F11

Summary

F11 (coagulation factor XI, HGNC:3529) is a protein-coding gene on chromosome 4q35.2, encoding Coagulation factor XI (P03951). Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX.

This gene encodes coagulation factor XI of the blood coagulation cascade. This protein is present in plasma as a zymogen, which is a unique plasma coagulation enzyme because it exists as a homodimer consisting of two identical polypeptide chains linked by disulfide bonds. During activation of the plasma factor XI, an internal peptide bond is cleaved by factor XIIa (or XII) in each of the two chains, resulting in activated factor XIa, a serine protease composed of two heavy and two light chains held together by disulfide bonds. This activated plasma factor XI triggers the middle phase of the intrisic pathway of blood coagulation by activating factor IX. Defects in this factor lead to Rosenthal syndrome, a blood coagulation abnormality.

Source: NCBI Gene 2160 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital factor XI deficiency (Definitive, ClinGen)
• Clinical variants (ClinVar): 807 total — 69 pathogenic, 120 likely-pathogenic
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000128

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3529
Approved symbol	F11
Name	coagulation factor XI
Location	4q35.2
Locus type	gene with protein product
Status	Approved
Aliases	FXI
Ensembl gene	ENSG00000088926
Ensembl biotype	protein_coding
OMIM	264900
Entrez	2160

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 26 protein_coding, 2 retained_intron

ENST00000264691, ENST00000403665, ENST00000452239, ENST00000492972, ENST00000503841, ENST00000514715, ENST00000886339, ENST00000886340, ENST00000886341, ENST00000886342, ENST00000886343, ENST00000886344, ENST00000886345, ENST00000886346, ENST00000886347, ENST00000886348, ENST00000886349, ENST00000886350, ENST00000886351, ENST00000886352, ENST00000886353, ENST00000886354, ENST00000886355, ENST00000886356, ENST00000886357, ENST00000886358, ENST00000886359, ENST00000886360

RefSeq mRNA: 2 — MANE Select: NM_000128 NM_000128, NM_001354804

CCDS: CCDS3847, CCDS87285

Canonical transcript exons

ENST00000403665 — 15 exons

Exon	Start	End
ENSE00001198288	186287684	186287823
ENSE00001198294	186286415	186286510
ENSE00001198301	186285638	186285813
ENSE00001198308	186284092	186284260
ENSE00001198316	186280474	186280580
ENSE00001198322	186280223	186280385
ENSE00001198331	186280012	186280121
ENSE00001198342	186276231	186276390
ENSE00001198348	186275787	186275896
ENSE00001198357	186274116	186274275
ENSE00001198366	186273071	186273177
ENSE00001198596	186271609	186271771
ENSE00001198609	186267136	186267191
ENSE00001552233	186266189	186266295
ENSE00003896494	186288453	186289681

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 98.46.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7380 / max 267.5433, expressed in 32 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
50911	0.5949	31
50910	0.1430	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.46	gold quality
liver	UBERON:0002107	97.19	gold quality
body of pancreas	UBERON:0001150	93.47	gold quality
jejunal mucosa	UBERON:0000399	90.16	gold quality
renal medulla	UBERON:0000362	88.18	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.31	gold quality
pancreas	UBERON:0001264	86.65	gold quality
epithelial cell of pancreas	CL:0000083	84.98	gold quality
duodenum	UBERON:0002114	84.30	gold quality
pancreatic ductal cell	CL:0002079	82.84	silver quality
adult mammalian kidney	UBERON:0000082	82.16	gold quality
gall bladder	UBERON:0002110	81.73	gold quality
buccal mucosa cell	CL:0002336	81.29	silver quality
kidney	UBERON:0002113	78.81	gold quality
metanephros cortex	UBERON:0010533	77.07	gold quality
islet of Langerhans	UBERON:0000006	75.27	gold quality
cortex of kidney	UBERON:0001225	72.70	gold quality
nephron tubule	UBERON:0001231	72.67	gold quality
kidney epithelium	UBERON:0004819	71.81	silver quality
jejunum	UBERON:0002115	71.41	gold quality
type B pancreatic cell	CL:0000169	70.42	gold quality
endometrium epithelium	UBERON:0004811	67.22	gold quality
renal glomerulus	UBERON:0000074	66.94	silver quality
metanephric glomerulus	UBERON:0004736	66.84	silver quality
metanephros	UBERON:0000081	66.36	gold quality
parotid gland	UBERON:0001831	66.12	gold quality
right lung	UBERON:0002167	66.10	gold quality
upper lobe of left lung	UBERON:0008952	65.86	gold quality
upper lobe of lung	UBERON:0008948	65.46	gold quality
frontal pole	UBERON:0002795	64.74	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting F11, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-7151-5P	99.37	67.82	613
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-20B-3P	99.29	67.05	784
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-4520-2-3P	99.14	69.28	1009
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-371A-5P	99.08	66.51	1914
HSA-MIR-5001-3P	98.91	67.28	1394
HSA-MIR-487A-5P	98.85	69.37	993
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-219A-2-3P	98.62	68.78	797
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-7850-5P	98.12	67.28	1111
HSA-MIR-124-5P	98.11	67.65	1095

Literature-anchored findings (GeneRIF, showing 40)

• HK binding to FXI involves multiple apple domains, with F2 being most important. The findings demonstrate a similarity in mechanism for FXI and prekallikrein binding to HK (PMID:11733491)
• role of HNF-4alpha in hepatocyte-specific expression (PMID:11891231)
• interaction of coagulation factor XI with human umbilical vein endothelial cells (HUVEC) and with platelets (PMID:12029092)
• Data show that the rate of factor IX activation by factor XIa is not enhanced by biological surfaces, and activated platelet surfaces are thrombogenic while endothelial surfaces are not. (PMID:12167623)
• plasma kallikrein and FXIa activate pro-HGF in vitro (PMID:12372819)
• role of factor IX gamma-carboxyglutamic acid domain in interactions between factor IX and factor XIa (PMID:12496253)
• factor XI is localized to GPIb in membrane rafts and that this association is important for promoting the activation of factor XI by thrombin on the platelet surface (PMID:12517745)
• The frequency distributions of platelet polymorphisms and of prothrombotic polymorphisms were not different between patients with severe FXI deficiency who experienced or not an AMI. (PMID:12871398)
• prekallikrein abolished Factor XI or -Factor XIa binding to vascular endothelial cell suspensions (PMID:12944405)
• FXI has no effect on thrombin generation at 10 pm TF and physiological concentrations of Vitamin K-Dependent Proteins (VKDP); platelets and plasma FXI are able to compensate for the inhibitory effects of elevated VKDP (PMID:14521591)
• high levels of coagulation FXI, FIX and FVIII are related to risk of inherited thrombophilia syndrome (PMID:14521595)
• The data indicate that FXI domains A2 and A3 make contributions to dimer formation and stabilize this dimeric conformation (PMID:14629467)
• new ancient mutation in exon 4 resulting in Q88X, specific to patients from Nantes, France (PMID:14717969)
• Platelet-localized feedback activation of factor XI by thrombin plays an important role in maintaining normal hemostasis as well as in sustaining thrombus formation when the TF pathway is inhibited by tissue factor pathway inhibitor. (PMID:15072993)
• Data describe the structural role of glycine(193) in the serine protease, factor XIa. (PMID:15090552)
• The FXI gene mutations Trp228stop, Glu323Lys and Leu172Pro attribute to the pathogenesis of the factor XI deficiency in Chinese. (PMID:15182578)
• whole gene deletion as the causative mutation of factor XI deficiency, the result of unequal homologous recombination between flanking Alu repeat sequences (PMID:15226185)
• binding of FXI to GPIbalpha is mediated by amino acids in the A3 domain in the presence or absence of HK. (PMID:15317813)
• FXI binds to glycoprotein Ibalpha at sites comprising the leucine-rich repeat sequences within the NH2-terminal globular domain that are separate and distinct from the thrombin-binding site (PMID:15375170)
• nature of possible platelet-associated FXI activity (PMID:15456479)
• the platelets of both normal and FXI deficient individuals contain FXI mRNA that is identical to the mRNA found in liver; the FXI message is not alternatively spliced in platelets (PMID:15456480)
• Glu555 alters the electrostatic charge around the active site, and would sterically interfere with the interaction between the FXIa site and residues on F9 and antithrombin. FXI-Glu555 is the first reported FXI variant with a defect in FIX activation. (PMID:15456490)
• Crystal structures of the FXIa catalytic domain complexed to ecotin mutants (PMID:15545266)
• structural characterization of FXI disease-causing mutations to complement phenotypic ata (PMID:15634276)
• analysis of missense mutations in two patients with factor XI deficiency (Val271Leu and Tyr351Ser) and one patient with combined factor XI and factor IX deficiency (Phe349Val)[letter] (PMID:15842381)
• To provide a complete database of mutations and polymorphisms associated with factor XI deficiency, all available data on hereditary factor XI deficiency from main biological and medical databases were collected (PMID:15870541)
• For optimal rates of factor IX activation in solution or on the physiologically relevant surface of activated platelets, a preformed dimer of factor XI is not required. (PMID:16042419)
• Six novel missense mutations were identified in factor XI deficiency. (PMID:16079124)
• Arg15, Phe34, Pro13, and Arg20 are important for FXIa inhibition by PN2 Kunitz protease inhibitor domain (PMID:16085935)
• crystallographic analysis of Factor XI with mutated surface residues bound to benzamidine (PMID:16204896)
• In 3 cases, the Glu117stop mutation caused a quantitative deficiency of factor XI by reducing mRNA levels. (PMID:16330457)
• 31 novel mutations in the F11 gene are associated with Factor XI deficiency. (PMID:16835901)
• The results demonstrate that basic amino acids in the autolysis loop of fXIa are important determinants of serpin specificity. (PMID:16878977)
• coagulation factor XI (FXIP520L) has a proline to leucine substitution at residue 520, which results in a catalytic defect (PMID:17229051)
• the F283L mutation leads to increased dimer dissociation by stabilizing a monomeric state with altered side-chain packing that is unfavorable for homodimer formation (PMID:17257616)
• Report five missense mutations of Factor XI as being causative of factor XI deficiency. (PMID:17549289)
• a novel mutation, a C-to-G transition at position 1394 in exon 12 in the FXI gene (F11 c.1394 C>G). This transition resulted in a missense mutation (Gln433Glu), which led to the disruption of the catalytic domain structure of the FXI molecule. (PMID:17581330)
• review of the role of FXI in thrombosis and hemostasis, and the etiology and antithrombotic effect of FXI deficiency (PMID:17597996)
• activation of FXI by thrombin in solution or on the surface of activated platelets does not appear to play a significant role in a plasma environment (PMID:17652512)
• ADAMTS13/FXI complexes are insignificant in plasma (PMID:17768109)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	F11	ENSMUSG00000031645
rattus_norvegicus	F11	ENSRNOG00000013684

Paralogs (16): F7 (ENSG00000057593), F9 (ENSG00000101981), HGFAC (ENSG00000109758), F10 (ENSG00000126218), KLK10 (ENSG00000129451), F12 (ENSG00000131187), C1RL (ENSG00000139178), C1R (ENSG00000159403), KLKB1 (ENSG00000164344), C1S (ENSG00000182326), PRSS55 (ENSG00000184647), CFD (ENSG00000197766), CFI (ENSG00000205403), PRSS51 (ENSG00000253649), HP (ENSG00000257017), HPR (ENSG00000261701)

Protein

Protein identifiers

Coagulation factor XI — P03951 (reviewed: P03951)

Alternative names: Plasma thromboplastin antecedent

All UniProt accessions (4): P03951, D6RB32, H0Y596, X6R3B1

UniProt curated annotations — full annotation on UniProt →

Function. Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX.

Subunit / interactions. Homodimer; disulfide-linked. Can form non-covalently bonded homodimers. After activation the heavy and light chains are also linked by a disulfide bond. Interacts (activated) with F9 (inactive and activated) in calcium-dependent manner. Forms a heterodimer with SERPINA5. Interacts with Anopheles gambiae D7L2. Interacts (activated) with guianensin, an anticoagulant protein from Simulium guianense saliva.

Subcellular location. Secreted.

Tissue specificity. Isoform 2 is produced by platelets and megakaryocytes but absent from other blood cells.

Post-translational modifications. N-glycosylated on both chains. N-glycosylated sites mainly consist of nonfucosylated sialylated biantennary (in high abundance) and/or triantennary (in low abundance) complex structures. Glycosylation at Asn-163 uses a rare non-canonical Asn-X-Cys glycosite. Activated by factor XIIa (or XII), which cleaves each polypeptide after Arg-387 into the light chain, which contains the active site, and the heavy chain, which associates with high molecular weight (HMW) kininogen. Activated by F12 (activated); the presence of negatively charged surfaces accelerates activation. Activated by F2 (thrombin); the presence of negatively charged surfaces, such as polyphosphate and dextran sulfate, strongly accelerates activation. Autoactivated; the presence of negatively charged surfaces, such as polyphosphate and dextran sulfate, accelerates autoactivation and autolysis.

Disease relevance. Factor XI deficiency (FA11D) [MIM:612416] A hemorrhagic disease characterized by reduced levels and activity of factor XI resulting in moderate bleeding symptoms, usually occurring after trauma or surgery. Patients usually do not present spontaneous bleeding but women can present with menorrhagia. Hemorrhages are usually moderate. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by SERPINA5.

Similarity. Belongs to the peptidase S1 family. Plasma kallikrein subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P03951-1	1	yes
P03951-2	2, Platelet

RefSeq proteins (2): NP_000119, NP_001341733 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000177	Apple	Domain
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR003609	Pan_app	Domain
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR043504

Pfam: PF00024, PF00089

Enzyme classification (BRENDA):

• EC 3.4.21.27 — coagulation factor XIa (BRENDA: 9 organisms, 83 substrates, 287 inhibitors, 63 Km, 52 kcat entries)

Substrate kinetics (BRENDA)

18 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-PYROGLU-L-PRO-L-ARG-4-NITROANILIDE	0.205–0.852	13
L-PYROGLUTAMYL-L-PROLYL-L-ARGININYL-P-NITROANILI	0.552–0.993	9
FACTOR IX	0.0001–0.151	7
L-GLU-L-GLU-L-PRO-L-ARG-4-NITROANILIDE	0.28–0.41	6
L-GLU-PRO-ARG-4-NITROANILIDE	0.0455–0.1283	4
S-2366	0.225–0.384	4
L-PYROGLUTAMYL-L-PRO-L-ARG-4-NITROANILIDE	0.45–0.59	3
L-PYROGLUTAMYL-L-PROLYL-L-ARGINYL-P-NITROANILIDE	0.4–352	3
PYROGLU-PRO-ARG-4-NITROANILIDE	0.26–0.4	2
BENZYLOXYCARBONYL-GLY-PRO-4-NITROANILIDE	0.09	1
D-ILE-PRO-ARG-4-NITROANILIDE	0.34	1
FACTOR FIX	0.09	1
FACTOR IX 10-MER	0.3	1
FACTOR IX MUTANT G317E	0.0004	1
FACTOR IX MUTANT G317R	0.0003	1

UniProt features (176 total): sequence variant 63, strand 45, helix 21, disulfide bond 19, glycosylation site 5, turn 5, domain 5, mutagenesis site 4, active site 3, chain 2, signal peptide 1, sequence conflict 1, binding site 1, splice variant 1

Structure

Experimental structures (PDB)

114 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7MBO	X-RAY DIFFRACTION	0.92
6TS4	X-RAY DIFFRACTION	1.17
4CRG	X-RAY DIFFRACTION	1.25
8BO6	X-RAY DIFFRACTION	1.25
8BO7	X-RAY DIFFRACTION	1.25
6USY	X-RAY DIFFRACTION	1.26
6TS5	X-RAY DIFFRACTION	1.29
6TS6	X-RAY DIFFRACTION	1.33
7V11	X-RAY DIFFRACTION	1.47
5EXN	X-RAY DIFFRACTION	1.49
7V16	X-RAY DIFFRACTION	1.5
7V17	X-RAY DIFFRACTION	1.52
5TKS	X-RAY DIFFRACTION	1.55
7V13	X-RAY DIFFRACTION	1.59
3BG8	X-RAY DIFFRACTION	1.6
4CRC	X-RAY DIFFRACTION	1.6
6VLU	X-RAY DIFFRACTION	1.6
4D7F	X-RAY DIFFRACTION	1.62
7V12	X-RAY DIFFRACTION	1.63
7V15	X-RAY DIFFRACTION	1.68
7V14	X-RAY DIFFRACTION	1.7
4CR9	X-RAY DIFFRACTION	1.7
8BO5	X-RAY DIFFRACTION	1.7
6VLV	X-RAY DIFFRACTION	1.72
1ZHR	X-RAY DIFFRACTION	1.73
4CRE	X-RAY DIFFRACTION	1.73
7V18	X-RAY DIFFRACTION	1.73
8BO4	X-RAY DIFFRACTION	1.75
4D76	X-RAY DIFFRACTION	1.77
7V10	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P03951-F1	86.94	0.65

Antibody-complex structures (SAbDab): 3 — 6AOD, 6HHC, 6R8X

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 (3): 575 (charge relay system); 431 (charge relay system); 480 (charge relay system)

Ligand- & substrate-binding residues (1): 547–550

Disulfide bonds (19): 20–103, 29, 46–76, 50–56, 110–193, 136–165, 140–146, 200–283, 226–255, 230–236, 291–374, 317–346, 321–327, 339, 380–500, 416–432, 514–581, 545–560, 571–599

Glycosylation sites (5): 90, 126, 163, 450, 491

Mutagenesis-validated functional residues (4):

Position	Phenotype
302	reduces dimerization. abolishes dimerization; when associated with a-308.
308	reduces dimerization. abolishes dimerization; when associated with a-302.
344	abolishes dimerization.
347	reduces dimerization.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-9673221	Defective F9 activation
R-HSA-9769739	Regulation of clotting cascade
R-HSA-9769743	Amplification and propagation of coagulation cascade
R-HSA-9935598	FXIIa, PKa-dependent activation of coagulation pathway
R-HSA-140837

MSigDB gene sets: 123 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GOBP_PROTEIN_ACTIVATION_CASCADE, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_REGULATION_OF_COAGULATION, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_NEGATIVE_REGULATION_OF_COAGULATION, GOBP_WOUND_HEALING, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_PROTEIN_MATURATION, GOBP_REGULATION_OF_FIBRINOLYSIS, HOSHIDA_LIVER_CANCER_SUBCLASS_S3, MODULE_109, GOBP_REGULATION_OF_RESPONSE_TO_WOUNDING, HSIAO_LIVER_SPECIFIC_GENES

GO Biological Process (6): blood coagulation (GO:0007596), plasminogen activation (GO:0031639), positive regulation of fibrinolysis (GO:0051919), proteolysis (GO:0006508), hemostasis (GO:0007599), regulation of blood coagulation (GO:0030193)

GO Molecular Function (8): serine-type endopeptidase activity (GO:0004252), heparin binding (GO:0008201), serine-type peptidase activity (GO:0008236), identical protein binding (GO:0042802), serine-type aminopeptidase activity (GO:0070009), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (5): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), membrane (GO:0016020), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Coagulation pathway	2
Defective factor IX causes hemophilia B	1
Regulation of clotting cascade	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
hemostasis	1
wound healing	1
coagulation	1
zymogen activation	1
negative regulation of blood coagulation	1
fibrinolysis	1
positive regulation of biological process	1
regulation of fibrinolysis	1
protein metabolic process	1
regulation of body fluid levels	1
blood coagulation	1
regulation of response to external stimulus	1
regulation of coagulation	1
regulation of wound healing	1
regulation of hemostasis	1
endopeptidase activity	1
serine-type peptidase activity	1
glycosaminoglycan binding	1
sulfur compound binding	1
peptidase activity	1
serine hydrolase activity	1
protein binding	1
aminopeptidase activity	1
serine-type exopeptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
membrane	1
cell periphery	1
extracellular vesicle	1

Protein interactions and networks

STRING

978 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
F11	KNG1	P01042	995
F11	F8	P00451	925
F11	F3	P13726	840
F11	SERPING1	P05155	758
F11	GP1BA	P07359	757
F11	VWF	P04275	706
F11	TFPI	P10646	657
F11	CPB2	Q96IY4	653
F11	SERPINC1	P01008	623
F11	LRP8	Q14114	581
F11	SERPINF2	P08697	572
F11	A2M	P01023	555
F11	F9	P00740	550
F11	KLK4	Q9Y5K2	535
F11	THBD	P07204	532

IntAct

15 interactions, top by confidence:

A	B	Type	Score
PRCC	BCAS2	psi-mi:“MI:0914”(association)	0.530
eco	F11	psi-mi:“MI:0407”(direct interaction)	0.440
F11	eco	psi-mi:“MI:0407”(direct interaction)	0.440
F11	VDAC1	psi-mi:“MI:0915”(physical association)	0.400
F11	KRT8	psi-mi:“MI:0915”(physical association)	0.400
	CD5L	psi-mi:“MI:0915”(physical association)	0.400
	LECT2	psi-mi:“MI:0915”(physical association)	0.400
SPG11	F11	psi-mi:“MI:0915”(physical association)	0.370
F11	APP	psi-mi:“MI:0914”(association)	0.350
BRME1	F11	psi-mi:“MI:0914”(association)	0.350

BioGRID (12): F11 (Affinity Capture-MS), APP (Affinity Capture-MS), CRELD2 (Affinity Capture-MS), N4BP2L2 (Affinity Capture-MS), F11 (Reconstituted Complex), KRT8 (Proximity Label-MS), VDAC1 (Proximity Label-MS), F11 (Reconstituted Complex), F11 (Affinity Capture-MS), CRELD2 (Affinity Capture-MS), APP (Affinity Capture-MS), F11 (Affinity Capture-MS)

ESM2 similar proteins: A6MFK7, A6MFK8, B5G6G5, P00741, P00750, P03951, P03952, P11214, P14210, P14272, P15638, P17945, P19637, P26262, P33587, P81428, P82807, P83370, P86091, P98119, P98121, Q05589, Q08048, Q1L658, Q28198, Q2KJ63, Q56VR3, Q58L93, Q58L94, Q58L95, Q58L96, Q5NTB3, Q5RDI1, Q5RF29, Q66TN7, Q6DIV5, Q6IE14, Q6SA95, Q6UXH9, Q6ZWK6

Diamond homologs: A0A126GUP6, A0A182C2Z2, A0A1S4H5M5, A8JUP7, B5U2W0, B7YZU2, F5HKX0, O15393, O35453, O60235, O60259, O97366, P00774, P03951, P03952, P05049, P05981, P08419, P09871, P10323, P13582, P14272, P21902, P23578, P25155, P26262, P28175, P29293, P31394, P33587, P35035, P35036, P35037, P35039, P35041, P35045, P35046, P35047, P40313, P48038

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
F11	“up-regulates activity”	“GPIb-IX-V complex”	binding
F12	“up-regulates activity”	F11	cleavage
F11	“up-regulates activity”	F9	cleavage
F11	“up-regulates activity”	HGF	cleavage
SERPINC1	“down-regulates activity”	F11	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	69
Likely pathogenic	120
Uncertain significance	220
Likely benign	238
Benign	51

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069881	NM_000128.4(F11):c.1465del (p.Thr489fs)	Pathogenic
1073465	NM_000128.4(F11):c.325+1G>A	Pathogenic
11891	NM_000128.4(F11):c.403G>T (p.Glu135Ter)	Pathogenic
11892	NM_000128.4(F11):c.901T>C (p.Phe301Leu)	Pathogenic
11893	NM_000128.4(F11):c.1029-2A>G	Pathogenic
11894	NM_000128.4(F11):c.485+5G>C	Pathogenic
11895	NM_000128.4(F11):c.1378T>G (p.Phe460Val)	Pathogenic
11904	NM_000128.4(F11):c.1760G>C (p.Trp587Ser)	Pathogenic
11905	NC_000004.12:g.(186261554_186262508)_(?_186293752)del	Pathogenic
1333004	Single allele	Pathogenic
1367768	NM_000128.4(F11):c.1006C>T (p.Gln336Ter)	Pathogenic
1388644	NM_000128.4(F11):c.1235_1236insAA (p.His414fs)	Pathogenic
1444159	NM_000128.4(F11):c.1443del (p.Ile481fs)	Pathogenic
1457590	NM_000128.4(F11):c.738G>A (p.Trp246Ter)	Pathogenic
1459564	NM_000128.4(F11):c.1746del (p.Lys582fs)	Pathogenic
188757	NM_000128.4(F11):c.961_962del (p.Cys321fs)	Pathogenic
188810	NM_000128.4(F11):c.325G>A (p.Ala109Thr)	Pathogenic
188887	NM_000128.4(F11):c.1556G>A (p.Trp519Ter)	Pathogenic
188914	NM_000128.4(F11):c.408C>A (p.Cys136Ter)	Pathogenic
189094	NM_000128.4(F11):c.730C>T (p.Gln244Ter)	Pathogenic
189115	NM_000128.4(F11):c.1107C>A (p.Tyr369Ter)	Pathogenic
189129	NM_000128.4(F11):c.908del (p.Gly303fs)	Pathogenic
2055640	NM_000128.4(F11):c.760_761insAGATG (p.Leu254fs)	Pathogenic
2170262	NM_000128.4(F11):c.1726G>T (p.Gly576Ter)	Pathogenic
2188764	NM_000128.4(F11):c.55+1del	Pathogenic
2422395	NC_000004.11:g.(?187208828)(187208988_?)del	Pathogenic
2422397	NC_000004.11:g.(?187186995)(187188355_?)del	Pathogenic
2422398	NC_000004.11:g.(?187201156)(187201744_?)del	Pathogenic
2580632	NM_000128.4(F11):c.727dup (p.Ser243fs)	Pathogenic
2715165	NM_000128.4(F11):c.-1-4_11del	Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

4116 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:186284157:T:A	W401R	0.991
4:186284157:T:C	W401R	0.991
4:186286491:G:C	W519C	0.991
4:186286491:G:T	W519C	0.991
4:186288516:A:C	S594R	0.991
4:186288518:C:A	S594R	0.991
4:186288518:C:G	S594R	0.991
4:186284159:G:C	W401C	0.989
4:186284159:G:T	W401C	0.989
4:186284151:T:A	W399R	0.988
4:186284151:T:C	W399R	0.988
4:186286489:T:A	W519R	0.988
4:186286489:T:C	W519R	0.988
4:186288587:G:C	W617C	0.987
4:186288587:G:T	W617C	0.987
4:186285777:G:C	A482P	0.986
4:186288521:G:C	W595C	0.985
4:186288521:G:T	W595C	0.985
4:186287740:T:A	C545S	0.984
4:186287741:G:C	C545S	0.984
4:186287785:T:A	C560S	0.984
4:186287786:G:C	C560S	0.984
4:186287818:T:A	C571S	0.983
4:186287819:G:C	C571S	0.983
4:186271719:T:C	C56R	0.981
4:186271728:T:C	F59L	0.981
4:186271730:C:A	F59L	0.981
4:186271730:C:G	F59L	0.981
4:186280019:T:A	C255S	0.981
4:186280020:G:C	C255S	0.981

dbSNP variants (sampled 300 via entrez): RS10002206 (4:186287501 T>C,G), RS1000225845 (4:186276105 TA>T,TAA), RS1000442536 (4:186270423 G>A,C), RS1000752736 (4:186278718 A>G), RS1000790610 (4:186270236 T>C), RS1000791038 (4:186290058 A>G), RS1000938598 (4:186278369 C>A,G), RS1000973782 (4:186288398 G>C), RS1001000497 (4:186272827 A>G), RS1001503825 (4:186267598 T>C), RS1001724435 (4:186267312 T>G), RS1001843707 (4:186266042 T>A,C), RS1001945970 (4:186275255 C>T), RS1002061387 (4:186265813 A>G), RS1002203014 (4:186277318 C>G)

Disease associations

OMIM: gene MIM:264900 | disease phenotypes: MIM:612416, MIM:227600

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital factor XI deficiency	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
congenital factor XI deficiency	Definitive	SD

Mondo (4): congenital factor XI deficiency (MONDO:0012897), thrombocytopenia (MONDO:0002049), factor XI deficiency (MONDO:0020587), congenital factor X deficiency (MONDO:0009212)

Orphanet (2): Congenital factor XI deficiency (Orphanet:329), Congenital factor X deficiency (Orphanet:328)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D005173	Factor XI Deficiency	C15.378.100.100.325; C15.378.100.141.325; C15.378.463.325; C16.320.099.325
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2820 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 5,622 (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
CHEMBL266349	MELAGATRAN	4	5,421
CHEMBL4112929	MILVEXIAN	3	134
CHEMBL5314583	FRUNEXIAN	2	21
CHEMBL4073292	BMS-962212	1	29
CHEMBL5415591	ONO-7684	1	17

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2289252	Toxicity	3	hormonal contraceptives for systemic use

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3756009	F11		0.00	0
rs2289252	F11	3	3.00	1	hormonal contraceptives for systemic use

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Blood coagulation components

Most potent curated ligand interactions (6 total), top 6:

Ligand	Action	Affinity	Parameter
abelacimab	Inhibition	11.33	pKd
milvexian	Inhibition	9.96	pKi
FXIa inhibitor 3f	Inhibition	9.77	pKi
osocimab	Inhibition	8.62	pKd
EP-7041	Inhibition	8.15	pIC50
alpha-ketothiazole analogue 36	Inhibition	7.5	pIC50

Binding affinities (BindingDB)

1979 measured of 2576 human assays (2580 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
methyl N-[(10R,14S)-14-[4-(3-chloro-6-cyano-2-fluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.03 nM	US-9951071: Dihydropyridone P1 as factor XIa inhibitors
methyl N-[(10R,14S)-14-[4-[3-chloro-6-(difluoromethoxy)-2-fluorophenyl]-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,18-diazatricyclo[13.3.1.02,7]nonadeca-1(18),2(7),3,5,15(19),16-hexaen-5-yl]carbamate	KI	0.04 nM	US-9951071: Dihydropyridone P1 as factor XIa inhibitors
methyl N-[(12R,14R)-14-[5-(3-chloro-2,6-difluorophenyl)-1-oxidopyridin-1-ium-2-yl]-12,17-dimethyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.04 nM	US-10214512
(10R,14S)-14-[4-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2,4,6,15,17-hexaen-9-one	KI	0.05 nM	US-9951071: Dihydropyridone P1 as factor XIa inhibitors
methyl N-[(10R,14S)-17-chloro-14-[4-(3-chloro-2,6-difluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.05 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
methyl N-[(10R,14S)-14-[4-[3-chloro-6-(difluoromethoxy)-2-fluorophenyl]-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.06 nM	US-9951071: Dihydropyridone P1 as factor XIa inhibitors
(13R,17S)-17-[4-(3-chloro-2,6-difluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-6,13-dimethyl-12-oxo-7,11,19-triazatetracyclo[16.3.1.02,10.04,8]docosa-1(22),2(10),3,5,8,18,20-heptaene-5-carboxylic acid	KI	0.06 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
(10R,14S)-14-[4-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]-6-oxo-2,3-dihydropyridin-1-yl]-4,5-difluoro-10-methyl-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2,4,6,15,17-hexaen-9-one	KI	0.07 nM	US-9951071: Dihydropyridone P1 as factor XIa inhibitors
4-[(2-{5-[5-chloro-2-(1H- tetrazol-1-yl)phenyl]-1- oxidopyridin-2-yl}-3- cyclopropylpropanoyl) amino]-2-fluorobenzoic acid	IC50	0.07 nM	US-9783530: Factor Xla inhibitors
2-[(2-methylpropan-2-yl)oxy]ethyl N-[(10R,14S)-14-[4-(3-chloro-2,6-difluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.08 nM	US-9951071: Dihydropyridone P1 as factor XIa inhibitors
2-hydroxyethyl N-[(10R,14S)-14-[4-(3-chloro-2,6-difluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.08 nM	US-9951071: Dihydropyridone P1 as factor XIa inhibitors
methyl N-[(14R)-14-[5-[5-fluoro-2-(tetrazol-1-yl)phenyl]-1-oxidopyridin-1-ium-2-yl]-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15-pentaen-5-yl]carbamate	KI	0.08 nM	US-10214512
methyl N-[(10R,14S)-14-[4-(3-chloro-6-cyano-2-fluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-17-methoxy-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.09 nM	US-9951071: Dihydropyridone P1 as factor XIa inhibitors
methyl N-[(10R,14S)-14-[4-[5-chloro-2-(trifluoromethyl)phenyl]-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.09 nM	US-9951071: Dihydropyridone P1 as factor XIa inhibitors
(10S,14S)-14-[4-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]-6-oxo-2,3-dihydropyridin-1-yl]-10-propan-2-yl-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2,4,6,15,17-hexaen-9-one	KI	0.09 nM	US-9951071: Dihydropyridone P1 as factor XIa inhibitors
methyl N-[(10R,14S)-14-[4-(6-cyano-2-fluoro-3-methylphenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.09 nM	US-9951071: Dihydropyridone P1 as factor XIa inhibitors
(S) 5-(5-chloro-2-(1H-tetrazol-1-yl)phenyl)-2-(25-fluoro-4-oxo-3-aza-1(1,3),2(1,2)-dibenzenacyclononaphane-9-yl)pyridine 1-oxide	KI	0.09 nM	US-10214512
methyl N-[(12R,14R)-14-[5-[2-(difluoromethoxy)-6-fluorophenyl]-1-oxidopyridin-1-ium-2-yl]-12,17-dimethyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.09 nM	US-10214512
methyl N-[(10R,14S)-14-[4-[3-chloro-2-fluoro-6-(trifluoromethyl)phenyl]-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.1 nM	US-9951071: Dihydropyridone P1 as factor XIa inhibitors
methyl N-[(10R,14S)-14-[4-(3-chloro-6-ethynyl-2-fluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.1 nM	US-9951071: Dihydropyridone P1 as factor XIa inhibitors
(9R,13S)-13-[4-[5-chloro-2-(4-chlorotriazol-1-yl)phenyl]-6-oxo-1,3-diazinan-1-yl]-3-(difluoromethyl)-9-methyl-3,4,7,15-tetrazatricyclo[12.3.1.02,6]octadeca-1(18),2(6),4,14,16-pentaen-8-one	KI	0.1 nM	US-9453018: Pyrimidinones as factor XIa inhibitors
(9R,13S)-13-[4-[5-chloro-2-[4-(trifluoromethyl)triazol-1-yl]phenyl]-6-oxo-1,3-diazinan-1-yl]-3,9-dimethyl-3,4,7,15-tetrazatricyclo[12.3.1.02,6]octadeca-1(18),2(6),4,14,16-pentaen-8-one	KI	0.1 nM	US-9453018: Pyrimidinones as factor XIa inhibitors
(9R,13S)-13-[4-[5-chloro-2-[4-(trifluoromethyl)triazol-1-yl]phenyl]-6-oxo-1,3-diazinan-1-yl]-3-(difluoromethyl)-9-methyl-3,4,7,15-tetrazatricyclo[12.3.1.02,6]octadeca-1(18),2(6),4,14,16-pentaen-8-one	KI	0.1 nM	US-9453018: Pyrimidinones as factor XIa inhibitors
(9R,13S)-13-[4-[5-chloro-2-[4-(trifluoromethyl)triazol-1-yl]phenyl]-6-oxo-1,3-diazinan-1-yl]-3,9-dimethyl-3,4,7,17-tetrazatricyclo[12.3.1.02,6]octadeca-1(17),2(6),4,14(18),15-pentaen-8-one	KI	0.1 nM	US-9453018: Pyrimidinones as factor XIa inhibitors
BDBM304229	IC50	0.1 nM	US-10143681: Factor XIa inhibitors
5-(5-Chloro-2-(1H-tetrazol-1-yl)phenyl)-2-(24-((methoxycarbonyl)amino)-4-oxo-3-aza-1(1,3),2(1,2) -dibenzenacyclononaphane-9-yl)pyridine 1-oxide	KI	0.1 nM	US-10214512
methyl N-[(10R,14R)-14-[5-(2,6-difluorophenyl)-1-oxidopyridin-1-ium-2-yl]-10,17-dimethyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.1 nM	US-10214512
methyl N-[(10R,14S)-14-[4-[3-chloro-2-fluoro-6-(2H-triazol-4-yl)phenyl]-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.11 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
methyl N-[(14S)-14-[5-[5-chloro-2-(4-cyclopropyltriazol-1-yl)phenyl]-1-oxidopyridin-1-ium-2-yl]-9-oxo-8-azatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.11 nM	US-10214512
methyl N-[(14R)-14-[5-[2-fluoro-6-(trifluoromethyl)phenyl]-1-oxidopyridin-1-ium-2-yl]-17-methyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.11 nM	US-10214512
methyl N-[(14R)-14-[5-[2-(difluoromethoxy)-5-fluorophenyl]-1-oxidopyridin-1-ium-2-yl]-17-methyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.12 nM	US-10214512
methyl N-[(10R,14S)-14-[4-[5-chloro-2-(difluoromethoxy)phenyl]-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.13 nM	US-9951071: Dihydropyridone P1 as factor XIa inhibitors
2-(25-carboxy-4-oxo-3-aza-1(1,3),2(1,2)-dibenzenacyclononaphane-9-yl)-5-(3-chloro-2-fluoro-6-(1H-tetrazol-1-yl)phenyl)pyridine 1-oxide	KI	0.13 nM	US-10214512
methyl N-[(14S)-14-[5-[5-chloro-2-(4-chlorotriazol-1-yl)phenyl]-1-oxidopyridin-1-ium-2-yl]-9-oxo-8-azatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.13 nM	US-10214512
methyl N-[14-[5-(3-chloro-2,6-difluorophenyl)-1-oxidopyridin-1-ium-2-yl]-17-ethyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.13 nM	US-10214512
methyl N-[(10R,14R)-14-[5-[6-(difluoromethoxy)-2,3-difluorophenyl]-1-oxidopyridin-1-ium-2-yl]-10,17-dimethyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.13 nM	US-10214512
(R)-trans-4-{[2-{5-[3-chloro-6-(difluoromethoxy)-2-fluorophenyl]-1-oxidopyridin-2-yl}-3-(4-hydroxycyclohexyl)propanoyl]amino}benzoic Acid	IC50	0.14 nM	US-10143681: Factor XIa inhibitors
4-{[(2R)-2-{5-[5-chloro-2- (1H-tetrazol-1-yl)phenyl]- 1-oxidopyridin-2-yl}-3- cyclopropylpropanoyl] amino}benzoic acid	IC50	0.14 nM	US-9783530: Factor Xla inhibitors
9-(5-(5-chloro-2-(1h-tetrazol-1-yl)phenyl)-1-oxidopyridin-2-yl)-15-fluoro-24-((methoxycarbonyl)amino)-4-oxo-3-aza-1(2,4)-pyridin-1-iuma -2(1,2)-benzenacyclononaphane 11-oxide	KI	0.14 nM	US-10214512
methyl N-[14-[5-[5-chloro-2-(difluoromethoxy)phenyl]-1-oxidopyridin-1-ium-2-yl]-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15-pentaen-5-yl]carbamate	KI	0.14 nM	US-10214512
methyl N-[(14R)-14-[5-[2-(difluoromethoxy)-6-fluorophenyl]-1-oxidopyridin-1-ium-2-yl]-17-methyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.14 nM	US-10214512
(14R)-5-amino-14-[5-(3-chloro-2,6-difluorophenyl)-1-oxidopyridin-1-ium-2-yl]-17-methyl-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-9-one	KI	0.14 nM	US-10214512
methyl N-[(10R,14R)-17-cyclopropyl-14-[5-(2,6-difluorophenyl)-1-oxidopyridin-1-ium-2-yl]-10-methyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.14 nM	US-10214512
methyl N-[(10R,14R)-14-[5-[2-(difluoromethoxy)-6-fluorophenyl]-1-oxidopyridin-1-ium-2-yl]-17-ethyl-10-methyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.14 nM	US-10214512
(9R,13S)-13-[5-[5-chloro-2-(4-chlorotriazol-1-yl)phenyl]-1-oxidopyridin-1-ium-2-yl]-3-(difluoromethyl)-9-methyl-3,4,7-triazatricyclo[12.3.1.02,6]octadeca-1(18),2(6),4,14,16-pentaen-8-one	KI	0.14 nM	US-10214512
methyl N-[(10R,14S)-14-[4-(3-chloro-6-cyano-2-fluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,18-diazatricyclo[13.3.1.02,7]nonadeca-1(18),2(7),3,5,15(19),16-hexaen-5-yl]carbamate	KI	0.15 nM	US-9951071: Dihydropyridone P1 as factor XIa inhibitors
methyl N-[(14R)-14-[5-[2-(difluoromethoxy)-6-fluorophenyl]-1-oxidopyridin-1-ium-2-yl]-17-ethyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.15 nM	US-10214512
methyl N-[(14R)-14-[5-[6-(difluoromethoxy)-2,3-difluorophenyl]-1-oxidopyridin-1-ium-2-yl]-17-methyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.15 nM	US-10214512
4-{[(2R)-2-{5-[5-chloro- 2-(1H-tetrazol-1- yl)phenyl]-1- oxidopyridin-2-yl}-3- phenylpropanoyl]amino} benzoic acid	IC50	0.16 nM	US-9783530: Factor Xla inhibitors
5-(3-chloro-2,6-difluorophenyl)-2-((5R,9S)-15-fluoro-24- ((methoxycarbonyl)amino)-5-methyl-4-oxo-3-aza-1(2,4)-pyridina-2(1,2)- benzenacyclononaphane-9-yl)pyridine 1-oxide	KI	0.16 nM	US-10214512

ChEMBL bioactivities

4505 potent at pChembl≥5 of 4636 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	Ki	0.02	nM	CHEMBL4096251
10.52	Ki	0.03	nM	CHEMBL4060950
10.52	Ki	0.03	nM	CHEMBL4107149
10.40	Ki	0.04	nM	CHEMBL3580759
10.40	Ki	0.04	nM	CHEMBL6039093
10.40	Ki	0.04	nM	CHEMBL4110926
10.30	Ki	0.05	nM	CHEMBL4112773
10.30	Ki	0.05	nM	CHEMBL4114881
10.22	Ki	0.06	nM	CHEMBL4097522
10.22	Ki	0.06	nM	CHEMBL4113483
10.22	Ki	0.06	nM	CHEMBL4109568
10.15	Ki	0.07	nM	CHEMBL4068445
10.15	Ki	0.07	nM	CHEMBL4083769
10.15	Ki	0.07	nM	CHEMBL5076656
10.15	IC50	0.07	nM	CHEMBL5934814
10.15	Ki	0.07	nM	CHEMBL4108033
10.10	Ki	0.08	nM	CHEMBL3260339
10.10	Ki	0.08	nM	CHEMBL6057268
10.10	Ki	0.08	nM	CHEMBL4115630
10.10	Ki	0.08	nM	CHEMBL4110983
10.05	Ki	0.09	nM	CHEMBL5778140
10.05	Ki	0.09	nM	CHEMBL5777512
10.05	Ki	0.09	nM	CHEMBL4111429
10.05	Ki	0.09	nM	CHEMBL4106708
10.05	Ki	0.09	nM	CHEMBL3948120
10.05	Ki	0.09	nM	CHEMBL4113824
10.01	Ki	0.098	nM	CHEMBL4097304
10.00	Ki	0.1	nM	CHEMBL3580759
10.00	Ki	0.1	nM	MILVEXIAN
10.00	Ki	0.1	nM	CHEMBL4107758
10.00	Ki	0.1	nM	CHEMBL4115014
10.00	Ki	0.1	nM	CHEMBL4113006
10.00	IC50	0.1	nM	CHEMBL5869576
10.00	Ki	0.1	nM	CHEMBL6034229
10.00	Ki	0.1	nM	CHEMBL5926090
10.00	Ki	0.1	nM	CHEMBL4114933
10.00	Ki	0.1	nM	CHEMBL4107808
9.96	Ki	0.11	nM	CHEMBL3260341
9.96	Ki	0.11	nM	MILVEXIAN
9.96	Ki	0.11	nM	CHEMBL5862641
9.96	Ki	0.11	nM	CHEMBL5934781
9.96	Ki	0.11	nM	CHEMBL4115423
9.92	Ki	0.12	nM	CHEMBL5094166
9.92	Ki	0.12	nM	CHEMBL5175227
9.92	Ki	0.12	nM	CHEMBL6001892
9.89	Ki	0.13	nM	CHEMBL4063677
9.89	Ki	0.13	nM	CHEMBL5204065
9.89	Ki	0.13	nM	CHEMBL5188215
9.89	Ki	0.13	nM	CHEMBL5813834
9.89	Ki	0.13	nM	CHEMBL5928310

PubChem BioAssay actives

929 with measured affinity, of 1471 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
methyl N-[(12E,15S)-18-chloro-15-[[(E)-3-[5-chloro-2-(tetrazol-1-yl)phenyl]prop-2-enoyl]amino]-9-oxo-8,17,19-triazatricyclo[14.2.1.02,7]nonadeca-1(18),2(7),3,5,12,16(19)-hexaen-5-yl]carbamate	1426857: Inhibition of human coagulation factor 11a using pyroGlu-Pro-Arg-pNA as substrate after 10 to 120 mins at 37 degC by spectrophotometric method	ki	<0.0001	uM
(E)-N-[(1S)-1-[5-chloro-4-(4-hydroxy-2-oxo-1H-quinolin-6-yl)-1H-imidazol-2-yl]-3-(4-methylpiperazin-1-yl)-3-oxopropyl]-3-[5-chloro-2-(tetrazol-1-yl)phenyl]prop-2-enamide	1229447: Inhibition of human coagulation factor 11a using p-nitroaniline as substrate assessed as substrate hydrolysis by spectrophotometry	ki	<0.0001	uM
methyl N-[(3S)-3-[[(E)-3-[5-chloro-2-(tetrazol-1-yl)phenyl]prop-2-enoyl]amino]-19-fluoro-15-oxo-5,14,22,23-tetrazatetracyclo[16.3.1.14,7.08,13]tricosa-1(22),4,6,8(13),9,11,18,20-octaen-11-yl]carbamate	1462590: Inhibition of human F11a using peptide substrate by spectrophotometry	ki	<0.0001	uM
(9R,13S)-13-[4-[5-chloro-2-(4-chlorotriazol-1-yl)phenyl]-6-oxopyrimidin-1-yl]-3-(difluoromethyl)-9-methyl-3,4,7,15-tetrazatricyclo[12.3.1.02,6]octadeca-1(18),2(6),4,14,16-pentaen-8-one	1817723: Binding affinity to human coagulation factor 11a using L-Pyroglutamyl-L-prolyl-L-arginine p-Nitroaniline as substrate assessed as inhibition constant measured upto 120 mins by spectrophotometric analysis	ki	0.0001	uM
(9R,13S)-13-[4-[5-chloro-2-(4-chlorotriazol-1-yl)phenyl]-6-oxo-2,3-dihydropyridin-1-yl]-3,9-dimethyl-3,4,7,15-tetrazatricyclo[12.3.1.02,6]octadeca-1(18),2(6),4,14,16-pentaen-8-one	1817723: Binding affinity to human coagulation factor 11a using L-Pyroglutamyl-L-prolyl-L-arginine p-Nitroaniline as substrate assessed as inhibition constant measured upto 120 mins by spectrophotometric analysis	ki	0.0001	uM
(9R,13S)-13-[4-[5-chloro-2-(4-chlorotriazol-1-yl)phenyl]-6-oxo-2,3-dihydropyridin-1-yl]-3-(difluoromethyl)-9-methyl-3,4,7,15-tetrazatricyclo[12.3.1.02,6]octadeca-1(18),2(6),4,14,16-pentaen-8-one	1817723: Binding affinity to human coagulation factor 11a using L-Pyroglutamyl-L-prolyl-L-arginine p-Nitroaniline as substrate assessed as inhibition constant measured upto 120 mins by spectrophotometric analysis	ki	0.0001	uM
3-[3-[4-[[(2S)-2-[[4-(aminomethyl)cyclohexanecarbonyl]amino]-3-[4-(5-methyl-2-propan-2-yl-1H-imidazo[4,5-b]pyridin-6-yl)phenyl]propanoyl]amino]phenyl]-1H-1,2,4-triazol-5-yl]-2,2,3,3-tetrafluoropropanoic acid	1558627: Inhibition of human factor 11a preincubated for 15 mins followed by Boc-Glu (OBzl) -Ala-Arg-AMC and measured after 30 mins by fluorescence method	ic50	0.0001	uM
methyl N-[(10R,14S)-17-chloro-14-[[(E)-3-[5-chloro-2-(tetrazol-1-yl)phenyl]prop-2-enoyl]amino]-10-methyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	1487595: Inhibition of human Factor XIa using S-2366 as chromogenic substrate after 60 mins by Lineweaver-Burk plot analysis	ki	0.0001	uM
methyl N-[(11R,12E,15S)-15-[[(E)-3-[5-chloro-2-(tetrazol-1-yl)phenyl]prop-2-enoyl]amino]-11-methyl-9-oxo-8,17,19-triazatricyclo[14.2.1.02,7]nonadeca-1(18),2(7),3,5,12,16-hexaen-5-yl]carbamate	1487595: Inhibition of human Factor XIa using S-2366 as chromogenic substrate after 60 mins by Lineweaver-Burk plot analysis	ki	0.0001	uM
4-[[(1S)-2-[(E)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(2-methyl-1-oxo-2,8-diazaspiro[4.5]decan-8-yl)-3,4-dihydro-1H-isoquinoline-1-carbonyl]amino]benzoic acid	1476844: Inhibition of human factor 11a using pyro-Glu-Pro-Arg-pNA as substrate at 37 degC after 10 to 120 mins by spectrophotometric method	ki	0.0001	uM
methyl N-[(10S,14S)-14-[[(E)-3-[5-chloro-2-(tetrazol-1-yl)phenyl]prop-2-enoyl]amino]-9-oxo-10-propan-2-yl-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15-pentaen-5-yl]carbamate	1487595: Inhibition of human Factor XIa using S-2366 as chromogenic substrate after 60 mins by Lineweaver-Burk plot analysis	ki	0.0001	uM
4-[[(1S)-2-[(E)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-[4-(dimethylamino)piperidin-1-yl]-3,4-dihydro-1H-isoquinoline-1-carbonyl]amino]benzoic acid	1476844: Inhibition of human factor 11a using pyro-Glu-Pro-Arg-pNA as substrate at 37 degC after 10 to 120 mins by spectrophotometric method	ki	0.0001	uM
methyl N-[(11S,15S)-18-chloro-15-[[(E)-3-[5-chloro-2-(tetrazol-1-yl)phenyl]prop-2-enoyl]amino]-11-methyl-9-oxo-8,17,19-triazatricyclo[14.2.1.02,7]nonadeca-1(18),2(7),3,5,16(19)-pentaen-5-yl]carbamate	1487595: Inhibition of human Factor XIa using S-2366 as chromogenic substrate after 60 mins by Lineweaver-Burk plot analysis	ki	0.0001	uM
5-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]-2-[(1R)-2-(4-fluorophenyl)-1-[4-(3-methyltriazol-4-yl)pyrazol-1-yl]ethyl]-1-oxidopyridin-1-ium	1885490: Inhibition of human coagulation factor XIa assessed as inhibition constant using 5FAM-Lys.Leu-Thr-Arg-Ala-Glu-Thr-Val-Lys(5Tamra)-amide as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by fluorescence based assay	ki	0.0001	uM
5-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]-2-[(1R)-3-methoxy-1-[4-(3-methyltriazol-4-yl)pyrazol-1-yl]propyl]-1-oxidopyridin-1-ium	1885490: Inhibition of human coagulation factor XIa assessed as inhibition constant using 5FAM-Lys.Leu-Thr-Arg-Ala-Glu-Thr-Val-Lys(5Tamra)-amide as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by fluorescence based assay	ki	0.0001	uM
5-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]-2-[(1R)-3-(difluoromethoxy)-1-[4-(3-methyltriazol-4-yl)pyrazol-1-yl]propyl]-1-oxidopyridin-1-ium	1885490: Inhibition of human coagulation factor XIa assessed as inhibition constant using 5FAM-Lys.Leu-Thr-Arg-Ala-Glu-Thr-Val-Lys(5Tamra)-amide as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by fluorescence based assay	ki	0.0001	uM
methyl N-[(10R,14S)-14-[4-(6-bromo-3-chloro-2-fluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	1137957: Inhibition of human coagulation factor 11a after 20 to 180 mins	ki	0.0001	uM
methyl N-[(10R,14S)-14-[4-(3-chloro-2,6-difluorophenyl)-2-oxo-1-pyridinyl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	1137957: Inhibition of human coagulation factor 11a after 20 to 180 mins	ki	0.0001	uM
2-[3-(6-carbamimidoyl-4-methyl-4-phenyl-2,3-dihydro-1H-quinolin-2-yl)-5-(3-methylbutanoylamino)phenyl]-5-carbamoylbenzoic acid	1074192: Binding affinity to human factor 11a assessed as release of p-nitroaniline after 10 to 120 mins by spectrophotometric analysis	ki	0.0002	uM
(9R,13S)-13-[4-[5-chloro-2-(4-chlorotriazol-1-yl)phenyl]-6-oxopyrimidin-1-yl]-3,9-dimethyl-3,4,7,15-tetrazatricyclo[12.3.1.02,6]octadeca-1(18),2(6),4,14,16-pentaen-8-one	1817723: Binding affinity to human coagulation factor 11a using L-Pyroglutamyl-L-prolyl-L-arginine p-Nitroaniline as substrate assessed as inhibition constant measured upto 120 mins by spectrophotometric analysis	ki	0.0002	uM
methyl N-[(10R,14S)-14-[[(E)-3-[5-chloro-2-(tetrazol-1-yl)phenyl]prop-2-enoyl]amino]-10-ethyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15-pentaen-5-yl]carbamate	1487595: Inhibition of human Factor XIa using S-2366 as chromogenic substrate after 60 mins by Lineweaver-Burk plot analysis	ki	0.0002	uM
methyl N-[(10R,14S)-14-[[(E)-3-[5-chloro-2-(tetrazol-1-yl)phenyl]prop-2-enoyl]amino]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate;2,2,2-trifluoroacetic acid	1559640: Inhibition of human activated factor XI using pyro-Glu-Pro-Arg-pNA as substrate by spectrophotometry	ki	0.0002	uM
methyl N-[(10R,14S)-14-[[(E)-3-[5-chloro-2-(tetrazol-1-yl)phenyl]prop-2-enoyl]amino]-10-ethyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	1559640: Inhibition of human activated factor XI using pyro-Glu-Pro-Arg-pNA as substrate by spectrophotometry	ki	0.0002	uM
ethyl (14R)-14-[5-(3-chloro-2-fluorophenyl)-1-oxidopyridin-1-ium-2-yl]-5-(methoxycarbonylamino)-10,10-dimethyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaene-17-carboxylate	1865533: Inhibition of human coagulation factor XIa using GPR-AFC as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by fluorescence assay	ic50	0.0002	uM
5-[3-chloro-6-(4-chlorotriazol-1-yl)-2-fluorophenyl]-2-[(1R)-3-(difluoromethoxy)-1-[4-(3-methyltriazol-4-yl)pyrazol-1-yl]propyl]-1-oxidopyridin-1-ium	1885490: Inhibition of human coagulation factor XIa assessed as inhibition constant using 5FAM-Lys.Leu-Thr-Arg-Ala-Glu-Thr-Val-Lys(5Tamra)-amide as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by fluorescence based assay	ki	0.0002	uM
5-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]-2-[(1R)-2-cyclopropyl-1-[4-(3-methyltriazol-4-yl)pyrazol-1-yl]ethyl]-1-oxidopyridin-1-ium	1885490: Inhibition of human coagulation factor XIa assessed as inhibition constant using 5FAM-Lys.Leu-Thr-Arg-Ala-Glu-Thr-Val-Lys(5Tamra)-amide as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by fluorescence based assay	ki	0.0002	uM
5-[3-chloro-6-(4-chlorotriazol-1-yl)-2-fluorophenyl]-2-[(1R)-2-(4-fluorophenyl)-1-[4-(3-methyltriazol-4-yl)pyrazol-1-yl]ethyl]-1-oxidopyridin-1-ium	1885490: Inhibition of human coagulation factor XIa assessed as inhibition constant using 5FAM-Lys.Leu-Thr-Arg-Ala-Glu-Thr-Val-Lys(5Tamra)-amide as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by fluorescence based assay	ki	0.0002	uM
azane;(14R)-14-[5-[2-(difluoromethoxy)-5-fluorophenyl]-1-oxidopyridin-1-ium-2-yl]-5-(methoxycarbonylamino)-10,10-dimethyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaene-17-carboxylic acid	1865533: Inhibition of human coagulation factor XIa using GPR-AFC as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by fluorescence assay	ic50	0.0002	uM
(E)-N-[(1S)-1-[5-chloro-4-(4-hydroxy-2-oxo-1H-quinolin-6-yl)-1H-imidazol-2-yl]-2-phenylethyl]-3-[5-chloro-2-(tetrazol-1-yl)phenyl]prop-2-enamide	1229447: Inhibition of human coagulation factor 11a using p-nitroaniline as substrate assessed as substrate hydrolysis by spectrophotometry	ki	0.0002	uM
2-[3-[(2S,4R)-6-carbamimidoyl-4-methyl-4-phenyl-2,3-dihydro-1H-quinolin-2-yl]-5-(3-methylbutanoylamino)phenyl]-5-carbamoylbenzoic acid	1171256: Inhibition of human coagulation factor 11a using p-nitroaniline as substrate assessed as substrate hydrolysis by spectrophotometrically	ki	0.0002	uM
methyl N-[(12E,15S)-15-[[(E)-3-[5-chloro-2-(tetrazol-1-yl)phenyl]prop-2-enoyl]amino]-9-oxo-8,17,19-triazatricyclo[14.2.1.02,7]nonadeca-1(18),2(7),3,5,12,16-hexaen-5-yl]carbamate	1426857: Inhibition of human coagulation factor 11a using pyroGlu-Pro-Arg-pNA as substrate after 10 to 120 mins at 37 degC by spectrophotometric method	ki	0.0002	uM
ethyl (9R,14S)-14-[[(E)-3-[5-chloro-2-(tetrazol-1-yl)phenyl]prop-2-enoyl]amino]-5-(methoxycarbonylamino)-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15-pentaene-9-carboxylate	1651396: Inhibition of recombinant human activated coagulation factor XI using pyro-Glu-Pro-Arg-pNA as substrate by spectrophotometry	ki	0.0002	uM
N-[(1S)-1-[4-(3-amino-1H-indazol-6-yl)-5-chloro-1H-imidazol-2-yl]-2-phenylethyl]-4-(aminomethyl)cyclohexane-1-carboxamide	1192250: Inhibition of human coagulation factor 11a at 25 degC	ki	0.0003	uM
3-[3-[4-[[(2S)-2-[[4-(aminomethyl)cyclohexanecarbonyl]amino]-3-[4-(6-methyl-2-propan-2-yl-1H-benzimidazol-5-yl)phenyl]propanoyl]amino]phenyl]-1H-1,2,4-triazol-5-yl]-2,2,3,3-tetrafluoropropanoic acid	1558627: Inhibition of human factor 11a preincubated for 15 mins followed by Boc-Glu (OBzl) -Ala-Arg-AMC and measured after 30 mins by fluorescence method	ic50	0.0003	uM
methyl N-[4-[2-[1-[5-[5-chloro-2-(tetrazol-1-yl)phenyl]-1-oxidopyridin-1-ium-2-yl]-2-cyclopropylethyl]-1H-imidazol-5-yl]phenyl]carbamate	1885490: Inhibition of human coagulation factor XIa assessed as inhibition constant using 5FAM-Lys.Leu-Thr-Arg-Ala-Glu-Thr-Val-Lys(5Tamra)-amide as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by fluorescence based assay	ki	0.0003	uM
N-[(1S)-1-[4-(3-amino-1H-indazol-6-yl)-5-chloro-1H-imidazol-2-yl]-2-phenylethyl]-4-(aminomethyl)cyclohexane-1-carboxamide;2,2,2-trifluoroacetic acid	1171256: Inhibition of human coagulation factor 11a using p-nitroaniline as substrate assessed as substrate hydrolysis by spectrophotometrically	ki	0.0003	uM
N-[(1S)-1-[4-(3-amino-1H-indazol-6-yl)-5-fluoro-1H-imidazol-2-yl]-2-phenylethyl]-4-(aminomethyl)cyclohexane-1-carboxamide;2,2,2-trifluoroacetic acid	1171256: Inhibition of human coagulation factor 11a using p-nitroaniline as substrate assessed as substrate hydrolysis by spectrophotometrically	ki	0.0003	uM
2-[4-[5-chloro-2-(tetrazol-1-yl)phenyl]-5-methoxy-2-oxo-1-pyridinyl]-4-methoxy-N-(2-methylindazol-5-yl)butanamide	2013733: Inhibition of human FXIa using Boc-Glu(OBzl)-Ala-Arg-AMC as substrate measured for 30 mins by fluorometric assay	ic50	0.0003	uM
methyl N-[(12E,15S)-15-[[(E)-3-[5-chloro-2-(tetrazol-1-yl)phenyl]prop-2-enoyl]amino]-10-methyl-9-oxo-8,17,19-triazatricyclo[14.2.1.02,7]nonadeca-1(18),2(7),3,5,12,16-hexaen-5-yl]carbamate	1487595: Inhibition of human Factor XIa using S-2366 as chromogenic substrate after 60 mins by Lineweaver-Burk plot analysis	ki	0.0003	uM
methyl N-[(14S)-14-[[4-(aminomethyl)cyclohexanecarbonyl]amino]-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15-pentaen-5-yl]carbamate	1384604: Inhibition of human factor 11a incubated for 60 mins by Cheng-Prusoff equation analysis	ki	0.0003	uM
methyl N-[(12E,15S)-18-chloro-15-[(6R)-6-(3-chloro-2,6-difluorophenyl)-6-deuterio-2-oxo-1,3-oxazinan-3-yl]-9-oxo-8,17,19-triazatricyclo[14.2.1.02,7]nonadeca-1(18),2(7),3,5,12,16(19)-hexaen-5-yl]carbamate	1601095: Inhibition of activated human coagulation factor 11 using pyroGlu-Pro-Arg-pNA as substrate incubated for 10 to 120 mins by spectrofluorometric method	ki	0.0003	uM
(14R)-14-[5-(3-chloro-2-fluorophenyl)-1-oxidopyridin-1-ium-2-yl]-5-(methoxycarbonylamino)-10,10-dimethyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaene-17-carboxylic acid	1865533: Inhibition of human coagulation factor XIa using GPR-AFC as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by fluorescence assay	ic50	0.0003	uM
ethyl (14R)-14-[5-[2-(difluoromethoxy)-5-fluorophenyl]-1-oxidopyridin-1-ium-2-yl]-5-(methoxycarbonylamino)-10,10-dimethyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaene-17-carboxylate	1865533: Inhibition of human coagulation factor XIa using GPR-AFC as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by fluorescence assay	ic50	0.0003	uM
5-[3-chloro-2-fluoro-6-[4-(trifluoromethyl)triazol-1-yl]phenyl]-2-[(1R)-2-[1-(difluoromethyl)pyrazol-3-yl]-1-[4-(3-methyltriazol-4-yl)pyrazol-1-yl]ethyl]-1-oxidopyridin-1-ium	1885490: Inhibition of human coagulation factor XIa assessed as inhibition constant using 5FAM-Lys.Leu-Thr-Arg-Ala-Glu-Thr-Val-Lys(5Tamra)-amide as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by fluorescence based assay	ki	0.0003	uM
5-[3-chloro-2-fluoro-6-[4-(trifluoromethyl)triazol-1-yl]phenyl]-2-[(1R)-3-(difluoromethoxy)-1-[4-(3-methyltriazol-4-yl)pyrazol-1-yl]propyl]-1-oxidopyridin-1-ium	1885490: Inhibition of human coagulation factor XIa assessed as inhibition constant using 5FAM-Lys.Leu-Thr-Arg-Ala-Glu-Thr-Val-Lys(5Tamra)-amide as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by fluorescence based assay	ki	0.0003	uM
5-[1-[1-[5-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]-1-oxidopyridin-1-ium-2-yl]-2-cyclopropylethyl]pyrazol-4-yl]-4-methyl-1,3-thiazole	1885490: Inhibition of human coagulation factor XIa assessed as inhibition constant using 5FAM-Lys.Leu-Thr-Arg-Ala-Glu-Thr-Val-Lys(5Tamra)-amide as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by fluorescence based assay	ki	0.0003	uM
6-chloro-5-[2-[(1R)-1-[5-[5-chloro-2-(tetrazol-1-yl)phenyl]-1-oxidopyridin-1-ium-2-yl]-2-cyclopropylethyl]-1H-imidazol-5-yl]pyridin-2-amine	1987633: Inhibition of FXIa (unknown origin)	ic50	0.0003	uM
methyl N-[4-[2-[(1R)-1-[5-[5-chloro-2-(tetrazol-1-yl)phenyl]-1-oxidopyridin-1-ium-2-yl]-2-cyclopropylethyl]-1H-imidazol-5-yl]phenyl]carbamate	1987658: Binding affinity to FXIa (unknown origin) assessed as inhibition constant	ki	0.0003	uM
4-[[(2S)-2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxo-1-pyridinyl]-3-(4-hydroxycyclohexyl)propanoyl]amino]benzoic acid	2013733: Inhibition of human FXIa using Boc-Glu(OBzl)-Ala-Arg-AMC as substrate measured for 30 mins by fluorometric assay	ic50	0.0003	uM
1-[[4-(6-amino-2-fluoro-3-pyridinyl)-5-fluoro-1H-imidazol-2-yl]methyl]-4-[5-chloro-2-(tetrazol-1-yl)phenyl]-6,7-dihydrocyclopenta[b]pyridine-2,5-dione	1987633: Inhibition of FXIa (unknown origin)	ic50	0.0003	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	4
Tetrachlorodibenzodioxin	increases expression	4
Cyclosporine	decreases expression	3
bisphenol A	affects expression, decreases methylation	2
sodium arsenite	decreases expression, affects methylation	2
perfluorooctane sulfonic acid	decreases expression	2
Acetaminophen	decreases expression	2
Cadmium	decreases expression, affects binding	2
Aflatoxin B1	affects expression, decreases expression	2
dicrotophos	decreases expression	1
methyleugenol	decreases expression	1
titanium dioxide	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
S 2366	affects metabolic processing	1
perfluoro-n-nonanoic acid	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, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Vorinostat	affects cotreatment, decreases expression	1
Angiotensin-Converting Enzyme Inhibitors	decreases expression	1
Calcium Chloride	affects cotreatment, increases activity	1
Estradiol	decreases expression	1
Iodoacetamide	increases cleavage	1
Kaolin	decreases activity	1
N-Nitrosopyrrolidine	decreases expression	1
Urethane	decreases expression	1

ChEMBL screening assays

273 unique, capped per target: 272 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1005617	Binding	Inhibition of human factor 11a	Factor VIIa inhibitors: target hopping in the serine protease family using X-ray structure determination. — Bioorg Med Chem Lett
CHEMBL4305266	ADMET	Inhibition of factor 11a (unknown origin) using S-2366 as substrate preincubated for 5 mins followed by substrate addition	On the Process of Discovering Leads That Target the Heparin-Binding Site of Neutrophil Elastase in the Sputum of Cystic Fibrosis Patients. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00039858	PHASE4	COMPLETED	Evaluation of Argatroban Injection in Pediatric Patients Requiring Anticoagulant Alternatives to Heparin
NCT00239733	PHASE4	TERMINATED	Anti-D for Treating Thrombocytopenia in Adults Infected With Hepatitis C Virus With or Without HIV Co-Infection
NCT00907478	PHASE4	COMPLETED	Study on Bone Marrow Morphology in Adults Receiving Romiplostim for Treatment of Thrombocytopenia Associated With Immune Thrombocytopenia Purpura (ITP)
NCT01727401	PHASE4	TERMINATED	Thromboprophylaxis of Venous Thromboembolism in Acutely-ill Medical Inpatients With Thrombocytopenia
NCT02032134	PHASE4	TERMINATED	Protocol for the Infusion of Buffy Coat-derived Cryopreserved Platelets in Patients With Severe Thrombocytopenia
NCT02267993	PHASE4	COMPLETED	Efficacy and Safety of rhTPO for the Treatment of Thrombocytopenia After Chemotherapy in AML Patients
NCT03633019	PHASE4	UNKNOWN	High-dose Use of rhTPO in CIT Patients
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04906083	PHASE4	UNKNOWN	Avatrombopag in Patients With End-stage Liver Disease and Thrombocytopenia
NCT05217719	PHASE4	UNKNOWN	Effects of Recombinant Human Thrombopoietin on Platelet Levels in ICU Patients
NCT05255003	PHASE4	RECRUITING	STrategies for Anticoagulation in Patients With thRombocytopenia and Cancer-associated Thrombosis
NCT05382013	PHASE4	UNKNOWN	Efficacy and Safety of Avatrombopag for Treating TCP in HBV-ACLF Patients Receiving ALSS Treatment
NCT05944458	PHASE4	COMPLETED	Efficacy of Intravenous N-Acetylcysteine in Preventing Linezolid-Induced Thrombocytopenia in Critically Ill Patients
NCT06562738	PHASE4	RECRUITING	Clinical Study on Efficacy and Safety of Hetrombopag in the Preoperative Patients of Thrombocytopenia
NCT00037791	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00039910	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00073580	PHASE3	COMPLETED	Angiomax in Patients With HIT/HITTS Type II Undergoing Off-Pump Coronary Artery Bypass Grafting (CABG) (CHOOSE)
NCT00102323	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Refractory to Splenectomy
NCT00102336	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Prior to Splenectomy
NCT00116688	PHASE3	COMPLETED	Open Label Extension Study of Romiplostim (AMG 531) in Thrombocytopenic Patients With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
NCT00128713	PHASE3	COMPLETED	Optimal Platelet Dose Strategy for Management of Thrombocytopenia
NCT00151866	PHASE3	COMPLETED	Efficacy of Transfusions With Platelets Stored in Platelet Additive Solution II Versus Plasma
NCT00261924	PHASE3	COMPLETED	Efficacy and Safety Study of Platelets Treated for Pathogen Inactivation and Stored for Up to Seven Days
NCT00415532	PHASE3	COMPLETED	Romiplostim (AMG 531) Versus Medical Standard of Care for Immune (Idiopathic) Thrombocytopenic Purpura
NCT00420914	PHASE3	TERMINATED	Strategies for Transfusion of Platelets (SToP)
NCT00501345	PHASE3	TERMINATED	Aspirin in Patients With Myocardial Infarction and Thrombocytopenia
NCT00508820	PHASE3	COMPLETED	An Open Label Study of Romiplostim in Adult Thrombocytopenic Subjects With ITP
NCT00678587	PHASE3	TERMINATED	Eltrombopag To Reduce The Need For Platelet Transfusion In Subjects With Chronic Liver Disease And Thrombocytopenia Undergoing Elective Invasive Procedures
NCT01438840	PHASE3	COMPLETED	Efficacy and Safety of Oral E5501 Plus Standard of Care for the Treatment of Thrombocytopenia in Adults With Chronic Immune Thrombocytopenia (Amendment 02)
NCT01444417	PHASE3	COMPLETED	Safety and Efficacy Study of Romiplostim to Treat Immune Thrombocytopenia (ITP) in Pediatric Patients
NCT01805648	PHASE3	UNKNOWN	Efficacy and Safety Study of Maintenance Treatment With rhTPO in Thrombocytopenic Subjects With ITP
NCT02244658	PHASE3	UNKNOWN	Recombinant Human Thrombopoietin (rhTPO) in Management of Chemotherapy-induced Thrombocytopenia in Acute Myelocytic Leukemia
NCT02389621	PHASE3	COMPLETED	Safety and Efficacy Study of Lusutrombopag for Thrombocytopenia in Patients With Chronic Liver Disease Undergoing Elective Invasive Procedures
NCT02444728	PHASE3	TERMINATED	Cyclophosphamide and Hydroxychloroquine for Thrombocytopenia in SLE
NCT02487563	PHASE3	COMPLETED	Prospective Study of Patients With Thrombocytopenia Following HSCT
NCT02578901	PHASE3	COMPLETED	American Trial Using Tranexamic Acid in Thrombocytopenia
NCT03326843	PHASE3	TERMINATED	Avatrombopag for the Treatment of Thrombocytopenia in Adults Scheduled for a Surgical Procedure
NCT03515096	PHASE3	COMPLETED	Eltrombopag vs. rhTPO to Increase Platelet Level After HSCT
NCT05563064	PHASE3	UNKNOWN	Effect of Herbal Formulation on Thrombocytes Count
NCT07442513	PHASE3	RECRUITING	Comparison of Etamsylate Versus Placebo to Prevent Bleeding in HSCT