3 and properdin, and C3a receptor and C5a receptor were detected in grade 3 versus grade 0 or 1 biopsies of human cardiac allografts. (PMID:19005416)
• the complex of CHIPS and a sulfated C5aR N-terminal peptide reveals the precise binding motif as well as the distinct roles of sulfated tyrosine residues sY11 and sY14. (PMID:19251703)
• C5a caused dysregulated induction of cytokines in Plasmodium falciparum infected monocytes; C5a levels were significantly elevated in women with placental malaria in Kenya. (PMID:19308263)
• C5a recapitulates impaired peripheral blood neutrophil phagocytosis and significantly down-regulates neutrophil CD88 (complement component 5a receptor) expression in vitro (PMID:19324972)
• in apoptosis-initiated cells, the ligand-dependent C5aR-mediated dual signal affects the fate of cells, either apoptosis execution or survival, through regulation of RGS3 gene expression and subsequent modulation of ERK signal. (PMID:19333232)
• C5a has been found to be a significant pathogenic driver in a number of immuno-inflammatory diseases, making C5a inhibition an attractive therapeutic strategy. (PMID:19464229)
• The aim of this study is to investigate C5a receptor (C5aR) gene polymorphism in patients with familial Mediterranean fever and its relation to the main features of the disease. (PMID:19657723)
• expression profiles of CRegs and CD88 on leukocytes are specifically altered after polytrauma in humans, indicating a trauma-induced “complementopathy (PMID:19864971)
• Data show that C5L2 is predominantly intracellular, while C5aR is expressed on the plasma membrane, and that internalized C5aR following ligand binding is co-localized with both C5L2 and beta-arrestin. (PMID:20044484)
• Data show that when a Gi/PI3K pathway is partially blocked, C5a receptors stimulate an alternative p38MAPK pathway. (PMID:20473571)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	c5ar1	ENSDARG00000040319
mus_musculus	C5ar1	ENSMUSG00000049130
rattus_norvegicus		ENSRNOG00000074439

Paralogs (8): C5AR2 (ENSG00000134830), GPR32 (ENSG00000142511), FPR2 (ENSG00000171049), FPR1 (ENSG00000171051), C3AR1 (ENSG00000171860), CMKLR1 (ENSG00000174600), FPR3 (ENSG00000187474), GPR33 (ENSG00000214943)

Protein

Protein identifiers

C5a anaphylatoxin chemotactic receptor 1 — P21730 (reviewed: P21730)

Alternative names: C5a anaphylatoxin chemotactic receptor

All UniProt accessions (2): P21730, M0QZK7

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for the chemotactic and inflammatory peptide anaphylatoxin C5a, stimulating chemotaxis, granule enzyme release, intracellular calcium release and superoxide anion production. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase. C5AR1 is coupled to G(i)/G(o) (GNAI1 or GNAO1) G alpha proteins and mediates inhibition of adenylate cyclase. 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.

Subunit / interactions. Homodimer. May also form higher-order oligomers. Interacts (when phosphorylated) with ARRB1 and ARRB2; the interaction is associated with internalization of the receptor and short-term desensitization to the ligand. (Microbial infection) Interacts (via N-terminal domain) with S.aureus chemotaxis inhibitory protein (CHIPS); the interaction blocks the receptor and may thus inhibit the immune response.

Subcellular location. Cell membrane. Cytoplasmic vesicle.

Post-translational modifications. Phosphorylation of the P-X-P-P motif by GRK2 or GRK3 in response to C5a binding promotes association with beta-arrestin (ARRB1 and/or ARRB2), resulting in internalization of the receptor and short-term desensitization to the ligand. Sulfation plays a critical role in the association of C5aR with C5a, but no significant role in the ability of the receptor to transduce a signal and mobilize calcium in response to a small a small peptide agonist. Sulfation at Tyr-14 is important for CHIPS binding.

Activity regulation. Activated by peptide agonist PMX53. Specifically inhibited by small-molecule antagonist NDT9513727.

Domain organisation. The P-X-P-P motif is phosphorylated by GRK2 or GRK3 in response to C5a binding, promoting. association with beta-arrestin (ARRB1 and/or ARRB2).

Similarity. Belongs to the G-protein coupled receptor 1 family.

RefSeq proteins (1): NP_001727* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000826	Formyl_rcpt-rel	Family
IPR002234	Anphylx_rcpt_C3a/C5a1-2	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (87 total): mutagenesis site 27, helix 16, modified residue 11, topological domain 8, transmembrane region 7, strand 6, turn 4, region of interest 2, sequence variant 2, chain 1, short sequence motif 1, glycosylation site 1, disulfide bond 1

Structure

Experimental structures (PDB)

19 structures.

PDB	Method	Resolution (Å)
6C1R	X-RAY DIFFRACTION	2.2
5O9H	X-RAY DIFFRACTION	2.7
7Y67	ELECTRON MICROSCOPY	2.8
6C1Q	X-RAY DIFFRACTION	2.9
7Y64	ELECTRON MICROSCOPY	2.9
7Y66	ELECTRON MICROSCOPY	2.9
8HK5	ELECTRON MICROSCOPY	3
9KUG	ELECTRON MICROSCOPY	3.07
9UMR	ELECTRON MICROSCOPY	3.15
7Y65	ELECTRON MICROSCOPY	3.2
9UMX	ELECTRON MICROSCOPY	3.2
8IA2	ELECTRON MICROSCOPY	3.21
8I0N	ELECTRON MICROSCOPY	3.26
8JZZ	ELECTRON MICROSCOPY	3.31
8GO8	ELECTRON MICROSCOPY	3.41
8JZP	ELECTRON MICROSCOPY	3.45
8I0Z	ELECTRON MICROSCOPY	4.33
8GOO	ELECTRON MICROSCOPY	4.4
2K3U	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21730-F1	85.57	0.67

Antibody-complex structures (SAbDab): 14 — 7Y64, 7Y65, 7Y66, 7Y67, 8GO8, 8GOO, 8I0N, 8I0Z, 8IA2, 8JZP, 8JZZ, 9KUG, 9UMR, 9UMX

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (11): 11, 14, 314, 317, 327, 332, 334, 336, 338, 339, 342

Disulfide bonds (1): 109–188

Glycosylation sites (1): 5

Mutagenesis-validated functional residues (27):

Position	Phenotype
2–30	strongly impairs c5a binding (45,000-fold).
2–22	impairs c5a binding. strongly impairs c5a binding; when associated with a-27.
10	strongly impairs c5a binding; when associated with a-15; a-16; a-18 and a-21 (pubmed:8182049). moderately impairs chips
11	weakly impairs chips binding. loss of chips binding; when associated with f-14.
12	moderately impairs chips binding.
14	weakly impairs chips binding (pubmed:15542591). strongly impairs chips binding (pubmed:21706042). loss of chips binding;
15	strongly impairs c5a binding; when associated with a-10; a-16; a-18 and a-21 (pubmed:8182049). moderately impairs chips
16	strongly impairs c5a binding; when associated with a-10; a-15; a-18 and a-21.
18	strongly impairs c5a binding; when associated with a-10; a-15; a-16 and a-21 (pubmed:8182049). impairs chips binding (pu
21	strongly impairs c5a binding; when associated with a-10; a-15; a-16 and a-18.
27	strongly impairs c5a binding; when associated with 2-d–l-22 del. decreased ability to activate g(i)/gnai1.
33	decreased ability to activate g(i)/gnai1.
34	decreased ability to activate g(i)/gnai1.
144	fails to homodimerize.
157	no effect on homodimer formation.
175	reduced activation by anaphylatoxin c5a.
180	decreased ability to activate g(i)/gnai1.
181	decreased ability to activate g(i)/gnai1.
182	decreased ability to activate g(i)/gnai1.
183	decreased ability to activate g(i)/gnai1.
191	reduced activation by anaphylatoxin c5a.
199	reduced activation by anaphylatoxin c5a.
199	impairs c5a binding (10-fold reduction) and c5a-induced 5-ht secretion.
221	no effect on homodimer formation.
258	decreased ability to activate g(i)/gnai1. reduced activation by anaphylatoxin c5a.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-418594	G alpha (i) signalling events
R-HSA-6798695	Neutrophil degranulation
R-HSA-977606	Regulation of Complement cascade
R-HSA-162582	Signal Transduction
R-HSA-166658	Complement cascade
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 354 (showing top): TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_COGNITION, MCLACHLAN_DENTAL_CARIES_UP, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOCC_SECRETORY_GRANULE, MODULE_64, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT, GOBP_GLIAL_CELL_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS

GO Biological Process (30): microglial cell activation (GO:0001774), complement receptor mediated signaling pathway (GO:0002430), chemotaxis (GO:0006935), inflammatory response (GO:0006954), immune response (GO:0006955), cellular defense response (GO:0006968), signal transduction (GO:0007165), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), positive regulation of cytosolic calcium ion concentration (GO:0007204), sensory perception of chemical stimulus (GO:0007606), positive regulation of vascular endothelial growth factor production (GO:0010575), positive regulation of macrophage chemotaxis (GO:0010759), neutrophil chemotaxis (GO:0030593), response to peptidoglycan (GO:0032494), complement component C5a signaling pathway (GO:0038178), mRNA transcription by RNA polymerase II (GO:0042789), positive regulation of angiogenesis (GO:0045766), astrocyte activation (GO:0048143), positive regulation of epithelial cell proliferation (GO:0050679), defense response to Gram-positive bacterium (GO:0050830), cognition (GO:0050890), positive regulation of ERK1 and ERK2 cascade (GO:0070374), positive regulation of neutrophil chemotaxis (GO:0090023), amyloid-beta clearance (GO:0097242), presynapse organization (GO:0099172), regulation of immune system process (GO:0002682), cell communication (GO:0007154), G protein-coupled receptor signaling pathway (GO:0007186), signaling (GO:0023052)

GO Molecular Function (3): complement component C5a receptor activity (GO:0004878), G protein-coupled receptor activity (GO:0004930), complement receptor activity (GO:0004875)

GO Cellular Component (6): plasma membrane (GO:0005886), basolateral plasma membrane (GO:0016323), secretory granule membrane (GO:0030667), apical part of cell (GO:0045177), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Innate Immune System	2
Signaling by GPCR	2
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1
Complement cascade	1
Immune System	1
Signal Transduction	1
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	3
glial cell activation	2
defense response	2
complement receptor mediated signaling pathway	2
transmembrane signaling receptor activity	2
cellular anatomical structure	2
leukocyte activation involved in inflammatory response	1
macrophage activation	1
immune response-activating cell surface receptor signaling pathway	1
response to chemical	1
taxis	1
immune system process	1
response to stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
phospholipase C activator activity	1
regulation of biological quality	1
sensory perception	1
positive regulation of cytokine production	1
vascular endothelial growth factor production	1
regulation of vascular endothelial growth factor production	1
positive regulation of leukocyte chemotaxis	1
regulation of macrophage chemotaxis	1
macrophage chemotaxis	1
regulation of granulocyte chemotaxis	1
positive regulation of macrophage migration	1
granulocyte chemotaxis	1
neutrophil migration	1
response to molecule of bacterial origin	1
response to nitrogen compound	1
response to oxygen-containing compound	1
transcription by RNA polymerase II	1
mRNA transcription	1
angiogenesis	1
regulation of angiogenesis	1

Protein interactions and networks

STRING

2000 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C5AR1	C5	P01031	998
C5AR1	RPS19	P39019	986
C5AR1	C4A	P01028	980
C5AR1	C3AR1	Q16581	970
C5AR1	C3	P01024	955
C5AR1	TLR2	O60603	903
C5AR1	CCR5	P51681	849
C5AR1	C1QA	P02745	783
C5AR1	C5AR2	Q9P296	775
C5AR1	MBL2	P11226	772
C5AR1	SERPING1	P05155	752
C5AR1	C4A	P01028	745
C5AR1	ITGAM	P11215	740
C5AR1	CR1	P17927	724
C5AR1	TNF	P01375	701

IntAct

14 interactions, top by confidence:

A	B	Type	Score
C5AR1	PTPN1	psi-mi:“MI:0914”(association)	0.530
C5AR1	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	C5AR1	psi-mi:“MI:0915”(physical association)	0.400
C5AR1	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	C5AR1	psi-mi:“MI:0915”(physical association)	0.400
C5AR1	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
C5AR1	TCAF2	psi-mi:“MI:0914”(association)	0.350
C5AR1	SLC12A8	psi-mi:“MI:0914”(association)	0.350
GNAI2	C5AR1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (155): GNAI2 (Co-localization), WAS (Two-hybrid), WAS (Reconstituted Complex), C5AR1 (Reconstituted Complex), WAS (Affinity Capture-Western), C5AR1 (Co-localization), C5 (Reconstituted Complex), GNAI2 (Co-purification), GNAI3 (Co-purification), TM9SF1 (Affinity Capture-MS), CHPT1 (Affinity Capture-MS), SLC35F1 (Affinity Capture-MS), RMND1 (Affinity Capture-MS), GOLPH3 (Affinity Capture-MS), SETX (Affinity Capture-MS)

ESM2 similar proteins: A4FUQ5, B9VR26, O08790, O35786, O70129, O75388, O88416, O88536, O88537, O97664, P0C7U4, P21462, P21730, P25089, P25090, P30992, P30993, P33766, P35343, P35407, P46090, P46091, P79175, P79176, P79177, P79178, P79188, P79189, P79190, P79191, P79234, P79235, P79236, P79237, P79240, P79241, P79242, P79243, P97468, P97520

Diamond homologs: A4FUQ5, B1PHQ8, B9VR26, O08565, O08790, O35210, O35786, O62747, O70129, O75388, O77590, O88416, O88536, O88537, O97571, O97664, P0C7U4, P0C7U5, P21462, P21730, P25025, P25089, P25090, P25095, P25104, P28646, P29089, P29754, P29755, P30555, P30556, P30872, P30873, P30937, P30992, P30993, P31391, P33766, P34976, P35373

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
PRKCB	down-regulates	C5AR1	phosphorylation
PRKCD	down-regulates	C5AR1	phosphorylation
C5	“up-regulates activity”	C5AR1	binding
C5AR1	up-regulates	Chemotaxis
Avacopan	“down-regulates activity”	C5AR1	binding
C5AR1	up-regulates	Inflammation
C5AR1	“up-regulates quantity by expression”	ITGAM
C5AR1	“up-regulates quantity by expression”	CR1
C5AR1	“down-regulates quantity by repression”	SELL
C5AR1	“up-regulates quantity by expression”	superoxide

Disease & clinical

Clinical variants and AI predictions

ClinVar

70 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	7
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

320 predictions. Top by Δscore:

Variant	Effect	Δscore
19:47319775:CCTTA:C	acceptor_loss	1.0000
19:47319776:CTTA:C	acceptor_loss	1.0000
19:47319777:TTAGG:T	acceptor_loss	1.0000
19:47319778:TAG:T	acceptor_loss	1.0000
19:47319779:A:C	acceptor_loss	1.0000
19:47319779:AG:A	acceptor_gain	1.0000
19:47319780:GG:G	acceptor_gain	1.0000
19:47319768:C:CA	acceptor_gain	0.9900
19:47319779:A:AG	acceptor_gain	0.9900
19:47319780:G:GG	acceptor_gain	0.9900
19:47319780:GGA:G	acceptor_gain	0.9900
19:47319780:GGACT:G	acceptor_gain	0.9900
19:47309895:CATGG:C	donor_loss	0.9800
19:47309897:TGG:T	donor_loss	0.9800
19:47309898:GGTG:G	donor_loss	0.9800
19:47309899:GT:G	donor_loss	0.9800
19:47309900:T:A	donor_loss	0.9800
19:47319780:GGAC:G	acceptor_gain	0.9800
19:47309899:G:GG	donor_gain	0.9700
19:47309895:CATG:C	donor_gain	0.9600
19:47309896:ATG:A	donor_gain	0.9500
19:47309897:TG:T	donor_gain	0.9500
19:47309898:GG:G	donor_gain	0.9500
19:47309894:ACATG:A	donor_gain	0.9200
19:47309901:GA:G	donor_loss	0.9000
19:47310463:TC:T	donor_gain	0.9000
19:47315453:G:GT	donor_gain	0.7500
19:47319771:T:G	acceptor_gain	0.7200
19:47319770:A:AG	acceptor_gain	0.7100
19:47315407:GAC:G	donor_gain	0.7000

AlphaMissense

2245 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:47320083:G:C	W102C	0.997
19:47320083:G:T	W102C	0.997
19:47320168:A:C	S131R	0.997
19:47320170:C:A	S131R	0.997
19:47320170:C:G	S131R	0.997
19:47320525:A:C	S250R	0.996
19:47320527:T:A	S250R	0.996
19:47320527:T:G	S250R	0.996
19:47319942:T:A	N55K	0.995
19:47319942:T:G	N55K	0.995
19:47320528:T:C	F251L	0.995
19:47320530:C:A	F251L	0.995
19:47320530:C:G	F251L	0.995
19:47320144:A:C	S123R	0.994
19:47320146:C:A	S123R	0.994
19:47320146:C:G	S123R	0.994
19:47320258:T:A	W161R	0.994
19:47320258:T:C	W161R	0.994
19:47319928:G:A	G51R	0.993
19:47319928:G:C	G51R	0.993
19:47320010:T:C	L78S	0.993
19:47320408:T:C	F211L	0.993
19:47320410:C:A	F211L	0.993
19:47320410:C:G	F211L	0.993
19:47320643:C:A	A289D	0.993
19:47320667:C:A	P297H	0.993
19:47320023:C:A	D82E	0.992
19:47320023:C:G	D82E	0.992
19:47320339:T:A	C188S	0.992
19:47320340:G:C	C188S	0.992

dbSNP variants (sampled 300 via entrez): RS1000264532 (19:47322349 G>A), RS1000373297 (19:47316441 C>A), RS1000846867 (19:47318411 A>G), RS1001015960 (19:47306006 G>A,C), RS1001149909 (19:47306350 A>G), RS1001263261 (19:47311657 C>A,G,T), RS1001481621 (19:47322296 C>T), RS1001621422 (19:47311214 G>A), RS1001742188 (19:47305689 A>G), RS1001861621 (19:47318457 C>T), RS1001934210 (19:47317027 GA>G,GAA), RS1002202665 (19:47321502 T>C), RS1002260230 (19:47317730 C>T), RS1002278858 (19:47307175 A>G), RS1002291399 (19:47317351 A>T)

Disease associations

OMIM: gene MIM:113995 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002524_1	Chronic periodontitis	3.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2373 (SINGLE PROTEIN), CHEMBL4523605 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 59,532 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1707	LOPERAMIDE HYDROCHLORIDE	4	59,532

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Complement peptide receptors

Most potent curated ligand interactions (24 total), top 24:

Ligand	Action	Affinity	Parameter
avacopan	Antagonist	9.7	pIC50
CHIPS	Antagonist	9.0	pKd
C5a	Full agonist	9.0	pEC50
[125I]C5a (human)	Full agonist	8.7	pKd
W54011	Antagonist	8.7	pKi
DF2593A	Antagonist	8.3	pIC50
BM221	Agonist	8.24	pEC50
ACT-1014-6470	Antagonist	7.96	pIC50
NDT9513727	Inverse agonist	7.94	pIC50
AcPhe-Orn-Pro-D-Cha-Trp-Arg	Antagonist	7.9	pIC50
PMX53	Antagonist	7.7	pIC50
N-methyl-Phe-Lys-Pro-D-Cha-Cha-D-Arg-CO2H	Full agonist	7.6	pIC50
A8Δ71-73	Antagonist	7.57	pIC50
PMX205	Antagonist	7.51	pIC50
NDT9520492	Antagonist	7.5	pKi
DF3016A	Antagonist	7.3	pIC50
BM213	Biased agonist	7.23	pEC50
N-methyl-Phe-Lys-Pro-D-Cha-Trp-D-Arg-CO2H	Antagonist	7.2	pIC50
JPE1375	Antagonist	7.0	pIC50
C089	Antagonist	6.7	pIC50
C5a des-Arg	Partial agonist	6.4	pIC50
RPR121154	Antagonist	6.1	pIC50
L-156,602	Antagonist	5.7	pIC50
YSFKPMPLaR	Agonist	5.5	pEC50

Binding affinities (BindingDB)

146 measured of 148 human assays (148 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-(2,6-dimethylphenyl)-4-[(2R,4R)-4-methoxy-2-methylpiperidin-1-yl]-6-(2-methyl-5-propan-2-ylphenyl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	0.5 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
6-(3-cyclopropyl-1-methylpyrazol-5-yl)-2-(3,5-dimethyl-2H-indazol-4-yl)-4-[(4R)-4-methoxy-3,3-dimethylpiperidin-1-yl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	0.5 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
2-(3,5-dimethyl-2H-indazol-4-yl)-4-[(3R,4R)-4-methoxy-3-methylpiperidin-1-yl]-6-(2-methyl-5-propan-2-ylphenyl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	1 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
2-(3,5-dimethyl-2H-indazol-4-yl)-4-[(2R,4R)-4-methoxy-2-methylpiperidin-1-yl]-6-(2-methyl-5-propan-2-ylphenyl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	1 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
2-(3,5-dimethyl-2H-indazol-4-yl)-4-[(2R,4R)-4-methoxy-2-methylpiperidin-1-yl]-6-[2-methyl-5-(3-methyloxetan-3-yl)phenyl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	1 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
6-(5-chloro-2-methylphenyl)-2-(3,5-dimethyl-2H-indazol-4-yl)-4-[(2R,4R)-4-methoxy-2-methylpiperidin-1-yl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	1 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
2-(3,5-dimethyl-2H-indazol-4-yl)-4-[(2R,4R)-4-methoxy-2-methylpiperidin-1-yl]-6-[2-methyl-5-(trifluoromethyl)phenyl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	1 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
2-(3,5-dimethyl-2H-indazol-4-yl)-4-[(4R)-4-methoxy-3,3-dimethylpiperidin-1-yl]-6-(2-methyl-5-propan-2-ylphenyl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	1 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
2-(3,5-dimethyl-2H-indazol-4-yl)-4-[(2R,4R)-4-ethoxy-2-methylpiperidin-1-yl]-6-(2-methyl-5-propan-2-ylphenyl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	1 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
2-(3,5-dimethyl-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-4-yl)-4-[(2R)-2-methylpiperidin-1-yl]-6-(2-methyl-5-propan-2-ylphenyl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	1 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
6-(3-cyclopropyl-1-methylpyrazol-5-yl)-2-(3,5-dimethyl-2H-indazol-4-yl)-4-[(2R,4R)-4-methoxy-2-methylpiperidin-1-yl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	1 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
2-[(3R)-3-methyl-4-[2-(3-methyl-1H-indol-4-yl)-6-(2-methyl-5-propan-2-ylphenyl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-4-yl]piperazin-1-yl]acetamide	IC50	1 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
6-[4-chloro-3-(difluoromethyl)-1-methylpyrazol-5-yl]-2-(3,5-dimethyl-2H-indazol-4-yl)-4-[(4R)-4-methoxy-3,3-dimethylpiperidin-1-yl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	1 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
6-(4-chloro-3-cyclopropyl-1-methylpyrazol-5-yl)-2-(3,5-dimethyl-2H-indazol-4-yl)-4-[(2R,4R)-4-methoxy-2-methylpiperidin-1-yl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	1 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
6-(3-cyclopropyl-4-fluoro-1-methylpyrazol-5-yl)-2-(3,5-dimethyl-2H-indazol-4-yl)-4-[(4S)-4-methoxy-3,3-dimethylpiperidin-1-yl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	1 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
6-[3-(difluoromethyl)-4-fluoro-1-methylpyrazol-5-yl]-2-(3,5-dimethyl-2H-indazol-4-yl)-4-[(4R)-4-methoxy-3,3-dimethylpiperidin-1-yl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	1 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
1-[2-(3,5-dimethyl-2H-indazol-4-yl)-6-(2-methyl-5-propan-2-ylphenyl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-4-yl]-N,N-dimethylazetidin-3-amine	IC50	1 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
2-(3,5-dimethyl-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-4-yl)-4-(2-methylazetidin-1-yl)-6-(2-methyl-5-propan-2-ylphenyl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	1 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
(1S,6S)-3-[6-(4-chloro-3-cyclopropyl-1-methylpyrazol-5-yl)-2-(3,5-dimethyl-2H-indazol-4-yl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-4-yl]-1-methyl-7-oxa-3-azabicyclo[4.2.0]octane	IC50	1 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
4-[(4R)-4-methoxy-3,3-dimethylpiperidin-1-yl]-2-(3-methyl-1H-indol-4-yl)-6-(2-methyl-5-propan-2-ylphenyl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	2 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
2-(2,6-dimethylphenyl)-4-[(4S)-4-methoxy-3,3-dimethylpiperidin-1-yl]-6-(2-methyl-5-propan-2-ylphenyl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	2 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
2-(3,5-dimethyl-2H-indazol-4-yl)-4-[(4S)-4-methoxy-3,3-dimethylpiperidin-1-yl]-6-(2-methyl-5-propan-2-ylphenyl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	2 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
2-(2,6-dimethylphenyl)-4-[(2R,4R)-4-methoxy-2-methylpiperidin-1-yl]-6-[2-methyl-5-(3-methyloxetan-3-yl)phenyl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	2 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
2-(2,6-dimethylphenyl)-6-(5-methoxy-2-methylphenyl)-4-[(2R,4R)-4-methoxy-2-methylpiperidin-1-yl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	2 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
4-[(2R,4R)-4-methoxy-2-methylpiperidin-1-yl]-6-(2-methyl-5-propan-2-ylphenyl)-2-[5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	2 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
2-(3,5-dimethyl-2H-indazol-4-yl)-4-[(2R,4R)-4-methoxy-2-methylpiperidin-1-yl]-6-(1-methyl-3-propan-2-ylpyrazol-5-yl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	2 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
2-(3-methyl-1H-indol-4-yl)-4-[(3R)-3-methyl-4-methylsulfonylpiperazin-1-yl]-6-(2-methyl-5-propan-2-ylphenyl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	2 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
2-(3-chloro-5-methyl-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-4-yl)-4-[(4S)-4-methoxy-3,3-dimethylpiperidin-1-yl]-6-(2-methyl-5-propan-2-ylphenyl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	2 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
6-(4-chloro-1-methyl-3-propan-2-ylpyrazol-5-yl)-2-(3,5-dimethyl-2H-indazol-4-yl)-4-[(2R,4R)-4-methoxy-2-methylpiperidin-1-yl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	2 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
6-(4-chloro-3-cyclopropyl-1-methylpyrazol-5-yl)-2-(3,5-dimethyl-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-4-yl)-4-[(4R)-4-methoxy-3,3-dimethylpiperidin-1-yl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	2 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
6-(3-cyclopropyl-4-fluoro-1-methylpyrazol-5-yl)-2-(3,5-dimethyl-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-4-yl)-4-[(1S,5R)-3-methoxy-8-azabicyclo[3.2.1]octan-8-yl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	2 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
6-(3-cyclopropyl-4-fluoro-1-methylpyrazol-5-yl)-2-(3,5-dimethyl-2H-indazol-4-yl)-4-[(4R)-4-ethoxy-3,3-dimethylpiperidin-1-yl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	2 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
(3R)-1-[2-(3,5-dimethyl-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-4-yl)-6-(2-methyl-5-propan-2-ylphenyl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-4-yl]-N,N-dimethylpyrrolidin-3-amine	IC50	2 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
(3R)-4-[2-(3,5-dimethyl-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-4-yl)-6-(2-methyl-5-propan-2-ylphenyl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-4-yl]-3-methylmorpholine	IC50	2 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
6-(4-chloro-3-cyclopropyl-1-methylpyrazol-5-yl)-2-(3,5-dimethyl-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-4-yl)-4-(3-ethoxyazetidin-1-yl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	2 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
6-(3-cyclopropyl-1-ethyl-4-fluoropyrazol-5-yl)-2-(3,5-dimethyl-2H-indazol-4-yl)-4-[(4R)-4-methoxy-3,3-dimethylpiperidin-1-yl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	2 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
2-[(2S,5R)-4-[2-(2,6-dimethylphenyl)-6-(2-methyl-5-propan-2-ylphenyl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-4-yl]-2,5-dimethylpiperazin-1-yl]acetamide	IC50	3 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
4-methyl-6-(2-methyl-5-propan-2-ylphenyl)-2-(5-propan-2-yl-1H-indazol-4-yl)-7,8-dihydro-5H-1,6-naphthyridine	IC50	3 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
6-(4-chloro-3-cyclopropyl-1-methylpyrazol-5-yl)-2-(3,5-dimethyl-2H-indazol-4-yl)-4-[(4S)-4-methoxy-3,3-dimethylpiperidin-1-yl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	3 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
6-benzyl-2-chloro-4-methoxy-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	4 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
2-(3,5-dimethyl-2H-indazol-4-yl)-4-[(1S,5R)-3-methoxy-8-azabicyclo[3.2.1]octan-8-yl]-6-(2-methyl-5-propan-2-ylphenyl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	4 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
4-[(4S)-4-methoxy-3,3-dimethylpiperidin-1-yl]-6-[2-methyl-5-(3-methyloxetan-3-yl)phenyl]-2-(5-propan-2-yl-1H-indazol-4-yl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	4 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
4-[(4S)-4-methoxy-3,3-dimethylpiperidin-1-yl]-6-(5-methoxy-2-methylphenyl)-2-(5-propan-2-yl-1H-indazol-4-yl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	4 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
2-(2-chloro-6-methylphenyl)-4-[(3R,4R)-4-methoxy-3-methylpiperidin-1-yl]-6-(2-methyl-5-propan-2-ylphenyl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	4 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
2-(2,6-dimethylphenyl)-4-[(4R)-4-methoxy-3,3-dimethylpiperidin-1-yl]-6-[2-methyl-5-(trifluoromethyl)phenyl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	4 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
2-(7-fluoro-3-methyl-1H-indol-4-yl)-4-[(4S)-4-methoxy-3,3-dimethylpiperidin-1-yl]-6-(2-methyl-5-propan-2-ylphenyl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	4 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
2-[(2S,5R)-2,5-dimethyl-4-[2-(3-methyl-1H-indol-4-yl)-6-(2-methyl-5-propan-2-ylphenyl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-4-yl]piperazin-1-yl]acetamide	IC50	4 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
6-(4-chloro-3-cyclopropyl-1-methylpyrazol-5-yl)-2-(3,5-dimethyl-2H-indazol-4-yl)-4-[(4R)-4-ethoxy-3,3-dimethylpiperidin-1-yl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine	IC50	4 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
(3S)-1-[2-(3,5-dimethyl-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-4-yl)-6-(2-methyl-5-propan-2-ylphenyl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-4-yl]-4-methoxy-N,N-dimethylpyrrolidin-3-amine	IC50	4 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
(2S,3R)-1-[6-(4-chloro-3-cyclopropyl-1-methylpyrazol-5-yl)-2-(3,5-dimethyl-2H-indazol-4-yl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-4-yl]-2-methylazetidin-3-ol	IC50	4 nM	US-8846656: Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators

ChEMBL bioactivities

933 potent at pChembl≥5 of 987 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.30	IC50	0.5	nM	CHEMBL3646964
9.30	IC50	0.5	nM	CHEMBL3646938
9.00	IC50	1	nM	CHEMBL3646945
9.00	IC50	1	nM	CHEMBL3646963
9.00	IC50	1	nM	CHEMBL3646952
9.00	IC50	1	nM	CHEMBL3646951
9.00	IC50	1	nM	CHEMBL3646934
9.00	IC50	1	nM	CHEMBL3646944
9.00	IC50	1	nM	CHEMBL3647006
9.00	IC50	1	nM	CHEMBL3646953
9.00	IC50	1	nM	CHEMBL3647001
9.00	IC50	1	nM	CHEMBL3647009
9.00	IC50	1	nM	CHEMBL3647012
9.00	IC50	1	nM	CHEMBL3647014
9.00	IC50	1	nM	CHEMBL3646957
9.00	IC50	1	nM	CHEMBL3646956
9.00	IC50	1	nM	CHEMBL3647018
9.00	IC50	1	nM	CHEMBL3647028
9.00	IC50	1	nM	CHEMBL3647021
9.00	IC50	1	nM	CHEMBL4245250
8.89	EC50	1.3	nM	ISHKDMQLGR
8.82	IC50	1.5	nM	CHEMBL486749
8.81	EC50	1.538	nM	CHEMBL5082686
8.70	IC50	2	nM	CHEMBL3646979
8.70	IC50	2	nM	CHEMBL3646958
8.70	IC50	2	nM	CHEMBL3647003
8.70	IC50	2	nM	CHEMBL3646913
8.70	IC50	2	nM	CHEMBL3646962
8.70	IC50	2	nM	CHEMBL3646932
8.70	IC50	2	nM	CHEMBL3646936
8.70	IC50	2	nM	CHEMBL3646984
8.70	IC50	2	nM	CHEMBL3647004
8.70	IC50	2	nM	CHEMBL3647011
8.70	IC50	2	nM	CHEMBL3646942
8.70	IC50	2	nM	CHEMBL3646940
8.70	IC50	2	nM	CHEMBL3647013
8.70	IC50	2	nM	CHEMBL3647023
8.70	IC50	2	nM	CHEMBL3647019
8.70	IC50	2	nM	CHEMBL3647022
8.70	IC50	2	nM	CHEMBL3647033
8.70	IC50	2	nM	CHEMBL1628668
8.59	EC50	2.588	nM	CHEMBL5092578
8.52	IC50	3	nM	CHEMBL3647008
8.52	IC50	3	nM	CHEMBL3646977
8.52	IC50	3	nM	CHEMBL3646994
8.52	IC50	3	nM	CHEMBL1628668
8.52	IC50	3	nM	CHEMBL465377
8.40	IC50	4	nM	CHEMBL3646924
8.40	IC50	4	nM	CHEMBL3646950
8.40	IC50	4	nM	CHEMBL3646933

PubChem BioAssay actives

370 with measured affinity, of 835 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N,N-bis(1,3-benzodioxol-5-ylmethyl)-3-butyl-2,5-diphenylimidazol-4-amine	1393272: Antagonist activity at recombinant human C5aR1 expressed in Sf9 insect cell membranes co-expressing G-alphai2,G-beta1 and G-gamma2 assessed as inhibition of recombinant human C5a-induced [35S]GTPgammaS binding after 60 mins by liquid scintillation spectrometry	ic50	0.0010	uM
(2S)-2-[[2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-amino-3-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]hexanoyl]amino]-3-carboxypropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-5-(diaminomethylideneamino)pentanoic acid	160510: Ability to induce shape change (polarization) in human polymorphonuclear leukocytes (PMN)	ec50	0.0013	uM
(2S)-2-[[(2S)-2-[[(2R,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-acetamido-3-phenylpropanoyl]amino]-6-aminohexanoyl]pyrrolidine-2-carbonyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	1833593: Agonist activity at human C5aR1 expressed in CHO cells assessed as induction of ERK1/2 phosphorylation at Thr202/Tyr204 residues incubated for 10 mins by AlphaLISA assay	ec50	0.0015	uM
N-[2-(4-chlorophenyl)ethyl]-N-(1,4-dioxaspiro[4.5]decan-8-yl)-2-(2-methylpropyl)benzamide	348779: Displacement of [125I]r-hC5a from C5a receptor in cAMP differentiated human U937 cells	ic50	0.0015	uM
N-[[4-(dimethylamino)phenyl]methyl]-7-methoxy-N-(4-propan-2-ylphenyl)-1,2,3,4-tetrahydronaphthalene-1-carboxamide	1393271: Antagonist activity at C5aR1 in human neutrophils assessed as inhibition of 0.1 nM recombinant human C5a-induced intracellular calcium release	ic50	0.0020	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-acetamido-3-phenylpropanoyl]amino]-6-aminohexanoyl]pyrrolidine-2-carbonyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]pentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	1833593: Agonist activity at human C5aR1 expressed in CHO cells assessed as induction of ERK1/2 phosphorylation at Thr202/Tyr204 residues incubated for 10 mins by AlphaLISA assay	ec50	0.0026	uM
ethyl 3-(4-chlorophenyl)-2-[1,4-dioxaspiro[4.5]decan-8-yl(naphthalene-1-carbonyl)amino]propanoate	395877: Displacement of [125I]C5a from C5a receptor in cAMP differentiated human U937 cells by filtration assay	ic50	0.0030	uM
(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	1833593: Agonist activity at human C5aR1 expressed in CHO cells assessed as induction of ERK1/2 phosphorylation at Thr202/Tyr204 residues incubated for 10 mins by AlphaLISA assay	ec50	0.0043	uM
N-[2-(4-chlorophenyl)ethyl]-N-(1-oxaspiro[4.5]decan-8-yl)-1-benzothiophene-3-carboxamide	348779: Displacement of [125I]r-hC5a from C5a receptor in cAMP differentiated human U937 cells	ic50	0.0050	uM
ethyl 2-[1-benzothiophene-3-carbonyl(1,4-dioxaspiro[4.5]decan-8-yl)amino]-3-(4-chlorophenyl)propanoate	348779: Displacement of [125I]r-hC5a from C5a receptor in cAMP differentiated human U937 cells	ic50	0.0050	uM
(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-acetamido-3-phenylpropanoyl]amino]-6-aminohexanoyl]pyrrolidine-2-carbonyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]butanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	1833593: Agonist activity at human C5aR1 expressed in CHO cells assessed as induction of ERK1/2 phosphorylation at Thr202/Tyr204 residues incubated for 10 mins by AlphaLISA assay	ec50	0.0058	uM
(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-acetamido-3-phenylpropanoyl]amino]-6-aminohexanoyl]pyrrolidine-2-carbonyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	1833593: Agonist activity at human C5aR1 expressed in CHO cells assessed as induction of ERK1/2 phosphorylation at Thr202/Tyr204 residues incubated for 10 mins by AlphaLISA assay	ec50	0.0066	uM
N,4-dimethyl-N-[2-[methyl-(4-methylphenyl)sulfonylamino]phenyl]benzenesulfonamide	453693: Antagonist activity at C5a receptor in human PMNC assessed as inhibition of anaphylatoxin C5a-induced intracellular calcium accumulation after 10 mins by FLIPR assay	ic50	0.0067	uM
2-[2-[[2-(2,6-diethylphenyl)-4-propan-2-yloxy-5,6,7,8-tetrahydroquinolin-5-yl]amino]phenyl]ethanol	340482: Antagonist activity at human recombinant C5a receptor in U937 cells assessed as inhibition of C5a-induced calcium mobilization by FLIPR assay	ic50	0.0070	uM
2-(2,6-diethylphenyl)-4-methoxy-N-methyl-N-naphthalen-1-yl-5,6,7,8-tetrahydroquinolin-5-amine	329891: Displacement of [125I]C5a from human C5a receptor in U937 cells	ki	0.0073	uM
N-[2-(4-chlorophenyl)-1-(5-methyl-1,2,4-oxadiazol-3-yl)ethyl]-N-(1,4-dioxaspiro[4.5]decan-8-yl)-2-ethylbenzamide	395877: Displacement of [125I]C5a from C5a receptor in cAMP differentiated human U937 cells by filtration assay	ic50	0.0080	uM
2-(2,6-diethylphenyl)-N-ethyl-4-methoxy-N-naphthalen-1-yl-5,6,7,8-tetrahydroquinolin-5-amine	329891: Displacement of [125I]C5a from human C5a receptor in U937 cells	ki	0.0089	uM
2-(2,6-diethylphenyl)-4-methoxy-5-[8-(trifluoromethyl)-3,4-dihydro-1H-isoquinolin-2-yl]-5,6,7,8-tetrahydroquinoline	329891: Displacement of [125I]C5a from human C5a receptor in U937 cells	ki	0.0097	uM
2-(2,6-diethylphenyl)-4-methoxy-N-(5-methoxy-2-methylphenyl)-5,6,7,8-tetrahydroquinolin-5-amine	340483: Displacement of [125I]C5a from human recombinant C5a receptor in U937 cells	ki	0.0100	uM
(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	1833593: Agonist activity at human C5aR1 expressed in CHO cells assessed as induction of ERK1/2 phosphorylation at Thr202/Tyr204 residues incubated for 10 mins by AlphaLISA assay	ec50	0.0104	uM
(2S)-2-acetamido-N-[(3S,9R,12S,15R,18S)-15-(cyclohexylmethyl)-9-[3-(diaminomethylideneamino)propyl]-12-(1H-indol-3-ylmethyl)-2,8,11,14,17-pentaoxo-1,7,10,13,16-pentazabicyclo[16.3.0]henicosan-3-yl]-3-phenylpropanamide	160163: 50% reduction in myeloperoxidase secretion from human PMNs mediated by 100 nM C5a	ic50	0.0120	uM
4-methoxy-1-[1-(2-methoxy-6-methylphenyl)piperidin-4-yl]-3-[[2-(trifluoromethyl)phenyl]methyl]benzimidazol-2-one	2091019: Antagonist activity at recombinant human ProLink-tagged C5aR1 expressed in CHO-K1 cells assessed as reduction in hC5a stimulated beta-arrestin-2 recruitment by DISCO assay	ic50	0.0120	uM
N-[1-(4-chlorophenyl)-3-methoxypropan-2-yl]-N-(1,4-dioxaspiro[4.5]decan-8-yl)-1-benzothiophene-3-carboxamide	395877: Displacement of [125I]C5a from C5a receptor in cAMP differentiated human U937 cells by filtration assay	ic50	0.0120	uM
[5-chloro-2-[[2-(2,6-diethylphenyl)-4-methoxy-5,6,7,8-tetrahydroquinolin-5-yl]amino]phenyl]methanol	340483: Displacement of [125I]C5a from human recombinant C5a receptor in U937 cells	ki	0.0130	uM
N-[1-(4-chlorophenyl)-3-(dimethylamino)propan-2-yl]-N-(1,4-dioxaspiro[4.5]decan-8-yl)naphthalene-1-carboxamide	395877: Displacement of [125I]C5a from C5a receptor in cAMP differentiated human U937 cells by filtration assay	ic50	0.0130	uM
3-[1-(2-fluoro-6-methylphenyl)piperidin-4-yl]-1-[[2-(trifluoromethyl)phenyl]methyl]-4H-quinazolin-2-one	2091070: Binding affinity to C5aR in human whole blood assessed as dissociation constant by Schild plot analysis	kd	0.0150	uM
methyl 2-[1-benzothiophene-3-carbonyl(1,4-dioxaspiro[4.5]decan-8-yl)amino]-3-(4-chlorophenyl)propanoate	395877: Displacement of [125I]C5a from C5a receptor in cAMP differentiated human U937 cells by filtration assay	ic50	0.0150	uM
(2S)-2-acetamido-N-[(3S,9S,12S,15R,18S)-15-(cyclohexylmethyl)-9-[3-(diaminomethylideneamino)propyl]-12-(1H-indol-3-ylmethyl)-2,8,11,14,17-pentaoxo-1,7,10,13,16-pentazabicyclo[16.3.0]henicosan-3-yl]-3-phenylpropanamide	491628: Displacement of [125I-C5a] from C5a receptor in human PBMC by scintillation counting	ic50	0.0150	uM
(2S)-N-(2,3-dihydro-1H-inden-2-yl)-N-[(2-fluorophenyl)methyl]-2-[(1R)-1-naphthalen-1-yl-3,4-dihydro-1H-isoquinolin-2-yl]propanamide	1393272: Antagonist activity at recombinant human C5aR1 expressed in Sf9 insect cell membranes co-expressing G-alphai2,G-beta1 and G-gamma2 assessed as inhibition of recombinant human C5a-induced [35S]GTPgammaS binding after 60 mins by liquid scintillation spectrometry	ki	0.0152	uM
1-[(3R)-1-(2,6-dimethylphenyl)pyrrolidin-3-yl]-4-methoxy-3-[[2-(trifluoromethyl)phenyl]methyl]benzimidazol-2-one	2091019: Antagonist activity at recombinant human ProLink-tagged C5aR1 expressed in CHO-K1 cells assessed as reduction in hC5a stimulated beta-arrestin-2 recruitment by DISCO assay	ic50	0.0160	uM
1-[1-(2-fluoro-6-methylphenyl)piperidin-4-yl]-4-methoxy-3-[[2-(trifluoromethyl)phenyl]methyl]benzimidazol-2-one	2091019: Antagonist activity at recombinant human ProLink-tagged C5aR1 expressed in CHO-K1 cells assessed as reduction in hC5a stimulated beta-arrestin-2 recruitment by DISCO assay	ic50	0.0160	uM
1-[(3R)-1-(2-fluoro-6-methoxyphenyl)pyrrolidin-3-yl]-4-methoxy-3-[[2-(trifluoromethyl)phenyl]methyl]benzimidazol-2-one	2091019: Antagonist activity at recombinant human ProLink-tagged C5aR1 expressed in CHO-K1 cells assessed as reduction in hC5a stimulated beta-arrestin-2 recruitment by DISCO assay	ic50	0.0160	uM
1-[(3R)-1-(2-fluoro-6-methylphenyl)pyrrolidin-3-yl]-4-methoxy-3-[[2-(trifluoromethyl)phenyl]methyl]benzimidazol-2-one	2091019: Antagonist activity at recombinant human ProLink-tagged C5aR1 expressed in CHO-K1 cells assessed as reduction in hC5a stimulated beta-arrestin-2 recruitment by DISCO assay	ic50	0.0170	uM
(2S)-2-acetamido-N-[(3S,9S,12S,15R,18S)-15-(cyclohexylmethyl)-12-(1H-indol-3-ylmethyl)-2,8,11,14,17-pentaoxo-9-propyl-1,7,10,13,16-pentazabicyclo[16.3.0]henicosan-3-yl]-3-phenylpropanamide	270448: Antagonist activity at human C5aR in CD88 transfected RBL cells assessed as inhibition of C5a-induced glucosaminidase release	ic50	0.0180	uM
(2S)-2-acetamido-N-[(3S,9S,12S,15R,18S)-9-(3-aminopropyl)-15-(cyclohexylmethyl)-12-(1H-indol-3-ylmethyl)-2,8,11,14,17-pentaoxo-1,7,10,13,16-pentazabicyclo[16.3.0]henicosan-3-yl]-3-phenylpropanamide	270448: Antagonist activity at human C5aR in CD88 transfected RBL cells assessed as inhibition of C5a-induced glucosaminidase release	ic50	0.0180	uM
N-[2-(4-chlorophenyl)ethyl]-N-(1,4-dioxaspiro[4.5]decan-8-yl)-2-ethylbenzamide	348779: Displacement of [125I]r-hC5a from C5a receptor in cAMP differentiated human U937 cells	ic50	0.0180	uM
1-[(3R)-1-(2,6-difluorophenyl)pyrrolidin-3-yl]-4-methoxy-3-[[2-(trifluoromethyl)phenyl]methyl]benzimidazol-2-one	2091019: Antagonist activity at recombinant human ProLink-tagged C5aR1 expressed in CHO-K1 cells assessed as reduction in hC5a stimulated beta-arrestin-2 recruitment by DISCO assay	ic50	0.0190	uM
4-methoxy-1-[(3R)-1-(2-methoxy-6-methylphenyl)pyrrolidin-3-yl]-3-[[2-(trifluoromethyl)phenyl]methyl]benzimidazol-2-one	2091019: Antagonist activity at recombinant human ProLink-tagged C5aR1 expressed in CHO-K1 cells assessed as reduction in hC5a stimulated beta-arrestin-2 recruitment by DISCO assay	ic50	0.0190	uM
(2S)-2-acetamido-N-[(3S,9S,12S,15R,18S)-9-(cyanomethyl)-15-(cyclohexylmethyl)-12-(1H-indol-3-ylmethyl)-2,8,11,14,17-pentaoxo-1,7,10,13,16-pentazabicyclo[16.3.0]henicosan-3-yl]-3-phenylpropanamide	270448: Antagonist activity at human C5aR in CD88 transfected RBL cells assessed as inhibition of C5a-induced glucosaminidase release	ic50	0.0190	uM
(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]hexanoyl]amino]propanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	1833593: Agonist activity at human C5aR1 expressed in CHO cells assessed as induction of ERK1/2 phosphorylation at Thr202/Tyr204 residues incubated for 10 mins by AlphaLISA assay	ec50	0.0195	uM
N-(2,4-dimethoxyphenyl)-N-[1-(2-fluorophenyl)-2-[[(2R)-2-hydroxypropyl]amino]-2-oxoethyl]-3-methylfuran-2-carboxamide	393034: Antagonist activity at human recombinant C5a receptor in HEK cells assessed as inhibition of C5a-induced calcium mobilization	ic50	0.0199	uM
1-[1-(2,6-dimethylphenyl)piperidin-4-yl]-4-methoxy-3-[[2-(trifluoromethyl)phenyl]methyl]benzimidazol-2-one	2091019: Antagonist activity at recombinant human ProLink-tagged C5aR1 expressed in CHO-K1 cells assessed as reduction in hC5a stimulated beta-arrestin-2 recruitment by DISCO assay	ic50	0.0210	uM
2-[2-[[2-(2,6-diethylphenyl)-4-methoxy-5,6,7,8-tetrahydroquinolin-5-yl]amino]phenyl]ethanol	340483: Displacement of [125I]C5a from human recombinant C5a receptor in U937 cells	ki	0.0210	uM
1-[1-(2,6-dimethoxyphenyl)piperidin-4-yl]-4-methoxy-3-[[2-(trifluoromethyl)phenyl]methyl]benzimidazol-2-one	2091019: Antagonist activity at recombinant human ProLink-tagged C5aR1 expressed in CHO-K1 cells assessed as reduction in hC5a stimulated beta-arrestin-2 recruitment by DISCO assay	ic50	0.0220	uM
1-[(3R)-1-(2,6-dimethoxyphenyl)pyrrolidin-3-yl]-4-methoxy-3-[[2-(trifluoromethyl)phenyl]methyl]benzimidazol-2-one	2091019: Antagonist activity at recombinant human ProLink-tagged C5aR1 expressed in CHO-K1 cells assessed as reduction in hC5a stimulated beta-arrestin-2 recruitment by DISCO assay	ic50	0.0220	uM
(2S)-2-acetamido-N-[(3S,9S,12S,15R,18S)-15-(cyclohexylmethyl)-12-(1H-indol-3-ylmethyl)-2,8,11,14,17-pentaoxo-9-(thiophen-2-ylmethyl)-1,7,10,13,16-pentazabicyclo[16.3.0]henicosan-3-yl]-3-phenylpropanamide	270448: Antagonist activity at human C5aR in CD88 transfected RBL cells assessed as inhibition of C5a-induced glucosaminidase release	ic50	0.0220	uM
[2-[[2-(2,6-diethylphenyl)-4-methoxy-5,6,7,8-tetrahydroquinolin-5-yl]amino]-4-(trifluoromethyl)phenyl]methanol	340482: Antagonist activity at human recombinant C5a receptor in U937 cells assessed as inhibition of C5a-induced calcium mobilization by FLIPR assay	ic50	0.0220	uM
3-[1-(2,6-dimethylphenyl)piperidin-4-yl]-1-[[2-(trifluoromethyl)phenyl]methyl]-4H-quinazolin-2-one	2091019: Antagonist activity at recombinant human ProLink-tagged C5aR1 expressed in CHO-K1 cells assessed as reduction in hC5a stimulated beta-arrestin-2 recruitment by DISCO assay	ic50	0.0230	uM
(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	1833593: Agonist activity at human C5aR1 expressed in CHO cells assessed as induction of ERK1/2 phosphorylation at Thr202/Tyr204 residues incubated for 10 mins by AlphaLISA assay	ec50	0.0244	uM
3-[(3R)-1-(2,6-dimethylphenyl)pyrrolidin-3-yl]-1-[[2-(trifluoromethyl)phenyl]methyl]-4H-quinazolin-2-one	2091019: Antagonist activity at recombinant human ProLink-tagged C5aR1 expressed in CHO-K1 cells assessed as reduction in hC5a stimulated beta-arrestin-2 recruitment by DISCO assay	ic50	0.0250	uM

CTD chemical–gene interactions

52 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases mutagenesis, affects methylation	4
Tetrachlorodibenzodioxin	increases expression	3
Cyclosporine	increases expression	3
sodium arsenite	decreases expression, increases expression	2
Nickel	increases expression	2
Silicon Dioxide	decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Asbestos, Crocidolite	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
Asian ginseng	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
lead acetate	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
dimethylselenide	increases expression, increases oxidation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
3,4,3’,4’-tetrachlorobiphenyl	affects expression	1
aflatoxin B2	increases methylation	1
tris(chloroethyl)phosphate	increases expression	1
resorcinol	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
tri-(2-chloroisopropyl)phosphate	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	decreases expression	1
fenbuconazole	decreases expression	1
jinfukang	decreases expression	1
PCI 5002	increases expression, affects cotreatment	1

ChEMBL screening assays

139 unique, capped per target: 81 binding, 58 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1008821	Binding	Displacement of [125I]r-hC5a from C5a receptor in cAMP differentiated human U937 cells	Small, non-peptide C5a receptor antagonists: part 1. — Bioorg Med Chem Lett
CHEMBL1019505	Functional	Antagonist activity at C5a receptor assessed as inhibition of C5a-induced elastase release in human neutrophils during degranulation preincubated 5 mins prior to C5a challenge using p-nitroanilide as substrate	Small, non-peptide C5a receptor antagonists: part 2. — Bioorg Med Chem Lett

Cellosaurus cell lines

9 cell lines: 5 cancer cell line, 4 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8C9	Abcam HCT 116 C5AR1 KO	Cancer cell line	Male
CVCL_B9EF	Abcam A-549 C5AR1 KO	Cancer cell line	Male
CVCL_D2E2	Abcam MCF-7 C5AR1 KO	Cancer cell line	Female
CVCL_D8I0	Ubigene HCT 116 C5AR1 KO	Cancer cell line	Male
CVCL_H407	CHO-K1/C5a/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KU83	cAMP Hunter CHO-K1 C5AR1 Gi	Spontaneously immortalized cell line	Female
CVCL_KW45	PathHunter CHO-K1 C5AR1 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_KZ85	PathHunter U2OS C5AR1 Activated GPCR Internalization	Cancer cell line	Female
CVCL_ZJ77	GeneBLAzer C5aR1-Galpha15-NFAT-bla CHO-K1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.