CFD

Summary

CFD (complement factor D, HGNC:2771) is a protein-coding gene on chromosome 19p13.3, encoding Complement factor D (P00746). Serine protease that initiates the alternative pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system.

This gene encodes a member of the S1, or chymotrypsin, family of serine peptidases. This protease catalyzes the cleavage of factor B, the rate-limiting step of the alternative pathway of complement activation. This protein also functions as an adipokine, a cell signaling protein secreted by adipocytes, which regulates insulin secretion in mice. Mutations in this gene underlie complement factor D deficiency, which is associated with recurrent bacterial meningitis infections in human patients. Alternative splicing of this gene results in multiple transcript variants. At least one of these variants encodes a preproprotein that is proteolytically processed to generate the mature protease.

Source: NCBI Gene 1675 — RefSeq curated summary.

At a glance

• Gene–disease (curated): recurrent Neisseria infections due to factor D deficiency (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 321 total — 9 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 3
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001928

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2771
Approved symbol	CFD
Name	complement factor D
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	ADN
Ensembl gene	ENSG00000197766
Ensembl biotype	protein_coding
OMIM	134350
Entrez	1675

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000327726, ENST00000592860, ENST00000695942, ENST00000695943, ENST00000695944, ENST00000695945, ENST00000695946, ENST00000866187, ENST00000965842

RefSeq mRNA: 2 — MANE Select: NM_001928 NM_001317335, NM_001928

CCDS: CCDS12046, CCDS82261

Canonical transcript exons

ENST00000327726 — 5 exons

Exon	Start	End
ENSE00001231555	860861	861005
ENSE00001374327	861699	861956
ENSE00003965553	863092	863641
ENSE00003965554	860617	860773
ENSE00003965558	859664	859744

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 99.71.

FANTOM5 (CAGE): breadth broad, TPM avg 134.2784 / max 8799.6452, expressed in 870 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
172800	133.8404	868
172799	0.4380	168

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
subcutaneous adipose tissue	UBERON:0002190	99.71	gold quality
adipose tissue	UBERON:0001013	99.64	gold quality
mucosa of stomach	UBERON:0001199	99.63	gold quality
omental fat pad	UBERON:0010414	99.60	gold quality
right coronary artery	UBERON:0001625	99.52	gold quality
right atrium auricular region	UBERON:0006631	99.44	gold quality
apex of heart	UBERON:0002098	99.24	gold quality
vagina	UBERON:0000996	99.23	gold quality
tibial nerve	UBERON:0001323	99.23	gold quality
right lung	UBERON:0002167	99.23	gold quality
left coronary artery	UBERON:0001626	99.19	gold quality
fundus of stomach	UBERON:0001160	99.17	gold quality
endocervix	UBERON:0000458	99.12	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.04	gold quality
skin of abdomen	UBERON:0001416	98.99	gold quality
ectocervix	UBERON:0012249	98.94	gold quality
skin of leg	UBERON:0001511	98.91	gold quality
left uterine tube	UBERON:0001303	98.85	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.77	gold quality
lower esophagus	UBERON:0013473	98.75	gold quality
zone of skin	UBERON:0000014	98.64	gold quality
right lobe of thyroid gland	UBERON:0001119	98.59	gold quality
thoracic mammary gland	UBERON:0005200	98.55	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.15	gold quality
heart left ventricle	UBERON:0002084	98.02	gold quality
left lobe of thyroid gland	UBERON:0001120	97.92	gold quality
popliteal artery	UBERON:0002250	97.92	gold quality
tibial artery	UBERON:0007610	97.92	gold quality
transverse colon	UBERON:0001157	97.87	gold quality
upper lobe of left lung	UBERON:0008952	97.81	gold quality

Single-cell (SCXA)

Detected in 39 experiment(s), a significant marker in 37.

Experiment	Marker?	Max mean expression
E-HCAD-36	yes	15088.57
E-MTAB-8322	yes	13487.77
E-MTAB-8410	yes	12995.91
E-MTAB-8495	yes	10336.81
E-CURD-126	yes	8539.47
E-CURD-79	yes	8083.20
E-MTAB-9543	yes	6775.69
E-GEOD-124263	yes	4803.22
E-HCAD-11	yes	4276.19
E-MTAB-6701	yes	3667.85
E-HCAD-4	yes	3565.47
E-GEOD-134144	yes	2317.58
E-MTAB-8142	yes	2293.72
E-HCAD-24	yes	1708.64
E-MTAB-8884	yes	1239.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HES1, IFI16, PPARG, TFAP2A, TSC22D3

miRNA regulators (miRDB)

8 targeting CFD, 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-6744-5P	99.93	66.82	748
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-7158-5P	99.25	67.95	796
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-3674	97.01	68.86	1171
HSA-MIR-3907	96.76	65.04	662
HSA-MIR-3193	92.99	64.93	116
HSA-MIR-4707-3P	86.55	62.02	99

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 38)

• As adiponectin and adipsin levels in CSF did not correlate with their levels in plasma, it seems that there could be a secondary intrathecal synthesis of these adipocytokines in multiple sclerosis (PMID:19538214)
• increased serum levels in patients with seasonal allergic rhinitis (PMID:19699327)
• CFD may not play a major role in the genetic susceptibility to age-related macular degeneration. (PMID:21139680)
• crystal structure of C3bB at 4 A and complex with factor D at 3.5 A; data show how factor B binding to C3b forms open “activation” state of C3bB; Factor D binds open conformation of factor B through a site distant from the catalytic center (PMID:21205667)
• CFD regulates activation of the alternative complement pathway, which is implicated in age related macular degeneration pathogenesis. (PMID:22003108)
• Anti factor D Fab fragment inhibits FD proteolytic function by interfering with macromolecular substrate access rather than by inhibiting FD catalysis. (PMID:22362762)
• Increased activation of the alternative complement pathway in vitreous was controlled by disease stage and genetic variation in the complement pathway, supporting a role for complement activation in macular degeneration disease pathogenesis. (PMID:22930722)
• We demonstrate novel secretion of adipsin and ASP by placental Hofbauer cells. (PMID:23956345)
• Complement factor D (FD) is activated by its substrate through interactions outside the active site which lock the unbound native state into an ordered inactive conformation via the self-inhibitory loop in FD. (PMID:24598742)
• Data indicate that a urinary protein, adipsin, was significantly increased in patients with preeclampsia. (PMID:24958499)
• Study demonstrates that T2DM patients with beta cell failure are deficient in adipsin. (PMID:24995977)
• Overall adipsin levels among male asbestos industry workers were significantly higher than among control subjects. (PMID:25840635)
• our findings set up a novel mechanism for FABP4, adipsin and adiponectin through gut microbiota mediating expression in gut Paneth cells. (PMID:26687459)
• MASP-3 is the exclusive pro-factor D activator in resting blood: the lectin and the alternative complement pathways are fundamentally linked. (PMID:27535802)
• The strong association of PLIN1, CFD and ADIPOQ genes with adipogenesis prompted authors to study the influence the bone health status as evaluated by quantitative ultrasound (QUS) bone densitometer in a North Indian cohort. Overall, ADIPOQ (rs1501299 and rs3774261) and combined cluster of PLIN1 rs2304796 and rs2304795) and CFD (rs1683563) demonstrated correlation. (PMID:28189761)
• TZDs (pioglitazone, rosiglitazone, and ciglitazone) slow tumor cell growth in vitro and in vivo with decreases in cell proliferation and increases in PPARg and adipsin (PMID:28219679)
• disturbance of reciprocal relationships between adipsin and leptin in obesity is associated with the development of insulin resistance (PMID:28864895)
• The results suggested that elevated IL-17A and IL-9 expressions and decreased levels of adipsin and CCL11 were positively associated with adult asthma. (PMID:29138487)
• increased circulating levels of adipsin and decreased circulating levels of visfatin and adiponectin were independently associated with the increased risk of nonalcoholic fatty liver disease (PMID:30541001)
• Senescent dermal fibroblasts negatively influence fibroblast extracellular matrix-related gene expression (such as MMP1) partly via secretion of complement factor D. (PMID:31026383)
• High plasma adipsin levels are associated with mild cognitive impairment. (PMID:31651303)
• these data suggest that adipsin/C3a and DUSP26-directed therapies may represent a novel approach to achieve beta cell health to treat and prevent type 2 diabetes. (PMID:31700183)
• Direct activation of the alternative complement pathway by SARS-CoV-2 spike proteins is blocked by factor D inhibition. (PMID:32877502)
• The function of adipsin and C9 protein in the complement system in HIV-associated preeclampsia. (PMID:33881585)
• Adipsin promotes bone marrow adiposity by priming mesenchymal stem cells. (PMID:34155972)
• Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer-Simons syndrome). (PMID:34205507)
• Long-term physical activity modulates adipsin and ANGPTL4 serum levels, a potential link to exercise-induced metabolic changes. (PMID:34309331)
• Complement Factor D as a Strategic Target for Regulating the Alternative Complement Pathway. (PMID:34566967)
• Adipsin Serum Concentrations and Adipose Tissue Expression in People with Obesity and Type 2 Diabetes. (PMID:35216336)
• Plasma and aqueous levels of alarin and adipsin in patients with and without diabetic retinopathy. (PMID:35436912)
• Complement factor D as a predictor of Achilles tendon healing and long-term patient outcomes. (PMID:35596679)
• Elevated Adipsin and Reduced C5a Levels in the Maternal Serum and Follicular Fluid During Implantation Are Associated With Successful Pregnancy in Obese Women. (PMID:35909516)
• Serum and salivary adipsin levels and its association with insulin resistance in acne vulgaris patients. (PMID:36459421)
• The Role of Adipsin, Complement Factor D, in the Pathogenesis of Graves’ Orbitopathy. (PMID:37555734)
• Complement factor D regulates collagen type I expression and fibroblast migration to enhance human tendon repair and healing outcomes. (PMID:37744351)
• Adipsin in the pathogenesis of cardiovascular diseases. (PMID:38114042)
• Combinatorial Inhibition of Complement Factor D and BCL2 for Early-Onset Colorectal Cancer. (PMID:38479005)
• Adipose tissue-derived adipsin marks human aging in non-type 2 diabetes population. (PMID:39209774)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cfd	ENSDARG00000039579
mus_musculus	Cfd	ENSMUSG00000061780
rattus_norvegicus	Cfd	ENSRNOG00000033564

Paralogs (16): F7 (ENSG00000057593), F11 (ENSG00000088926), F9 (ENSG00000101981), HGFAC (ENSG00000109758), F10 (ENSG00000126218), KLK10 (ENSG00000129451), F12 (ENSG00000131187), C1RL (ENSG00000139178), C1R (ENSG00000159403), KLKB1 (ENSG00000164344), C1S (ENSG00000182326), PRSS55 (ENSG00000184647), CFI (ENSG00000205403), PRSS51 (ENSG00000253649), HP (ENSG00000257017), HPR (ENSG00000261701)

Protein

Protein identifiers

Complement factor D — P00746 (reviewed: P00746)

Alternative names: Adipsin, C3 convertase activator, Properdin factor D

All UniProt accessions (5): A0A8Q3WKV6, A0A8Q3WKW0, A0A8Q3WLE6, K7ERG9, P00746

UniProt curated annotations — full annotation on UniProt →

Function. Serine protease that initiates the alternative pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system. In contrast to other complement pathways (classical, lectin and GZMK) that are directly activated by pathogens or antigen-antibody complexes, the alternative complement pathway is initiated by the spontaneous hydrolysis of complement C3. The alternative complement pathway acts as an amplification loop that enhances complement activation by mediating the formation of C3 and C5 convertases. Activated CFD cleaves factor B (CFB) when the latter is complexed with complement C3b, activating the C3 convertase of the alternative pathway.

Subcellular location. Secreted.

Post-translational modifications. CFD is activated by the removal of 5 residues at the N-terminus, named activation peptide, by the MASP-3 isoform of MASP1.

Disease relevance. Complement factor D deficiency (CFDD) [MIM:613912] An immunologic disorder characterized by increased susceptibility to bacterial infections, particularly Neisseria infections, due to a defect in the alternative complement pathway. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Circulates in plasma in a mature but self-inhibited form. Activated by factor B (CFB), which displaces the self-inhibition loop. Associates with CFB complexed with complement C3b. Specifically inhibited by anti-factor D Fab fragment (AFD) antibody.

Domain organisation. The self-inhibition loop inhibits the serine protease activity in absence of factor B (CFB) substrate.

Similarity. Belongs to the peptidase S1 family.

RefSeq proteins (2): NP_001304264, NP_001919* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR043504

Pfam: PF00089

Enzyme classification (BRENDA):

• EC 3.4.21.46 — complement factor D (BRENDA: 9 organisms, 37 substrates, 121 inhibitors, 8 Km, 8 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
BENZYLOXYCARBONYL-LYS-THIOBENZYL ESTER	2.95–11.44	8

UniProt features (68 total): strand 19, sequence conflict 18, mutagenesis site 6, helix 5, disulfide bond 4, turn 4, sequence variant 3, active site 3, signal peptide 1, propeptide 1, chain 1, domain 1, region of interest 1, site 1

Structure

Experimental structures (PDB)

40 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5NAT	X-RAY DIFFRACTION	1.17
2XW9	X-RAY DIFFRACTION	1.2
5NAW	X-RAY DIFFRACTION	1.25
5MT0	X-RAY DIFFRACTION	1.29
5NB7	X-RAY DIFFRACTION	1.33
6FUH	X-RAY DIFFRACTION	1.37
6FUI	X-RAY DIFFRACTION	1.38
5FBE	X-RAY DIFFRACTION	1.43
5FBI	X-RAY DIFFRACTION	1.47
1BIO	X-RAY DIFFRACTION	1.5
6FUT	X-RAY DIFFRACTION	1.5
5NAR	X-RAY DIFFRACTION	1.55
5MT4	X-RAY DIFFRACTION	1.65
6FTY	X-RAY DIFFRACTION	1.67
6FTZ	X-RAY DIFFRACTION	1.67
5NB6	X-RAY DIFFRACTION	1.75
1DIC	X-RAY DIFFRACTION	1.8
4CBN	X-RAY DIFFRACTION	1.8
4CBO	X-RAY DIFFRACTION	1.8
6QMT	X-RAY DIFFRACTION	1.8
5FCK	X-RAY DIFFRACTION	1.86
5NBA	X-RAY DIFFRACTION	1.87
8DG6	X-RAY DIFFRACTION	1.99
1DST	X-RAY DIFFRACTION	2
1DSU	X-RAY DIFFRACTION	2
6QMR	X-RAY DIFFRACTION	2
1FDP	X-RAY DIFFRACTION	2.1
8D95	X-RAY DIFFRACTION	2.17
6FUG	X-RAY DIFFRACTION	2.21
8DEA	X-RAY DIFFRACTION	2.21

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00746-F1	91.19	0.80

Antibody-complex structures (SAbDab): 3 — 4D9R, 6VMJ, 6VMK

Functional residue map

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

Catalytic / active sites (4): 66 (charge relay system); 114 (charge relay system); 208 (charge relay system); 25–26 (cleavage; by masp-3 isoform of masp1)

Disulfide bonds (4): 148–214, 179–195, 204–229, 51–67

Mutagenesis-validated functional residues (6):

Position	Phenotype
158	abolished ability to cleave cfb.
182	abolished ability to cleave cfb.
208	abolished serine endopeptidase activity.
227	increased serine endopeptidase activity in absence of cfb, while decreased ability to cleave cfb.
227	abolished ability to cleave cfb.
228	abolished ability to cleave cfb.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-173736	Alternative complement activation
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 268 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, MCLACHLAN_DENTAL_CARIES_UP, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_SMOOTH_MUSCLE_CELL_DIFFERENTIATION, MODULE_45, HUMMERICH_BENIGN_SKIN_TUMOR_DN, HUMMERICH_MALIGNANT_SKIN_TUMOR_DN, GOBP_VASCULAR_ASSOCIATED_SMOOTH_MUSCLE_CELL_DIFFERENTIATION, MODULE_16, YORDY_RECIPROCAL_REGULATION_BY_ETS1_AND_SP100_DN, MARTINEZ_RB1_TARGETS_UP, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_COMPLEMENT_ACTIVATION

GO Biological Process (8): proteolysis (GO:0006508), complement activation (GO:0006956), complement activation, alternative pathway (GO:0006957), response to bacterium (GO:0009617), zymogen activation (GO:0031638), protein maturation (GO:0051604), immune system process (GO:0002376), innate immune response (GO:0045087)

GO Molecular Function (4): serine-type endopeptidase activity (GO:0004252), serine-type peptidase activity (GO:0008236), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), platelet alpha granule lumen (GO:0031093), secretory granule lumen (GO:0034774), extracellular exosome (GO:0070062), ficolin-1-rich granule lumen (GO:1904813)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Initial triggering of complement	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	2
immune effector process	1
activation of immune response	1
humoral immune response	1
protein activation cascade	1
complement activation	1
innate immune response	1
response to other organism	1
protein processing	1
gene expression	1
biological_process	1
immune response	1
defense response to symbiont	1
endopeptidase activity	1
serine-type peptidase activity	1
peptidase activity	1
serine hydrolase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cellular anatomical structure	1
platelet alpha granule	1
secretory granule lumen	1
secretory granule	1
cytoplasmic vesicle lumen	1
extracellular vesicle	1
intracellular organelle lumen	1
ficolin-1-rich granule	1

Protein interactions and networks

STRING

1594 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFD	C3	P01024	944
CFD	ADIPOQ	Q15848	860
CFD	RETN	Q9HD89	851
CFD	CFB	P00751	811
CFD	CFP	P27918	793
CFD	RETNLB	Q9BQ08	720
CFD	LEP	P41159	720
CFD	PPARG	P37231	622
CFD	FABP4	P15090	609
CFD	NAMPT	P43490	600
CFD	PCSK4	Q6UW60	593
CFD	INS	P01308	585
CFD	CD36	P16671	583
CFD	PCSK6	P29122	572
CFD	CEBPA	P49715	570

IntAct

5 interactions, top by confidence:

A	B	Type	Score
CFHR4	CFD	psi-mi:“MI:0915”(physical association)	0.400
	CD5L	psi-mi:“MI:0915”(physical association)	0.400
ALB	SH3BP5	psi-mi:“MI:0914”(association)	0.350
	CFD	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): CFD (Affinity Capture-RNA), CFD (Reconstituted Complex), CFD (Affinity Capture-MS), GZMM (Negative Genetic), CFD (Affinity Capture-MS)

ESM2 similar proteins: A6NIE9, O35164, O43240, P00746, P00770, P03953, P05981, P06870, P07288, P09582, P12323, P15944, P20151, P20160, P20231, P21845, P22457, P32038, P35034, P49862, P50343, P51124, P51779, P69526, P80015, Q00356, Q03238, Q05511, Q07276, Q14B24, Q15661, Q28773, Q3T0A3, Q3UP87, Q571E5, Q5R5E8, Q6GPI1, Q6IE59, Q7JIG6, Q80WM7

Diamond homologs: A7WPL7, O35164, O35205, O46683, O60259, O88780, P00746, P00752, P00760, P00761, P00762, P00763, P00764, P00770, P00772, P00773, P04187, P06870, P06871, P07146, P07288, P08311, P08426, P08882, P08883, P08884, P09582, P09650, P10144, P11032, P11033, P11034, P12323, P12544, P12788, P13366, P15119, P16049, P17977, P18291

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CFD	“up-regulates activity”	CFB	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	6
Uncertain significance	163
Likely benign	125
Benign	9

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
1411330	NC_000019.9:g.(?852329)(859764_?)del	Pathogenic
1412951	NM_001928.4(CFD):c.153C>A (p.Cys51Ter)	Pathogenic
1454250	NM_001928.4(CFD):c.285C>A (p.Tyr95Ter)	Pathogenic
16564	NM_001928.4(CFD):c.125C>A (p.Ser42Ter)	Pathogenic
16745	NM_001972.4(ELANE):c.377C>T (p.Ser126Leu)	Pathogenic
2011547	NM_001928.4(CFD):c.40G>T (p.Gly14Ter)	Pathogenic
2900060	NM_001928.4(CFD):c.132del (p.Gln44fs)	Pathogenic
3616379	NM_001928.4(CFD):c.444C>A (p.Cys148Ter)	Pathogenic
939547	NM_001972.4(ELANE):c.607G>C (p.Gly203Arg)	Pathogenic
1961905	NM_001928.4(CFD):c.213-2A>C	Likely pathogenic
2077091	NM_001928.4(CFD):c.358-259_461delinsCATTGA	Likely pathogenic
2417863	NM_001928.4(CFD):c.212+2T>G	Likely pathogenic
3779511	NM_001928.4(CFD):c.213-1G>C	Likely pathogenic
3779512	NM_001928.4(CFD):c.278_279dup (p.Leu94fs)	Likely pathogenic
636704	NM_001928.4(CFD):c.56-1G>C	Likely pathogenic

SpliceAI

936 predictions. Top by Δscore:

Variant	Effect	Δscore
19:860769:GACGC:G	donor_gain	1.0000
19:860772:GC:G	donor_gain	1.0000
19:860774:G:GG	donor_gain	1.0000
19:861698:GCT:G	acceptor_gain	1.0000
19:861952:GCAAG:G	donor_gain	1.0000
19:861957:G:GC	donor_loss	1.0000
19:861957:G:GG	donor_gain	1.0000
19:861958:T:A	donor_loss	1.0000
19:868857:CCTCA:C	donor_loss	1.0000
19:868858:CTCAC:C	donor_loss	1.0000
19:868859:TCACC:T	donor_loss	1.0000
19:868860:CACC:C	donor_loss	1.0000
19:868861:A:C	donor_loss	1.0000
19:868862:C:A	donor_loss	1.0000
19:868945:CC:C	acceptor_gain	1.0000
19:868946:CC:C	acceptor_gain	1.0000
19:868947:C:CC	acceptor_gain	1.0000
19:868948:T:C	acceptor_loss	1.0000
19:859750:G:GT	donor_gain	0.9900
19:860615:A:AG	acceptor_gain	0.9900
19:860615:AGC:A	acceptor_gain	0.9900
19:860616:G:GG	acceptor_gain	0.9900
19:860616:GC:G	acceptor_gain	0.9900
19:860616:GCG:G	acceptor_gain	0.9900
19:860616:GCGGC:G	acceptor_gain	0.9900
19:860769:G:GT	donor_gain	0.9900
19:861001:TACAG:T	donor_loss	0.9900
19:861002:ACAG:A	donor_loss	0.9900
19:861003:CAG:C	donor_loss	0.9900
19:861004:AG:A	donor_loss	0.9900

AlphaMissense

1609 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:861800:G:C	W153C	0.999
19:861800:G:T	W153C	0.999
19:861783:T:A	C148S	0.996
19:861784:G:C	C148S	0.996
19:863217:G:C	W247C	0.996
19:863217:G:T	W247C	0.996
19:861784:G:A	C148Y	0.995
19:861876:T:A	C179S	0.995
19:861877:G:A	C179Y	0.995
19:861877:G:C	C179S	0.995
19:861924:T:A	C195S	0.995
19:861925:G:C	C195S	0.995
19:860748:A:C	S63R	0.994
19:860750:C:A	S63R	0.994
19:860750:C:G	S63R	0.994
19:861798:T:A	W153R	0.993
19:861798:T:C	W153R	0.993
19:863096:A:T	D207V	0.993
19:860995:T:C	L116P	0.992
19:861785:C:G	C148W	0.992
19:861801:G:T	G154C	0.992
19:861951:T:A	C204S	0.992
19:861952:G:A	C204Y	0.992
19:861952:G:C	C204S	0.992
19:863102:G:A	G209E	0.991
19:863102:G:T	G209V	0.991
19:863161:T:A	C229S	0.991
19:863162:G:C	C229S	0.991
19:860989:A:T	D114V	0.990
19:861783:T:C	C148R	0.990

dbSNP variants (sampled 300 via entrez): RS1000024737 (19:862708 G>C,T), RS1000390956 (19:857908 AAAAG>A), RS1000422331 (19:857677 G>A), RS1000459917 (19:862573 C>T), RS1001226665 (19:862737 G>A), RS1001455379 (19:863999 A>G), RS1001481594 (19:863928 TAAA>T,TAA,TAAAA), RS1002939601 (19:859222 A>T), RS1003283121 (19:858132 G>A,T), RS1003893278 (19:862532 GA>G), RS1004056396 (19:863891 A>G), RS1004913555 (19:858966 G>A,T), RS1005292467 (19:859255 C>T), RS1005345419 (19:864080 C>A,T), RS1005463768 (19:860399 C>T)

Disease associations

OMIM: gene MIM:134350 | disease phenotypes: MIM:613912, MIM:162800, MIM:202700

GenCC curated gene-disease

Disease	Classification	Inheritance
recurrent Neisseria infections due to factor D deficiency	Strong	Autosomal recessive

Mondo (3): recurrent Neisseria infections due to factor D deficiency (MONDO:0013487), cyclic hematopoiesis (MONDO:0008090), neutropenia, severe congenital, 1, autosomal dominant (MONDO:0042490)

Orphanet (2): Recurrent Neisseria infections due to factor D deficiency (Orphanet:169467), Cyclic neutropenia (Orphanet:2686)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0002718	Recurrent bacterial infections
HP:0008338	Partial functional complement factor D deficiency

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90002386_93	High light scatter reticulocyte percentage of red cells	6.000000e-28
GCST90002405_570	Reticulocyte count	8.000000e-25

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
C565027	Complement Factor D Deficiency (supp.)
C536227	Cyclic neutropenia (supp.)
C565969	Neutropenia, Severe Congenital, Autosomal Dominant 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2176771 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 290 (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
CHEMBL4250860	DANICOPAN	4	290

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 3.4.21.46 Complement factor D

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
lampalizumab	Binding	10.7	pKi
danicopan	Inhibition	9.0	pKd
example 373 [WO2012093101]	Inhibition	9.0	pIC50
compound 2 [PMID: 28621538]	Inhibition	8.22	pIC50

Binding affinities (BindingDB)

1431 measured of 2892 human assays (2982 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[(1R)-3-[4-(4-amino-8-fluoro-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-1-(ethylamino)-3-oxopropyl]benzonitrile	IC50	1 nM	US-9452990: Complement pathway modulators and uses thereof
4-[(1R)-3-[4-(4-amino-8-fluoro-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-1-[(3-methyloxetan-3-yl)methylamino]-3-oxopropyl]benzonitrile	IC50	1 nM	US-9452990: Complement pathway modulators and uses thereof
(1R,3S,5R)-2-N-[1-carbamoyl-5-(cyanomethoxy)indol-3-yl]-3-N-[(3-chloro-2-fluorophenyl)methyl]-2-azabicyclo[3.1.0]hexane-2,3-dicarboxamide	IC50	1 nM	US-9085555: Complement pathway modulators and uses thereof
2-[1-carbamoyl-3-[[(2S,4R)-2-[(3-chloro-2-fluorophenyl)methylcarbamoyl]-4-fluoro-4-methylpyrrolidine-1-carbonyl]amino]indol-5-yl]oxyacetic acid	IC50	2 nM	US-9085555: Complement pathway modulators and uses thereof
(3S)-2-N-(1-carbamoylindol-3-yl)-3-N-[(3-chloro-2-fluorophenyl)methyl]-2-azabicyclo[3.1.0]hexane-2,3-dicarboxamide	IC50	3 nM	US-9085555: Complement pathway modulators and uses thereof
(2S,4R)-1-N-(1-carbamoyl-5-methoxyindol-3-yl)-2-N-[(3-chloro-2-fluorophenyl)methyl]-4-fluoropyrrolidine-1,2-dicarboxamide	IC50	3 nM	US-9085555: Complement pathway modulators and uses thereof
methyl 2-[1-carbamoyl-3-[[(2S,4R)-2-[(3-chloro-2-fluorophenyl)methylcarbamoyl]-4-fluoro-4-methylpyrrolidine-1-carbonyl]amino]indol-5-yl]oxyacetate	IC50	3 nM	US-9085555: Complement pathway modulators and uses thereof
(1R,3S,5R)-2-N-(1-carbamoyl-5-hydroxyindol-3-yl)-3-N-[(3-chloro-2-fluorophenyl)methyl]-2-azabicyclo[3.1.0]hexane-2,3-dicarboxamide	IC50	3 nM	US-9085555: Complement pathway modulators and uses thereof
2-[1-carbamoyl-3-[[(1R,3S,5R)-3-[(3-chloro-2-fluorophenyl)methylcarbamoyl]-2-azabicyclo[3.1.0]hexane-2-carbonyl]amino]indol-5-yl]oxyacetic acid	IC50	3 nM	US-9085555: Complement pathway modulators and uses thereof
1-[2-[(1R,3S,5R)-3-[(3-chloro-2-fluorophenyl)methylcarbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxoethyl]indazole-3-carboxamide	IC50	3 nM	US-9085555: Complement pathway modulators and uses thereof
1-[2-[(2S,3S,4S)-2-[(3-chloro-2-fluorophenyl)methylcarbamoyl]-4-fluoro-3-methoxypyrrolidin-1-yl]-2-oxoethyl]-5-ethylpyrazolo[5,4-c]pyridine-3-carboxamide	IC50	3 nM	US-9085555: Complement pathway modulators and uses thereof
1-[2-[(1R,3S,5R)-3-[(6-bromo-2-pyridinyl)carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxoethyl]-5-ethylpyrazolo[5,4-c]pyridine-3-carboxamide	IC50	3 nM	US-9085555: Complement pathway modulators and uses thereof
(1R,3S,5R)-2-[2-(3-acetylindazol-1-yl)acetyl]-N-(6-bromopyrazin-2-yl)-2-azabicyclo[3.1.0]hexane-3-carboxamide	IC50	3 nM	US-9085555: Complement pathway modulators and uses thereof
4-[(1R)-3-[4-(4-amino-8-fluoro-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-3-oxo-1-(propan-2-ylamino)propyl]benzonitrile	IC50	3 nM	US-9452990: Complement pathway modulators and uses thereof
(2R)-4-[4-(4-amino-8-fluoro-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-N-ethyl-2-(4-fluorophenyl)-4-oxobutanamide	IC50	3 nM	US-9452990: Complement pathway modulators and uses thereof
(1R,3S,5R)-2-[2-[3-acetyl-5-[(1-methyl-1,2,4-triazol-3-yl)methoxy]indazol-1-yl]acetyl]-N-[(1R)-1-[(1R)-2,2-dichlorocyclopropyl]ethyl]-2-azabicyclo[3.1.0]hexane-3-carboxamide	IC50	3 nM	US-9468661: Pyrrolidine derivatives and their use as complement pathway modulators
(1R,3S,5R)-2-[2-[3-acetyl-5-[(5-methyl-1H-pyrazol-3-yl)methoxy]indazol-1-yl]acetyl]-N-[(1R)-1-[(1R)-2,2-dichlorocyclopropyl]ethyl]-2-azabicyclo[3.1.0]hexane-3-carboxamide	IC50	3 nM	US-9468661: Pyrrolidine derivatives and their use as complement pathway modulators
(1R,3S,5R)-2-[2-[3-acetyl-5-(pyrimidin-2-ylmethoxy)indazol-1-yl]acetyl]-N-[[(1S)-2,2-dichloro-3-methylcyclopropyl]methyl]-2-azabicyclo[3.1.0]hexane-3-carboxamide	IC50	3 nM	US-9468661: Pyrrolidine derivatives and their use as complement pathway modulators
tert-butyl 2-[1-carbamoyl-3-[[(1R,3S,5R)-3-[(3-chloro-2-fluorophenyl)methylcarbamoyl]-2-azabicyclo[3.1.0]hexane-2-carbonyl]amino]indol-6-yl]acetate	IC50	3 nM	US-9085555: Complement pathway modulators and uses thereof
(1R,3S,5R)-2-N-(1-acetylindol-3-yl)-3-N-[(1S)-1-(3-chloro-2-fluorophenyl)-2-hydroxyethyl]-2-azabicyclo[3.1.0]hexane-2,3-dicarboxamide	IC50	4 nM	US-9085555: Complement pathway modulators and uses thereof
(3S)-2-N-(1-carbamoyl-5-methoxyindol-3-yl)-3-N-[(3-chloro-2-fluorophenyl)methyl]-2-azabicyclo[3.1.0]hexane-2,3-dicarboxamide	IC50	4 nM	US-9085555: Complement pathway modulators and uses thereof
ethyl 2-[1-carbamoyl-3-[[(1R,3S,5R)-3-[(3-chloro-2-fluorophenyl)methylcarbamoyl]-2-azabicyclo[3.1.0]hexane-2-carbonyl]amino]indol-5-yl]acetate	IC50	4 nM	US-9085555: Complement pathway modulators and uses thereof
(2S,4R)-1-N-[1-carbamoyl-5-(2-hydroxyethoxy)indol-3-yl]-2-N-[(3-chloro-2-fluorophenyl)methyl]-4-fluoro-4-methylpyrrolidine-1,2-dicarboxamide	IC50	4 nM	US-9085555: Complement pathway modulators and uses thereof
1-[2-[(1R,3S,5R)-3-[(6-bromo-2-pyridinyl)carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxoethyl]-5-methylpyrazolo[5,4-c]pyridine-3-carboxamide	IC50	4 nM	US-9085555: Complement pathway modulators and uses thereof
1-[2-[(1R,3S,5R)-3-[(6-bromo-2-pyridinyl)carbamoyl]-5-methyl-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxoethyl]indazole-3-carboxamide	IC50	4 nM	US-9085555: Complement pathway modulators and uses thereof
(1R,3S,5R)-2-[2-[3-acetyl-5-(pyrimidin-2-ylmethoxy)indazol-1-yl]acetyl]-N-(6-bromo-2-pyridinyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide	IC50	4 nM	US-9085555: Complement pathway modulators and uses thereof
1-[2-[(1R,3S,5R)-3-[(6-bromo-2-pyridinyl)carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxoethyl]-6-chloroindazole-3-carboxamide	IC50	4 nM	US-9085555: Complement pathway modulators and uses thereof
(2S,4R)-2-N-(6-bromo-2-pyridinyl)-1-N-(1-carbamoylindol-3-yl)-4-fluoropyrrolidine-1,2-dicarboxamide	IC50	4 nM	US-9085555: Complement pathway modulators and uses thereof
4-[(1R)-3-[4-(4-amino-8-fluoro-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-1-(methylamino)-3-oxopropyl]benzonitrile	IC50	4 nM	US-9452990: Complement pathway modulators and uses thereof
(3R)-1-[4-(4-amino-8-fluoro-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-3-(cyclopropylmethylamino)-3-thiophen-3-ylpropan-1-one	IC50	4 nM	US-9452990: Complement pathway modulators and uses thereof
6-chloro-1-[2-[(1R,3S,5R)-3-[[(1R)-1-[(1R)-2,2-dichlorocyclopropyl]ethyl]carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxoethyl]indazole-3-carboxamide	IC50	4 nM	US-9468661: Pyrrolidine derivatives and their use as complement pathway modulators
(1R,3S,5R)-2-[2-[3-acetyl-6-methyl-5-(pyrimidin-2-ylmethoxy)indazol-1-yl]acetyl]-N-[(1R)-1-[(1R)-2,2-dichlorocyclopropyl]ethyl]-2-azabicyclo[3.1.0]hexane-3-carboxamide	IC50	4 nM	US-9468661: Pyrrolidine derivatives and their use as complement pathway modulators
(1R,3S,5R)-2-[2-[3-acetyl-5-[(1-methylpyrazol-3-yl)methoxy]indazol-1-yl]acetyl]-N-[(1R)-1-[(1R)-2,2-dichlorocyclopropyl]ethyl]-2-azabicyclo[3.1.0]hexane-3-carboxamide	IC50	4 nM	US-9468661: Pyrrolidine derivatives and their use as complement pathway modulators
(3S)-2-N-[1-carbamoyl-5-(2-methoxyethoxy)indol-3-yl]-3-N-[(3-chloro-2-fluorophenyl)methyl]-2-azabicyclo[3.1.0]hexane-2,3-dicarboxamide	IC50	5 nM	US-9085555: Complement pathway modulators and uses thereof
(3S)-2-N-(1-carbamoyl-5-fluoroindol-3-yl)-3-N-[(3-chloro-2-fluorophenyl)methyl]-2-azabicyclo[3.1.0]hexane-2,3-dicarboxamide	IC50	5 nM	US-9085555: Complement pathway modulators and uses thereof
(3S)-2-N-(1-carbamoylindol-3-yl)-3-N-[(3-chloro-2-fluorophenyl)methyl]-3,4-dihydropyrazole-2,3-dicarboxamide	IC50	5 nM	US-9085555: Complement pathway modulators and uses thereof
(1R,3S,5R)-2-N-[1-carbamoyl-5-(2-hydroxyethoxy)indol-3-yl]-3-N-[(3-chloro-2-fluorophenyl)methyl]-2-azabicyclo[3.1.0]hexane-2,3-dicarboxamide	IC50	5 nM	US-9085555: Complement pathway modulators and uses thereof
(2S,3S,4S)-1-[2-[3-acetyl-5-(pyrimidin-2-ylmethoxy)indazol-1-yl]acetyl]-4-fluoro-N-[2-fluoro-3-(trifluoromethoxy)phenyl]-3-methoxypyrrolidine-2-carboxamide	IC50	5 nM	US-9085555: Complement pathway modulators and uses thereof
1-[2-[(1R,3S,5R)-3-[[3-(2-chlorophenyl)-2-fluorophenyl]carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxoethyl]pyrazolo[5,4-c]pyridine-3-carboxamide	IC50	5 nM	US-9085555: Complement pathway modulators and uses thereof
1-[2-[(1R,3S,5R)-3-[(6-bromo-2-pyridinyl)carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxoethyl]-5,7-dimethylpyrazolo[5,4-c]pyridine-3-carboxamide	IC50	5 nM	US-9085555: Complement pathway modulators and uses thereof
1-[2-[(1R,3S,5R)-3-[(6-bromo-2-pyridinyl)carbamoyl]-5-methyl-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxoethyl]-5-methylpyrazolo[5,4-c]pyridine-3-carboxamide	IC50	5 nM	US-9085555: Complement pathway modulators and uses thereof
1-[2-[(2S,3S,4S)-2-[(6-bromo-2-pyridinyl)carbamoyl]-4-fluoro-3-methoxypyrrolidin-1-yl]-2-oxoethyl]indazole-3-carboxamide	IC50	5 nM	US-9085555: Complement pathway modulators and uses thereof
(1R,3S,5R)-3-N-(6-bromo-2-pyridinyl)-2-N-(1-carbamoylindol-3-yl)-2-azabicyclo[3.1.0]hexane-2,3-dicarboxamide	IC50	5 nM	US-9085555: Complement pathway modulators and uses thereof
(1R,3S,5R)-2-[2-[3-acetyl-5-(1,3-thiazol-2-ylmethoxy)indazol-1-yl]acetyl]-N-[[(1R)-2,2-dichlorocyclopropyl]methyl]-2-azabicyclo[3.1.0]hexane-3-carboxamide	IC50	5 nM	US-9468661: Pyrrolidine derivatives and their use as complement pathway modulators
methyl 2-[1-carbamoyl-3-[[(3S)-3-[(3-chloro-2-fluorophenyl)methylcarbamoyl]-2-azabicyclo[3.1.0]hexane-2-carbonyl]amino]indol-5-yl]oxyacetate	IC50	6 nM	US-9085555: Complement pathway modulators and uses thereof
(2S)-3-N-(1-carbamoylindol-3-yl)-2-N-[(3-chloro-2-fluorophenyl)methyl]-1,3-thiazolidine-2,3-dicarboxamide	IC50	6 nM	US-9085555: Complement pathway modulators and uses thereof
(1R,3S,5R)-2-N-(1-carbamoylindol-3-yl)-3-N-[(1S)-1-(3-chloro-2-fluorophenyl)-2-hydroxyethyl]-2-azabicyclo[3.1.0]hexane-2,3-dicarboxamide	IC50	6 nM	US-9085555: Complement pathway modulators and uses thereof
(1R,3S,5R)-2-[2-[3-acetyl-5-(pyrimidin-2-ylmethoxy)indol-1-yl]acetyl]-N-[(3-chloro-2-fluorophenyl)methyl]-2-azabicyclo[3.1.0]hexane-3-carboxamide	IC50	6 nM	US-9085555: Complement pathway modulators and uses thereof
1-[2-[(1R,3S,5R)-3-[[(1R)-1-(3-chloro-2-fluorophenyl)ethyl]carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxoethyl]-7-methylpyrazolo[5,4-c]pyridine-3-carboxamide	IC50	6 nM	US-9085555: Complement pathway modulators and uses thereof
1-[2-[(1R,3S,5R)-3-[(3-chloro-2-fluorophenyl)methylcarbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxoethyl]-5-cyclopropylpyrazolo[3,4-c]pyridine-3-carboxamide	IC50	6 nM	US-9085555: Complement pathway modulators and uses thereof

ChEMBL bioactivities

1944 potent at pChembl≥5 of 2040 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	IC50	1	nM	CHEMBL2180765
9.00	IC50	1	nM	CHEMBL4114217
9.00	IC50	1	nM	CHEMBL4106993
8.70	IC50	2	nM	CHEMBL2180764
8.70	IC50	2	nM	CHEMBL3109655
8.52	IC50	3	nM	CHEMBL2180766
8.52	IC50	3	nM	CHEMBL3109654
8.52	IC50	3	nM	CHEMBL3668673
8.52	IC50	3	nM	CHEMBL3673724
8.52	IC50	3	nM	CHEMBL3673750
8.52	IC50	3	nM	CHEMBL3673802
8.52	IC50	3	nM	CHEMBL3673804
8.52	IC50	3	nM	CHEMBL3678905
8.52	IC50	3	nM	CHEMBL3678910
8.52	IC50	3	nM	CHEMBL3678945
8.52	IC50	3	nM	CHEMBL3683717
8.52	IC50	3	nM	CHEMBL4107243
8.52	IC50	3	nM	CHEMBL4113469
8.52	IC50	3	nM	CHEMBL4115620
8.52	IC50	3	nM	CHEMBL4106731
8.52	IC50	3	nM	CHEMBL4111856
8.52	IC50	3	nM	CHEMBL4535197
8.40	IC50	4	nM	CHEMBL3668636
8.40	IC50	4	nM	CHEMBL3673732
8.40	IC50	4	nM	CHEMBL3673738
8.40	IC50	4	nM	CHEMBL3673812
8.40	IC50	4	nM	CHEMBL3678944
8.40	IC50	4	nM	CHEMBL3683720
8.40	IC50	4	nM	CHEMBL3683724
8.40	IC50	4	nM	CHEMBL3683725
8.40	IC50	4	nM	CHEMBL3683739
8.40	IC50	4	nM	CHEMBL4108959
8.40	IC50	4	nM	CHEMBL4111681
8.40	IC50	4	nM	CHEMBL4112203
8.40	IC50	4	nM	CHEMBL4114056
8.40	IC50	4	nM	CHEMBL4111206
8.40	IC50	4	nM	DANICOPAN
8.40	IC50	4	nM	CHEMBL4246585
8.30	IC50	5	nM	CHEMBL3668669
8.30	IC50	5	nM	CHEMBL3673726
8.30	IC50	5	nM	CHEMBL3673793
8.30	IC50	5	nM	CHEMBL3673808
8.30	IC50	5	nM	CHEMBL3678852
8.30	IC50	5	nM	CHEMBL3678898
8.30	IC50	5	nM	CHEMBL3683717
8.30	IC50	5	nM	CHEMBL3683719
8.30	IC50	5	nM	CHEMBL3965664
8.30	IC50	5	nM	CHEMBL3683730
8.30	IC50	5	nM	CHEMBL3683737
8.30	IC50	5	nM	CHEMBL4114574

PubChem BioAssay actives

171 with measured affinity, of 277 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
Danicopan	1393250: Binding affinity to human factor D by SPR analysis	kd	0.0010	uM
(1R,3S,5R)-2-N-[1-carbamoyl-5-(cyanomethoxy)indol-3-yl]-3-N-[(3-chloro-2-fluorophenyl)methyl]-2-azabicyclo[3.1.0]hexane-2,3-dicarboxamide	704668: Inhibition of recombinant human complement factor D after 1 hr	ic50	0.0010	uM
2-[1-carbamoyl-3-[[(2S,4R)-2-[(3-chloro-2-fluorophenyl)methylcarbamoyl]-4-fluoro-4-methylpyrrolidine-1-carbonyl]amino]indol-5-yl]oxyacetic acid	704668: Inhibition of recombinant human complement factor D after 1 hr	ic50	0.0020	uM
1-[2-[(1R,3S,5R)-3-[(6-bromo-2-pyridinyl)carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxoethyl]-5-(fluoromethyl)pyrazolo[5,4-c]pyridine-3-carboxamide	1065276: Inhibition of recombinant human factor D expressed in Escherichia coli using Z-Lys-thiobenzyl and 2,4-dinitrobenzenesulfonyl-fluoresceine as substrate preincubated for 1 hr followed by substrate addition by spectrofluorimetric analysis	ic50	0.0020	uM
2-[2-[[3-[3-[(1S)-1-amino-2-hydroxyethyl]phenyl]-5-bromophenyl]methoxy]phenyl]acetic acid	1595848: Inhibition of 2-((1E,3E,5E)-5-(1-(6-((((3S,5S)-1-((1-carbamoyl-1H-indol-3-yl)carbamoyl)-5-((3-chloro-2-fluorobenzyl)carbamoyl)-3-fluoropyrrolidin-3-yl)methyl)amino)-6-oxohexyl)-3,3-dimethyl-5-sulfoindolin-2-ylidene)penta-1,3-dien-1-yl)-1-ethyl-3,3-dimethyl-5-sulfo-3H-indol-1-ium binding to biotin-labeled recombinant human FD expressed in Escherichia coli measured after 2 hrs by TR-FRET assay	ic50	0.0030	uM
tert-butyl 2-[1-carbamoyl-3-[[(1R,3S,5R)-3-[(3-chloro-2-fluorophenyl)methylcarbamoyl]-2-azabicyclo[3.1.0]hexane-2-carbonyl]amino]indol-6-yl]acetate	704668: Inhibition of recombinant human complement factor D after 1 hr	ic50	0.0030	uM
1-[2-[(1R,3S,5R)-3-[(6-iodo-2-pyridinyl)carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxoethyl]indazole-3-carboxamide	1065276: Inhibition of recombinant human factor D expressed in Escherichia coli using Z-Lys-thiobenzyl and 2,4-dinitrobenzenesulfonyl-fluoresceine as substrate preincubated for 1 hr followed by substrate addition by spectrofluorimetric analysis	ic50	0.0030	uM
2-[2-[[3-[3-[(1S)-1-amino-2-hydroxyethyl]phenyl]-5-(hydroxymethyl)phenyl]methoxy]phenyl]acetic acid	1393249: Inhibition of human factor D expressed in Escherichia coli using CVF-FB as substrate assessed as decrease in formation of factor B cleavage product Ba after 1 hr by ELISA	ic50	0.0040	uM
1-[2-[(1R,3S,5R)-3-[(6-bromo-2-pyridinyl)carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxoethyl]indazole-3-carboxamide	1445601: Inhibition of recombinant human complement factor D catalytic domain using Z-Lys-thiobenzylester as substrate preincubated for 1 hr followed by substrate addition by 2,4-dinitrobenzenesulfonyl-2,7-desmethyl-fluorecein probe based spectrofluorimetric assay	ic50	0.0050	uM
(1R,3S,5R)-3-N-(6-bromo-2-pyridinyl)-2-N-(1-carbamoylindol-3-yl)-2-azabicyclo[3.1.0]hexane-2,3-dicarboxamide	1445601: Inhibition of recombinant human complement factor D catalytic domain using Z-Lys-thiobenzylester as substrate preincubated for 1 hr followed by substrate addition by 2,4-dinitrobenzenesulfonyl-2,7-desmethyl-fluorecein probe based spectrofluorimetric assay	ic50	0.0060	uM
1-[2-[(1R,3S,5R)-3-[[(1S)-1-(3-chloro-2-fluorophenyl)ethyl]carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxoethyl]pyrazolo[5,4-b]pyridine-3-carboxamide	1674158: Inhibition of CFD in 10% human serum assessed as reduction in alternate complement pathway-mediated hemolysis incubated for 1 hr	ic50	0.0060	uM
1-[2-[(1R,3S,5R)-3-[[(1R)-1-(3-chloro-2-fluorophenyl)ethyl]carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxoethyl]pyrazolo[5,4-c]pyridine-3-carboxamide	1802178: SPR Binding Affinity Assay (Single Cycle) from Article 10.1038/nchembio.2208: “Small-molecule factor D inhibitors targeting the alternative complement pathway.”	kd	0.0060	uM
5,7-dimethyl-1-[2-oxo-2-[(1R,3S,5R)-3-[[6-(trifluoromethyl)-2-pyridinyl]carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]ethyl]pyrazolo[5,4-c]pyridine-3-carboxamide	1065276: Inhibition of recombinant human factor D expressed in Escherichia coli using Z-Lys-thiobenzyl and 2,4-dinitrobenzenesulfonyl-fluoresceine as substrate preincubated for 1 hr followed by substrate addition by spectrofluorimetric analysis	ic50	0.0060	uM
2-[2-[[3-[3-[(1S)-1-amino-2-hydroxyethyl]phenyl]-5-(2-hydroxypropan-2-yl)phenyl]methoxy]phenyl]acetic acid	1595848: Inhibition of 2-((1E,3E,5E)-5-(1-(6-((((3S,5S)-1-((1-carbamoyl-1H-indol-3-yl)carbamoyl)-5-((3-chloro-2-fluorobenzyl)carbamoyl)-3-fluoropyrrolidin-3-yl)methyl)amino)-6-oxohexyl)-3,3-dimethyl-5-sulfoindolin-2-ylidene)penta-1,3-dien-1-yl)-1-ethyl-3,3-dimethyl-5-sulfo-3H-indol-1-ium binding to biotin-labeled recombinant human FD expressed in Escherichia coli measured after 2 hrs by TR-FRET assay	ic50	0.0080	uM
2-[2-[[3-[3-(aminomethyl)phenyl]phenyl]methoxy]phenyl]acetic acid	1595848: Inhibition of 2-((1E,3E,5E)-5-(1-(6-((((3S,5S)-1-((1-carbamoyl-1H-indol-3-yl)carbamoyl)-5-((3-chloro-2-fluorobenzyl)carbamoyl)-3-fluoropyrrolidin-3-yl)methyl)amino)-6-oxohexyl)-3,3-dimethyl-5-sulfoindolin-2-ylidene)penta-1,3-dien-1-yl)-1-ethyl-3,3-dimethyl-5-sulfo-3H-indol-1-ium binding to biotin-labeled recombinant human FD expressed in Escherichia coli measured after 2 hrs by TR-FRET assay	ic50	0.0080	uM
2-[2-[[3-[3-[(1S)-1-amino-2-hydroxyethyl]phenyl]-5-(methoxymethyl)phenyl]methoxy]phenyl]acetic acid	1595848: Inhibition of 2-((1E,3E,5E)-5-(1-(6-((((3S,5S)-1-((1-carbamoyl-1H-indol-3-yl)carbamoyl)-5-((3-chloro-2-fluorobenzyl)carbamoyl)-3-fluoropyrrolidin-3-yl)methyl)amino)-6-oxohexyl)-3,3-dimethyl-5-sulfoindolin-2-ylidene)penta-1,3-dien-1-yl)-1-ethyl-3,3-dimethyl-5-sulfo-3H-indol-1-ium binding to biotin-labeled recombinant human FD expressed in Escherichia coli measured after 2 hrs by TR-FRET assay	ic50	0.0100	uM
1-[2-[(1R,3S,5R)-3-[(3-bromo-2-fluorophenyl)carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxoethyl]indazole-3-carboxamide	1445601: Inhibition of recombinant human complement factor D catalytic domain using Z-Lys-thiobenzylester as substrate preincubated for 1 hr followed by substrate addition by 2,4-dinitrobenzenesulfonyl-2,7-desmethyl-fluorecein probe based spectrofluorimetric assay	ic50	0.0100	uM
2-[2-[[3-[3-[(1S)-1-amino-2-hydroxyethyl]phenyl]phenyl]methoxy]phenyl]acetic acid	1595848: Inhibition of 2-((1E,3E,5E)-5-(1-(6-((((3S,5S)-1-((1-carbamoyl-1H-indol-3-yl)carbamoyl)-5-((3-chloro-2-fluorobenzyl)carbamoyl)-3-fluoropyrrolidin-3-yl)methyl)amino)-6-oxohexyl)-3,3-dimethyl-5-sulfoindolin-2-ylidene)penta-1,3-dien-1-yl)-1-ethyl-3,3-dimethyl-5-sulfo-3H-indol-1-ium binding to biotin-labeled recombinant human FD expressed in Escherichia coli measured after 2 hrs by TR-FRET assay	ic50	0.0120	uM
(1R,3S,5R)-2-N-(1-carbamoylindol-3-yl)-3-N-[2-fluoro-3-(trifluoromethoxy)phenyl]-2-azabicyclo[3.1.0]hexane-2,3-dicarboxamide	1445601: Inhibition of recombinant human complement factor D catalytic domain using Z-Lys-thiobenzylester as substrate preincubated for 1 hr followed by substrate addition by 2,4-dinitrobenzenesulfonyl-2,7-desmethyl-fluorecein probe based spectrofluorimetric assay	ic50	0.0120	uM
(1R,3S,5R)-2-N-(1-carbamoylindol-3-yl)-3-N-[6-(trifluoromethyl)-2-pyridinyl]-2-azabicyclo[3.1.0]hexane-2,3-dicarboxamide	1445601: Inhibition of recombinant human complement factor D catalytic domain using Z-Lys-thiobenzylester as substrate preincubated for 1 hr followed by substrate addition by 2,4-dinitrobenzenesulfonyl-2,7-desmethyl-fluorecein probe based spectrofluorimetric assay	ic50	0.0140	uM
2-[2-[[3-[3-[(1S)-1-amino-2-hydroxyethyl]phenyl]-5-(propan-2-ylamino)phenyl]methoxy]phenyl]acetic acid	1595848: Inhibition of 2-((1E,3E,5E)-5-(1-(6-((((3S,5S)-1-((1-carbamoyl-1H-indol-3-yl)carbamoyl)-5-((3-chloro-2-fluorobenzyl)carbamoyl)-3-fluoropyrrolidin-3-yl)methyl)amino)-6-oxohexyl)-3,3-dimethyl-5-sulfoindolin-2-ylidene)penta-1,3-dien-1-yl)-1-ethyl-3,3-dimethyl-5-sulfo-3H-indol-1-ium binding to biotin-labeled recombinant human FD expressed in Escherichia coli measured after 2 hrs by TR-FRET assay	ic50	0.0150	uM
(1R,3S,5R)-2-[2-(3-acetylindazol-1-yl)acetyl]-N-(6-bromo-2-pyridinyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide	1445601: Inhibition of recombinant human complement factor D catalytic domain using Z-Lys-thiobenzylester as substrate preincubated for 1 hr followed by substrate addition by 2,4-dinitrobenzenesulfonyl-2,7-desmethyl-fluorecein probe based spectrofluorimetric assay	ic50	0.0150	uM
1-[2-[(1R,3S,5R)-3-[(6-bromo-2-pyridinyl)carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxoethyl]pyrazolo[5,4-b]pyridine-3-carboxamide	1325988: Binding affinity to recombinant human C-terminal 6His-tagged/biotinylated complement factor D (26 to 253 residues) expressed in Sf9 insect cells by biolayer interferometry method	kd	0.0170	uM
1-[2-[[2-[(3-chloro-2-fluorophenyl)methylamino]-2-oxoethyl]-cyclopropylamino]-2-oxoethyl]-5-[[methyl-(1-methylpiperidin-4-yl)carbamoyl]amino]indazole-3-carboxamide	1918209: Inhibition of human complement factor D using Z-L-Lys-SBzl hydrochloride as substrate preincubated for 15 mins followed by substrate addition and measured by colorimetric method based esterolytic assay	ki	0.0185	uM
(2S)-N-(6-bromo-2-pyridinyl)-3-[2-(3-carbamoylpyrazolo[5,4-b]pyridin-1-yl)acetyl]-1,3-thiazolidine-2-carboxamide	1325988: Binding affinity to recombinant human C-terminal 6His-tagged/biotinylated complement factor D (26 to 253 residues) expressed in Sf9 insect cells by biolayer interferometry method	kd	0.0188	uM
(1R,3S,5R)-N-(6-bromo-2-pyridinyl)-2-(2-indazol-1-ylacetyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide	1325992: Inhibition of human serum factor D-mediated complement activation in rabbit erythrocytes assessed as reduction in rabbit erythrocyte hemolysis preincubated with human serum for 15 mins followed by addition of rabbit erythrocytes and Mg-EGTA measured after 30 mins	ic50	0.0190	uM
2-[2-[[6-[3-(aminomethyl)phenyl]pyridine-2-carbonyl]amino]phenyl]acetic acid	1595853: Inhibition of FD-mediated alternative complementation pathway in 50% human whole blood assessed as reduction in zymosan-induced membrane-attack complex formation preincubated for 15 mins followed by zymosan stimulation and measured after 40 mins by ELISA	ic50	0.0200	uM
2-[2-[[3-[3-(2-amino-2-oxoethyl)-2-fluorophenyl]-5-(1-methylpyrazol-4-yl)phenyl]methoxy]phenyl]acetic acid	1393253: Displacement of Cy5 from recombinant human biotin labeled factor D expressed in Escherichia coli after 2 hrs by TR-FRET assay	ic50	0.0230	uM
(1R,3S,5R)-2-N-(1-carbamoylindol-3-yl)-3-N-[2-fluoro-3-(trifluoromethyl)phenyl]-2-azabicyclo[3.1.0]hexane-2,3-dicarboxamide	1445601: Inhibition of recombinant human complement factor D catalytic domain using Z-Lys-thiobenzylester as substrate preincubated for 1 hr followed by substrate addition by 2,4-dinitrobenzenesulfonyl-2,7-desmethyl-fluorecein probe based spectrofluorimetric assay	ic50	0.0230	uM
2-[2-[[3-[3-[(1R)-1-aminoethyl]phenyl]phenyl]methoxy]phenyl]acetic acid	1595848: Inhibition of 2-((1E,3E,5E)-5-(1-(6-((((3S,5S)-1-((1-carbamoyl-1H-indol-3-yl)carbamoyl)-5-((3-chloro-2-fluorobenzyl)carbamoyl)-3-fluoropyrrolidin-3-yl)methyl)amino)-6-oxohexyl)-3,3-dimethyl-5-sulfoindolin-2-ylidene)penta-1,3-dien-1-yl)-1-ethyl-3,3-dimethyl-5-sulfo-3H-indol-1-ium binding to biotin-labeled recombinant human FD expressed in Escherichia coli measured after 2 hrs by TR-FRET assay	ic50	0.0250	uM
3-carbamoyl-1-[2-[[2-[(3-chloro-2-fluorophenyl)methylamino]-2-oxoethyl]-cyclopropylamino]-2-oxoethyl]indazole-6-carboxylic acid	1918209: Inhibition of human complement factor D using Z-L-Lys-SBzl hydrochloride as substrate preincubated for 15 mins followed by substrate addition and measured by colorimetric method based esterolytic assay	ic50	0.0270	uM
1-[2-[[2-[(3-chloro-2-fluorophenyl)methylamino]-2-oxoethyl]-cyclopropylamino]-2-oxoethyl]-5-[(4-cyclopropylpiperazine-1-carbonyl)amino]indazole-3-carboxamide	1918209: Inhibition of human complement factor D using Z-L-Lys-SBzl hydrochloride as substrate preincubated for 15 mins followed by substrate addition and measured by colorimetric method based esterolytic assay	ic50	0.0280	uM
2-[2-[[3-[3-[(1R)-1-amino-3-hydroxypropyl]phenyl]phenyl]methoxy]phenyl]acetic acid	1595848: Inhibition of 2-((1E,3E,5E)-5-(1-(6-((((3S,5S)-1-((1-carbamoyl-1H-indol-3-yl)carbamoyl)-5-((3-chloro-2-fluorobenzyl)carbamoyl)-3-fluoropyrrolidin-3-yl)methyl)amino)-6-oxohexyl)-3,3-dimethyl-5-sulfoindolin-2-ylidene)penta-1,3-dien-1-yl)-1-ethyl-3,3-dimethyl-5-sulfo-3H-indol-1-ium binding to biotin-labeled recombinant human FD expressed in Escherichia coli measured after 2 hrs by TR-FRET assay	ic50	0.0300	uM
1-[2-[[2-[(3-chloro-2-fluorophenyl)methylamino]-2-oxoethyl]-cyclopropylamino]-2-oxoethyl]-5-[[4-[(4-fluorophenyl)methyl]piperazine-1-carbonyl]amino]indazole-3-carboxamide	1918209: Inhibition of human complement factor D using Z-L-Lys-SBzl hydrochloride as substrate preincubated for 15 mins followed by substrate addition and measured by colorimetric method based esterolytic assay	ic50	0.0300	uM
1-[2-[(1R,3S,5R)-3-[[(1S)-1-(3-chloro-2-fluorophenyl)ethyl]carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxoethyl]pyrazolo[5,4-c]pyridine-3-carboxamide	1393245: Inhibition of human factor D using CVF-FB as substrate assessed as decrease in formation of factor B cleavage product Ba by ELISA	ic50	0.0300	uM
1-[2-[[2-[(3-chloro-2-fluorophenyl)methylamino]-2-oxoethyl]-cyclopropylamino]-2-oxoethyl]-5-(cyclohexylcarbamoylamino)indazole-3-carboxamide	1918209: Inhibition of human complement factor D using Z-L-Lys-SBzl hydrochloride as substrate preincubated for 15 mins followed by substrate addition and measured by colorimetric method based esterolytic assay	ic50	0.0340	uM
1-[2-[[2-[(3-chloro-2-fluorophenyl)methylamino]-2-oxoethyl]-cyclopropylamino]-2-oxoethyl]-5-[(3,3-difluoropiperidine-1-carbonyl)amino]indazole-3-carboxamide	1918209: Inhibition of human complement factor D using Z-L-Lys-SBzl hydrochloride as substrate preincubated for 15 mins followed by substrate addition and measured by colorimetric method based esterolytic assay	ic50	0.0340	uM
2-[2-[[3-[(3S)-3-amino-2,3-dihydro-1-benzofuran-5-yl]-5-(2-cyanopropan-2-yl)phenyl]methoxy]phenyl]acetic acid	1660713: Inhibition of human complement FD by TR-FRET assay	ic50	0.0400	uM
2-[2-[[3-[(3S)-3-amino-2,3-dihydro-1-benzofuran-5-yl]-5-propan-2-ylphenyl]methoxy]phenyl]acetic acid	1660713: Inhibition of human complement FD by TR-FRET assay	ic50	0.0400	uM
(1R,3S,5R)-3-N-(3-bromophenyl)-2-N-(1-carbamoylindol-3-yl)-2-azabicyclo[3.1.0]hexane-2,3-dicarboxamide	1445601: Inhibition of recombinant human complement factor D catalytic domain using Z-Lys-thiobenzylester as substrate preincubated for 1 hr followed by substrate addition by 2,4-dinitrobenzenesulfonyl-2,7-desmethyl-fluorecein probe based spectrofluorimetric assay	ic50	0.0450	uM
2-[2-[[5-[(3S)-3-amino-2,3-dihydro-1-benzofuran-5-yl]-3,3-dimethyl-2H-1-benzofuran-7-yl]methoxy]phenyl]acetic acid	1660713: Inhibition of human complement FD by TR-FRET assay	ic50	0.0500	uM
(2S,4R)-1-N-(1-carbamoylindol-3-yl)-4-fluoro-2-N-[3-(trifluoromethoxy)phenyl]pyrrolidine-1,2-dicarboxamide	1445601: Inhibition of recombinant human complement factor D catalytic domain using Z-Lys-thiobenzylester as substrate preincubated for 1 hr followed by substrate addition by 2,4-dinitrobenzenesulfonyl-2,7-desmethyl-fluorecein probe based spectrofluorimetric assay	ic50	0.0500	uM
(1R,3S,5R)-2-N-(1-carbamoylindol-3-yl)-3-N-[3-(trifluoromethoxy)phenyl]-2-azabicyclo[3.1.0]hexane-2,3-dicarboxamide	1445601: Inhibition of recombinant human complement factor D catalytic domain using Z-Lys-thiobenzylester as substrate preincubated for 1 hr followed by substrate addition by 2,4-dinitrobenzenesulfonyl-2,7-desmethyl-fluorecein probe based spectrofluorimetric assay	ic50	0.0500	uM
1-[2-[[2-[(3-chloro-2-fluorophenyl)methylamino]-2-oxoethyl]-cyclopropylamino]-2-oxoethyl]-6-hydroxyindazole-3-carboxamide	1918209: Inhibition of human complement factor D using Z-L-Lys-SBzl hydrochloride as substrate preincubated for 15 mins followed by substrate addition and measured by colorimetric method based esterolytic assay	ic50	0.0540	uM
2-[(2R)-2-[3-[(3S)-3-amino-2,3-dihydro-1-benzofuran-5-yl]-5-propan-2-ylphenyl]-3,4-dihydro-2H-1,4-benzoxazin-8-yl]acetic acid	1660713: Inhibition of human complement FD by TR-FRET assay	ic50	0.0600	uM
1-[2-[(1R,3S,5R)-3-[(6-bromo-2-pyridinyl)carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxoethyl]indole-3-carboxamide	1445601: Inhibition of recombinant human complement factor D catalytic domain using Z-Lys-thiobenzylester as substrate preincubated for 1 hr followed by substrate addition by 2,4-dinitrobenzenesulfonyl-2,7-desmethyl-fluorecein probe based spectrofluorimetric assay	ic50	0.0660	uM
1-[2-[(2S)-2-[(6-bromo-2-pyridinyl)carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]indazole-3-carboxamide	1918209: Inhibition of human complement factor D using Z-L-Lys-SBzl hydrochloride as substrate preincubated for 15 mins followed by substrate addition and measured by colorimetric method based esterolytic assay	ic50	0.0670	uM
(2S)-N-(6-bromo-2-pyridinyl)-3-(2-indazol-1-ylacetyl)-1,3-thiazolidine-2-carboxamide	1325992: Inhibition of human serum factor D-mediated complement activation in rabbit erythrocytes assessed as reduction in rabbit erythrocyte hemolysis preincubated with human serum for 15 mins followed by addition of rabbit erythrocytes and Mg-EGTA measured after 30 mins	ic50	0.0770	uM
1-[2-[[2-[(3-chloro-2-fluorophenyl)methylamino]-2-oxoethyl]-cyclopropylamino]-2-oxoethyl]-6-(hydroxymethyl)indazole-3-carboxamide	1918209: Inhibition of human complement factor D using Z-L-Lys-SBzl hydrochloride as substrate preincubated for 15 mins followed by substrate addition and measured by colorimetric method based esterolytic assay	ic50	0.0770	uM
tert-butyl N-[3-carbamoyl-1-[2-[[2-[(3-chloro-2-fluorophenyl)methylamino]-2-oxoethyl]-cyclopropylamino]-2-oxoethyl]indazol-5-yl]carbamate	1918209: Inhibition of human complement factor D using Z-L-Lys-SBzl hydrochloride as substrate preincubated for 15 mins followed by substrate addition and measured by colorimetric method based esterolytic assay	ic50	0.0840	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, affects expression, increases methylation, affects reaction, increases expression	10
Dexamethasone	increases expression, affects cotreatment	4
Particulate Matter	decreases expression, increases abundance	3
bisphenol A	affects cotreatment, increases expression	2
entinostat	increases expression, affects cotreatment	2
Air Pollutants	decreases expression, increases abundance	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
Smoke	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
aristolochic acid I	increases expression	1
TAK-243	increases sumoylation	1
graphene oxide	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
tobacco tar	decreases expression, decreases reaction	1
diallyl disulfide	decreases expression, decreases reaction	1
ferrous chloride	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Resveratrol	affects secretion	1
Temozolomide	increases expression	1
Decitabine	affects expression	1
Arsenic Trioxide	decreases expression	1
Troglitazone	increases expression	1

ChEMBL screening assays

82 unique, capped per target: 81 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2188699	Binding	Inhibition of recombinant human complement factor D after 1 hr	Factor D Inhibitors for the Treatment of AMD: Patent Highlight. — ACS Med Chem Lett
CHEMBL4621383	ADMET	Inhibition of human complement FD by TR-FRET assay	Structure-Based Design and Preclinical Characterization of Selective and Orally Bioavailable Factor XIa Inhibitors: Demonstrating the Power of an Integrated S1 Protease Family Approach. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1VS	Abcam A-549 CFD KO	Cancer cell line	Male

Clinical trials (associated diseases)

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