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F12

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Summary

F12 (coagulation factor XII, HGNC:3530) is a protein-coding gene on chromosome 5q35.3, encoding Coagulation factor XII (P00748). Factor XII is a serum glycoprotein that participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin.

This gene encodes coagulation factor XII which circulates in blood as a zymogen. This single chain zymogen is converted to a two-chain serine protease with an heavy chain (alpha-factor XIIa) and a light chain. The heavy chain contains two fibronectin-type domains, two epidermal growth factor (EGF)-like domains, a kringle domain and a proline-rich domain, whereas the light chain contains only a catalytic domain. On activation, further cleavages takes place in the heavy chain, resulting in the production of beta-factor XIIa light chain and the alpha-factor XIIa light chain becomes beta-factor XIIa heavy chain. Prekallikrein is cleaved by factor XII to form kallikrein, which then cleaves factor XII first to alpha-factor XIIa and then to beta-factor XIIa. The active factor XIIa participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. It activates coagulation factors VII and XI. Defects in this gene do not cause any clinical symptoms and the sole effect is that whole-blood clotting time is prolonged.

Source: NCBI Gene 2161 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): congenital factor XII deficiency (Definitive, ClinGen) — +1 more curated relationship
  • GWAS associations: 24
  • Clinical variants (ClinVar): 248 total — 8 pathogenic, 9 likely-pathogenic
  • Phenotypes (HPO): 19
  • Druggable target: yes — 3 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_000505

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:3530
Approved symbolF12
Namecoagulation factor XII
Location5q35.3
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000131187
Ensembl biotypeprotein_coding
OMIM610619
Entrez2161

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 10 protein_coding, 6 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000253496, ENST00000502854, ENST00000503736, ENST00000504406, ENST00000510358, ENST00000514943, ENST00000696192, ENST00000696193, ENST00000696194, ENST00000696195, ENST00000696200, ENST00000696201, ENST00000898122, ENST00000898123, ENST00000898124, ENST00000898125, ENST00000898126, ENST00000898127, ENST00000898128, ENST00000898129

RefSeq mRNA: 1 — MANE Select: NM_000505 NM_000505

CCDS: CCDS34302

Canonical transcript exons

ENST00000253496 — 14 exons

ExonStartEnd
ENSE00003966402177403481177403617
ENSE00003966421177403859177404090
ENSE00003966422177404196177404413
ENSE00003966423177402141177402459
ENSE00003966424177404499177404664
ENSE00003966425177405962177406061
ENSE00003966429177405735177405805
ENSE00003966430177405054177405185
ENSE00003966431177402550177402698
ENSE00003966432177409471177409564
ENSE00003966433177409046177409103
ENSE00003966434177404810177404914
ENSE00003966435177405323177405433
ENSE00003966436177403254177403397

Expression profiles

Bgee: expression breadth ubiquitous, 191 present calls, max score 99.36.

FANTOM5 (CAGE): breadth broad, TPM avg 3.0033 / max 700.9392, expressed in 627 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter IDTPM avgSamples expressed
650901.480915
650880.8596422
650870.3978238
650860.126059
650890.090623
650910.04838

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
right lobe of liverUBERON:000111499.36gold quality
liverUBERON:000210798.71gold quality
gingival epitheliumUBERON:000194992.35gold quality
gingivaUBERON:000182890.22gold quality
lower esophagus mucosaUBERON:003583488.25gold quality
mucosa of transverse colonUBERON:000499188.09gold quality
cervix squamous epitheliumUBERON:000692287.70silver quality
squamous epitheliumUBERON:000691484.61gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047384.10gold quality
esophagus mucosaUBERON:000246983.77gold quality
endothelial cellCL:000011583.75gold quality
middle temporal gyrusUBERON:000277183.42gold quality
epithelium of esophagusUBERON:000197681.02gold quality
tongue squamous epitheliumUBERON:000691980.99silver quality
nucleus accumbensUBERON:000188280.69gold quality
esophagus squamous epitheliumUBERON:000692080.68gold quality
cervix epitheliumUBERON:000480179.03silver quality
caudate nucleusUBERON:000187378.45gold quality
putamenUBERON:000187477.59gold quality
Brodmann (1909) area 23UBERON:001355477.02gold quality
pancreatic ductal cellCL:000207976.97silver quality
prefrontal cortexUBERON:000045176.96gold quality
oral cavityUBERON:000016776.92gold quality
mammalian vulvaUBERON:000099776.74gold quality
skin of abdomenUBERON:000141676.68gold quality
skin of legUBERON:000151176.11gold quality
Brodmann (1909) area 9UBERON:001354075.82gold quality
zone of skinUBERON:000001475.44gold quality
right frontal lobeUBERON:000281075.31gold quality
cingulate cortexUBERON:000302774.96gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes5.55
E-HCAD-13no3.05

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EPAS1, ESR1, HNF4A, SMAD3, SPI1, VSX2

miRNA regulators (miRDB)

14 targeting F12, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-7110-3P100.0073.182486
HSA-MIR-477999.8666.501583
HSA-MIR-6739-5P99.8067.872806
HSA-MIR-6733-5P99.7467.942759
HSA-MIR-7157-5P99.6669.331829
HSA-MIR-1249-5P99.6166.552049
HSA-MIR-6797-5P99.6166.552084
HSA-MIR-431099.5968.842527
HSA-MIR-315399.5567.592337
HSA-MIR-127599.4767.902749
HSA-MIR-330-3P99.4169.952521
HSA-MIR-429798.7766.952013
HSA-MIR-63797.9164.051517
HSA-MIR-5581-5P97.9166.50965

Literature-anchored findings (GeneRIF, showing 40)

  • 2 unrelated factor XII-deficient Japanese families had 2 new mutations: a heterozygous Q421K with reduced FXII activity and a severe homozygous mutation (R123P). (PMID:11776307)
  • Heat shock protein 90 catalyzes activation of the prekallikrein-kininogen complex in the absence of factor XII. (PMID:11792853)
  • linkage mapping; quantitative-trait locus in the human factor XII gene influences both plasma factor XII levels and susceptibility to thrombotic disease (PMID:11805911)
  • The TT genotype of the FXII 46C>T polymorphism is associated with a high risk of CHD in men with high cholesterol. (PMID:12208481)
  • This supports the hypothesis that binding to endothelial cells protects the activated FXII against inactivation by its major endogenous inhibitor. Hence, the function of FXII may be localized at cellular surfaces. (PMID:12492481)
  • A homozygous substitution of G to C at 10587 (cDNA position 1458) in the FXII gene results in a Trp to Cys substitution in the catalytic domain. Reduced secretion of FXII protein was due to incorrect folding caused by the introduction of Cys486. (PMID:12876626)
  • factor XII binds to lung & dermal microvascular endothelial cells and astrocytes in a saturable and Zn(+2) dependent manner, which may serve to concentrate proteins binding to high molecular weight kininogen. (PMID:14597972)
  • the 46C–>T polymorphism itself is an independent risk factor for venous thrombosis in the Spanish population (PMID:15116249)
  • The role played by FXII deficiency in the pathogenesis of venous thrombosis is minor, if any. (PMID:15306750)
  • similar FXIIa levels in acute or chronic phases of coronary atherosclerosis suggests that the initial arterial denudation and acute-phase response associated to acute coronary syndromes are not major determinants for prolonged FXII activation (PMID:15567455)
  • An amino acid substitution in F12 was discovered and characterized in an elderly Japanese male. (PMID:15617741)
  • allele-specific dosage-dependent effect of the 46T-allele on plasma FXII levels (PMID:15748262)
  • cross-reacting material is present in approximately 5% of homozygote patients. More precisely, seven of 145 patients. Only in one case, the was antigen level normal (FXII (PMID:16015420)
  • Sotos syndrome is a contiguous gene syndrome incorporating coagulation factor twelve (FXII) deficiency (PMID:16170239)
  • results suggest that HK interferes with the binding of FXII to sulfatides and thereby the autoactivation of FXII. The binding of activated FXII to the ECM suggests that FXIIa may be a modulator of cellular adhesion, migration and vascularization. (PMID:16493494)
  • Two different missense mutations were identified in exactly the same position within exon 9 of the F12 gene in patient with angioedema. (PMID:16638441)
  • homozygosity for the C46T polymorphism of the F12 gene may have a role in venous thrombosis during the first pregnancy/puerperium in previously asymptomatic women (PMID:17408404)
  • Factor XII impairs arterial thrombus formation but is not associated with excessive bleeding.Factor XII selectively contributes to thrombus formation in occlusive disease but not in normal hemostasis. (PMID:17605651)
  • study reports hereditary angioedema with normal C1 inhibitor gene in a family associated with the p.Thr328Lys mutation in the F12 gene (PMID:17825897)
  • No significant differences are observed in genotype and mutant allele frequencies of the FXII C46T polymorphism between mouth caner patients and healthy controls. (PMID:17982641)
  • Lower FXII activity represents an independent risk for CHD and ACS. This is not the case for FXIIa levels or the FXII 46C>T variation. (PMID:18021303)
  • Identified 15 genetic variants; the deficiency was caused by 5281delG in exon 9 of Patient 1; the 6306delG in exon 12 and deletion of 23 bp in intron 8 of Patient 2, and a G-8C transversion in Patient 3 (PMID:18024408)
  • The TT genotype of the functional factor XII C46T gene polymorphism may be a new independent risk factor for cerebral venous thrombosis (CVT). (PMID:18180442)
  • Used synthetic peptides in inhibition and direct binding studies to identify the antigenic binding site of autoantibodies to FXII in patients with recurrent pregnancy loss. (PMID:18278180)
  • Sulfated galactan from the red alga Botryocladia occidentalis induces factor XII activation. (PMID:18327401)
  • The dimeric structure of FXI is essential for normal proteolytic activation of FXI by FXIIa, thrombin, or FXIa either in solution or on an anionic surface but not for FIX activation by FXIa in solution. (PMID:18441012)
  • A novel mutation in a patient with congenital coagulation factor XII deficiency. (PMID:18710647)
  • factor XII is activated by misfolded proteins in humans, leading to kallikrein formation without initiating coagulation (PMID:18725990)
  • thrombin is activated by prothrombinase and interacts with sufficiently poor affinity with F12 so that it is rapidly released from its site of production to participate in its numerous hemostatic functions (PMID:18765660)
  • FXIIa, but not FXII, binds in a Zn2+-independent manner to immobilized FN through the type I repeat modules. (PMID:18793325)
  • factor XII deficiency: a report of three new mutations exon 13 (Q501STOP), exon 14 (P547L) and -13C>T promoter region in three compound heterozygotes (PMID:18832903)
  • These results support that the mentioned mutation in factor XII gene causes hereditary angioedema type III. (PMID:19178407)
  • missense mutation in F12 is present in 3 affected females of a family with estrogen-dependent inherited angioedema; affected females have polymorphisms associated with lower levels of APP & ACE; study suggests multiple genes may contribute to this disease (PMID:19178938)
  • The F12 46C –> T gene polymorphism is not related to CAD in the studied population. (PMID:19204433)
  • Includes the study of a polymorphic upstream ORF in this gene, and shows that it functions to reduce protein levels by ~50%. (PMID:19372376)
  • 1st report of molecular genotype of hemophilia A in the Saudi population: the intron 22 inversion was seen in 10 patients; 5 point mutations (1 new:R593P) & a new deletion/insertion involving different exons were detected. (PMID:19448530)
  • Contrary to the results of a recently published study, no indication that the Thr309Lys mutation causes a ‘gain-of-function’ of FXIIa was observed in this investigation. (PMID:19474702)
  • Thirty-five female patients with hereditary angioedema and the factor XII mutations p.Thr309Lys and p.Thr309Arg who came from 13 unrelated families were studied, but no difference between mutation p.Thr309Arg and p.Thr309Lys was found (PMID:19477491)
  • A common functional polymorphism in the promoter of the FXII gene (F12-4C>T) is not associated with peripheral arterial disease. (PMID:19625260)
  • there is an important subtype of hereditary angioedema (HAE), designated type III HAE, which is associated with pathogenic mutations in the F12 gene. (PMID:19647418)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_reriof9aENSDARG00000010097
mus_musculusF12ENSMUSG00000021492
rattus_norvegicusF12ENSRNOG00000015139

Paralogs (16): F7 (ENSG00000057593), F11 (ENSG00000088926), F9 (ENSG00000101981), HGFAC (ENSG00000109758), F10 (ENSG00000126218), KLK10 (ENSG00000129451), 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 XII — P00748 (reviewed: P00748)

Alternative names: Hageman factor

All UniProt accessions (5): A0A8Q3WL25, A0A8Q3WL28, A0A8Q3WL35, A0A8Q3WL37, P00748

UniProt curated annotations — full annotation on UniProt →

Function. Factor XII is a serum glycoprotein that participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. Prekallikrein is cleaved by factor XII to form kallikrein, which then cleaves factor XII first to alpha-factor XIIa and then trypsin cleaves it to beta-factor XIIa. Alpha-factor XIIa activates factor XI to factor XIa.

Subunit / interactions. Interacts with HRG; the interaction, which is enhanced in the presence of zinc ions and inhibited by heparin-binding, inhibits factor XII autoactivation and contact-initiated coagulation. Interacts (inactive and activated) with D7L2, an anticoagulant protein from Anopheles gambiae. Interacts (activated) with iripin-8, a serine protease inhibitor from Ixodes ricinus saliva. Interacts (inactive and activated) (via amino acids 1-77) with triafestin-1 and triafestin-2, anticoagulant proteins from Triatoma infestans. Interacts (inactive and activated) (via amino acids 1-77) with short form salivary protein D7R1, an anticoagulant protein from Anopheles stephensi. Interacts (inactive and activated) (via fibronectin type II domain) with haemaphysalin, an anticoagulant protein from Haemaphysalis longicornis.

Subcellular location. Secreted.

Post-translational modifications. Factor XII is activated by kallikrein in alpha-factor XIIa, which is further converted by trypsin into beta-factor XIIa. Alpha-factor XIIa is composed of an NH2-terminal heavy chain, called coagulation factor XIIa heavy chain, and a COOH-terminal light chain, called coagulation factor XIIa light chain, connected by a disulfide bond. Beta-factor XIIa is composed of 2 chains linked by a disulfide bond, an N-terminal nonapeptide, called beta-factor XIIa part 1, and coagulation factor XIIa light chain, also known in this context as beta-factor XIIa part 2. O- and N-glycosylated. The O-linked polysaccharides were not identified, but are probably the mucin type linked to GalNAc.

Disease relevance. Factor XII deficiency (FA12D) [MIM:234000] An asymptomatic anomaly of in vitro blood coagulation. Its diagnosis is based on finding a low plasma activity of the factor in coagulating assays. It is usually only accidentally discovered through pre-operative blood tests. Factor XII deficiency is divided into two categories, a cross-reacting material (CRM)-negative group (negative F12 antigen detection) and a CRM-positive group (positive F12 antigen detection). The disease is caused by variants affecting the gene represented in this entry. Angioedema, hereditary, 3 (HAE3) [MIM:610618] A hereditary angioedema occurring only in women. Hereditary angioedema is an autosomal dominant disorder characterized by episodic local swelling involving subcutaneous or submucous tissue of the upper respiratory and gastrointestinal tracts, face, extremities, and genitalia. Hereditary angioedema type 3 differs from types 1 and 2 in that both concentration and function of C1 esterase inhibitor are normal. Hereditary angioedema type 3 is precipitated or worsened by high estrogen levels (e.g., during pregnancy or treatment with oral contraceptives). The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activity is promoted in the presence of negatively charged surfaces.

Similarity. Belongs to the peptidase S1 family.

RefSeq proteins (1): NP_000496* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000001KringleDomain
IPR000083Fibronectin_type1Domain
IPR000562FN_type2_domDomain
IPR000742EGFDomain
IPR001254Trypsin_domDomain
IPR001314Peptidase_S1AFamily
IPR001881EGF-like_Ca-bd_domDomain
IPR009003Peptidase_S1_PAHomologous_superfamily
IPR013806Kringle-likeHomologous_superfamily
IPR014394Coagulation_fac_XII/HGFAFamily
IPR018056Kringle_CSConserved_site
IPR018114TRYPSIN_HISActive_site
IPR033116TRYPSIN_SERActive_site
IPR036943FN_type2_sfHomologous_superfamily
IPR038178Kringle_sfHomologous_superfamily
IPR043504
IPR050127Serine_Proteases_S1Family

Pfam: PF00008, PF00039, PF00040, PF00051, PF00089

Enzyme classification (BRENDA):

  • EC 3.4.21.38 — coagulation factor XIIa (BRENDA: 7 organisms, 78 substrates, 137 inhibitors, 36 Km, 35 kcat entries)

Substrate kinetics (BRENDA)

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

SubstrateKm (mM)Measurements
D-PRO-PHE-ARG-4-NITROANILIDE0.021–0.26
PREKALLIKREIN0.0008–0.00172
S-23020.1–2.72
BENZYLOXYCARBONYL-ALA-ARG-SCH2C6H50.0121
BENZYLOXYCARBONYL-ALA-ARG-SCH2CH(CH3)20.0341
BENZYLOXYCARBONYL-ALA-GLY-ARG-4-NITROANILIDE3.91
BENZYLOXYCARBONYL-ALA-PHE-ARG-4-NITROANILIDE1.51
BENZYLOXYCARBONYL-ARG-SCH2CH(CH3)20.1031
BENZYLOXYCARBONYL-ASN-GLY-ARG-4-NITROANILIDE2.71
BENZYLOXYCARBONYL-ASN-PHE-ARG-4-NITROANILIDE0.661
BENZYLOXYCARBONYL-GLU-ARG-SCH2CH(CH3)20.151
BENZYLOXYCARBONYL-GLY-ARG-SCH2CH(CH3)20.0361
BENZYLOXYCARBONYL-LYS-ARG-SCH2CH(CH3)20.0541
BENZYLOXYCARBONYL-LYS-GLY-ARG-4-NITROANILIDE0.71
BENZYLOXYCARBONYL-LYS-PHE-ARG-4-NITROANILIDE0.161

UniProt features (119 total): strand 36, disulfide bond 20, sequence variant 17, helix 12, glycosylation site 9, turn 7, domain 6, chain 3, active site 3, compositionally biased region 2, sequence conflict 2, signal peptide 1, region of interest 1

Structure

Experimental structures (PDB)

17 structures.

PDBMethodResolution (Å)
7PRJX-RAY DIFFRACTION1.2
6X0TX-RAY DIFFRACTION1.39
4BDXX-RAY DIFFRACTION1.62
7PRKX-RAY DIFFRACTION1.64
6X0SX-RAY DIFFRACTION1.9
7FBPX-RAY DIFFRACTION1.99
4XDEX-RAY DIFFRACTION2.14
6B74X-RAY DIFFRACTION2.32
6B77X-RAY DIFFRACTION2.37
4XE4X-RAY DIFFRACTION2.4
4BDWX-RAY DIFFRACTION2.5
6GT6X-RAY DIFFRACTION2.54
8R8DELECTRON MICROSCOPY2.6
6L63X-RAY DIFFRACTION3
6SZWX-RAY DIFFRACTION3.14
8OS5X-RAY DIFFRACTION3.4
6QF7X-RAY DIFFRACTION4

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P00748-F176.470.41

Antibody-complex structures (SAbDab): 1 — 8R8D

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): 412 (charge relay system); 461 (charge relay system); 563 (charge relay system)

Disulfide bonds (20): 47–73, 61–88, 98–110, 104–119, 121–130, 135–163, 161–170, 178–189, 183–198, 200–209, 217–295, 238–277, 266–290, 359–486, 397–413, 405–475, 436–439, 500–569, 532–548, 559–590

Glycosylation sites (9): 109, 249, 299, 305, 308, 328, 329, 337, 433

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

IDPathway
R-HSA-9657688Defective factor XII causes hereditary angioedema
R-HSA-9657689Defective SERPING1 causes hereditary angioedema
R-HSA-9855719Regulation of FXIIa and plasma kallikrein activity
R-HSA-9935598FXIIa, PKa-dependent activation of coagulation pathway
R-HSA-9936900Aggregated β-amyloid induces FXII autocatalysis
R-HSA-9970672FXIIa activates plasma kallikrein-kinin system
R-HSA-140837

MSigDB gene sets: 239 (showing top): MODULE_172, GOBP_POSITIVE_REGULATION_OF_PROTEIN_MATURATION, GOBP_PROTEIN_ACTIVATION_CASCADE, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_COAGULATION, GNF2_GSTM1, GNF2_HPN, GOBP_POSITIVE_REGULATION_OF_COAGULATION, GOBP_REGULATION_OF_ACUTE_INFLAMMATORY_RESPONSE, SHAFFER_IRF4_TARGETS_IN_PLASMA_CELL_VS_MATURE_B_LYMPHOCYTE, GOBP_NEGATIVE_REGULATION_OF_COAGULATION, GOBP_WOUND_HEALING, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS

GO Biological Process (15): plasma kallikrein-kinin cascade (GO:0002353), Factor XII activation (GO:0002542), blood coagulation (GO:0007596), blood coagulation, intrinsic pathway (GO:0007597), positive regulation of plasminogen activation (GO:0010756), protein processing (GO:0016485), protein autoprocessing (GO:0016540), positive regulation of blood coagulation (GO:0030194), zymogen activation (GO:0031638), fibrinolysis (GO:0042730), innate immune response (GO:0045087), response to misfolded protein (GO:0051788), positive regulation of fibrinolysis (GO:0051919), proteolysis (GO:0006508), hemostasis (GO:0007599)

GO Molecular Function (7): serine-type endopeptidase activity (GO:0004252), calcium ion binding (GO:0005509), misfolded protein binding (GO:0051787), protein binding (GO:0005515), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), rough endoplasmic reticulum (GO:0005791), plasma membrane (GO:0005886), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-4 pathways:

CategoryPathways
Defects of contact activation system and kallikrein-kinin system3
FXIIa activates plasma kallikrein-kinin system1
Regulation of clotting cascade1
Innate Immune System1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
positive regulation of protein processing2
protein processing2
negative regulation of blood coagulation2
kinin cascade1
plasma kallikrein-kinin cascade1
activation of plasma proteins involved in acute inflammatory response1
regulation of acute inflammatory response1
hemostasis1
wound healing1
coagulation1
protein activation cascade1
blood coagulation, fibrin clot formation1
regulation of plasminogen activation1
plasminogen activation1
proteolysis1
protein maturation1
blood coagulation1
regulation of blood coagulation1
positive regulation of coagulation1
positive regulation of wound healing1
positive regulation of hemostasis1
immune response1
defense response to symbiont1
response to topologically incorrect protein1
fibrinolysis1
positive regulation of biological process1
regulation of fibrinolysis1
protein metabolic process1
regulation of body fluid levels1
endopeptidase activity1
serine-type peptidase activity1
metal ion binding1
protein binding1
binding1
hydrolase activity1
catalytic activity, acting on a protein1
peptidase activity1
serine hydrolase activity1
catalytic activity1
cellular anatomical structure1

Protein interactions and networks

STRING

3751 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
F12KNG1P01042990
F12SERPING1P05155960
F12F3P13726870
F12TPPPO94811711
F12F13A1P00488701
F12KLK4Q9Y5K2669
F12SERPINF2P08697654
F12KLKB1P03952627
F12VWFP04275610
F12SERPINC1P01008591
F12ALBP02768574
F12PRDM6Q9NQX0548
F12HRGP04196517
F12PGM3O95394509
F12APOEP02649498

IntAct

19 interactions, top by confidence:

ABTypeScore
LAMP2F12psi-mi:“MI:0915”(physical association)0.560
F12APPpsi-mi:“MI:0915”(physical association)0.560
F12HSPA8psi-mi:“MI:0914”(association)0.530
F12psi-mi:“MI:0407”(direct interaction)0.440
NF12psi-mi:“MI:0407”(direct interaction)0.440
SF12psi-mi:“MI:0407”(direct interaction)0.440
KNG1F12psi-mi:“MI:0407”(direct interaction)0.440
F12KNG1psi-mi:“MI:0407”(direct interaction)0.440
F12C1QBPpsi-mi:“MI:0407”(direct interaction)0.440
LECT2psi-mi:“MI:0915”(physical association)0.400
CD5Lpsi-mi:“MI:0915”(physical association)0.400
F12psi-mi:“MI:0914”(association)0.350
F12GP1BApsi-mi:“MI:2364”(proximity)0.270

BioGRID (80): PJA1 (Affinity Capture-MS), AMBRA1 (Affinity Capture-MS), NUDCD1 (Affinity Capture-MS), KIAA0391 (Affinity Capture-MS), F12 (Co-localization), HIF1A (Affinity Capture-Western), HIF1A (Reconstituted Complex), HIF1A (Biochemical Activity), F12 (Biochemical Activity), F12 (Reconstituted Complex), F12 (Reconstituted Complex), F12 (Reconstituted Complex), F12 (Reconstituted Complex), F12 (Reconstituted Complex), ANKRD40 (Affinity Capture-MS)

ESM2 similar proteins: A1L0T3, A1L4H1, D3ZTE0, G3V801, O08762, O43866, O75636, O95428, O97507, P00748, P22457, P56730, P58215, P69525, P69526, P85521, P98140, Q02853, Q04756, Q04962, Q24K22, Q2VL90, Q2VLG4, Q2VLG6, Q2VLH6, Q499S5, Q4G0T1, Q5G265, Q5G268, Q5G269, Q5G270, Q5G271, Q5IJ48, Q6QNF4, Q70UZ7, Q769J6, Q76LX8, Q7Z410, Q80YA8, Q80YC5

Diamond homologs: A0A126GUP6, A0A1S4GMJ4, A8JUP7, B5U2W0, G3V801, O08762, O46683, O60235, O97366, O97370, P00741, P00745, P00746, P00747, P00748, P00749, P04070, P05049, P08217, P08218, P08419, P10323, P12545, P13582, P14272, P15120, P16227, P21902, P23578, P26262, P29293, P29598, P29787, P31394, P33587, P35035, P35036, P35037, P35038, P35041

SIGNOR signaling

14 interactions.

AEffectBMechanism
ESR1“up-regulates quantity by expression”F12“transcriptional regulation”
HNF4A“down-regulates quantity by repression”F12“transcriptional regulation”
F12“up-regulates activity”“GPIb-IX-V complex”binding
SERPINA1“down-regulates activity”F12binding
SERPINE1“down-regulates activity”F12binding
SERPING1“down-regulates activity”F12binding
F12“up-regulates activity”KLKB1cleavage
F12“up-regulates activity”F11cleavage
KLKB1“up-regulates activity”F12cleavage
“Blood vessel damage”up-regulatesF12
MMP13“down-regulates quantity by destabilization”F12cleavage
MMP14“down-regulates quantity by destabilization”F12cleavage
MMP12“down-regulates quantity by destabilization”F12cleavage
SERPINC1“down-regulates activity”F12cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic8
Likely pathogenic9
Uncertain significance116
Likely benign51
Benign18

Top pathogenic / likely-pathogenic (17)

Variant IDHGVSClassification
1164NM_000505.4(F12):c.1768T>A (p.Cys590Ser)Pathogenic
1169NM_000505.4(F12):c.983C>A (p.Thr328Lys)Pathogenic
1170NM_000505.4(F12):c.983C>G (p.Thr328Arg)Pathogenic
3066136NM_000505.4(F12):c.1570del (p.Val524fs)Pathogenic
3381898NM_000505.4(F12):c.303_304del (p.His101fs)Pathogenic
403709NM_000505.4(F12):c.894_911dup (p.Gln300_Thr305dup)Pathogenic
4085814NM_000505.4(F12):c.800+2T>CPathogenic
4770174NM_000505.4(F12):c.1532-1G>APathogenic
1473234NM_000505.4(F12):c.800+1G>ALikely pathogenic
2572132NM_000505.4(F12):c.1517del (p.Gly506fs)Likely pathogenic
2671919NM_000505.4(F12):c.415C>T (p.Gln139Ter)Likely pathogenic
3381899NM_000505.4(F12):c.1561G>A (p.Glu521Lys)Likely pathogenic
3779632NM_000505.4(F12):c.1375C>T (p.Gln459Ter)Likely pathogenic
3779633NM_000505.4(F12):c.1681-1G>CLikely pathogenic
4081386NM_000505.4(F12):c.800+1G>CLikely pathogenic
4086125NM_000505.4(F12):c.312C>A (p.Cys104Ter)Likely pathogenic
4849475NM_000505.4(F12):c.1158C>A (p.Tyr386Ter)Likely pathogenic

SpliceAI

1817 predictions. Top by Δscore:

VariantEffectΔscore
5:177402699:C:CCacceptor_gain1.0000
5:177403252:AC:Adonor_gain1.0000
5:177403253:CC:Cdonor_gain1.0000
5:177403477:GCA:Gdonor_loss1.0000
5:177403478:CA:Cdonor_loss1.0000
5:177403479:AC:Adonor_gain1.0000
5:177403479:ACCCA:Adonor_loss1.0000
5:177403480:C:Tdonor_loss1.0000
5:177403480:CC:Cdonor_gain1.0000
5:177403497:G:Cdonor_gain1.0000
5:177403613:CGGGC:Cacceptor_gain1.0000
5:177403616:GCCT:Gacceptor_loss1.0000
5:177403618:C:CCacceptor_gain1.0000
5:177403619:T:Gacceptor_loss1.0000
5:177403715:T:TAdonor_gain1.0000
5:177404189:T:TAdonor_gain1.0000
5:177404352:C:CAdonor_gain1.0000
5:177404915:C:CCacceptor_gain1.0000
5:177404916:T:Cacceptor_gain1.0000
5:177404916:T:TCacceptor_gain1.0000
5:177405317:CCTCA:Cdonor_loss1.0000
5:177405318:CTCAC:Cdonor_loss1.0000
5:177405319:TCAC:Tdonor_loss1.0000
5:177405320:CACCT:Cdonor_loss1.0000
5:177405322:C:CGdonor_loss1.0000
5:177405322:CCTTT:Cdonor_gain1.0000
5:177405430:TGGT:Tacceptor_gain1.0000
5:177405434:C:CAacceptor_loss1.0000
5:177405434:C:CCacceptor_gain1.0000
5:177405441:A:ACacceptor_gain1.0000

AlphaMissense

3972 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
5:177403270:C:AW505C0.996
5:177403270:C:GW505C0.996
5:177402316:C:AW608C0.994
5:177402316:C:GW608C0.994
5:177403909:G:CS400R0.994
5:177403909:G:TS400R0.994
5:177403911:T:GS400R0.994
5:177402385:G:CS585R0.992
5:177402385:G:TS585R0.992
5:177402387:T:GS585R0.992
5:177402587:C:GC548S0.991
5:177402588:A:TC548S0.991
5:177403486:T:AD461V0.991
5:177404576:C:AW241C0.991
5:177404576:C:GW241C0.991
5:177402371:C:GC590S0.990
5:177402372:A:TC590S0.990
5:177403509:G:CF453L0.990
5:177403509:G:TF453L0.990
5:177403511:A:GF453L0.990
5:177402382:C:AW586C0.989
5:177402382:C:GW586C0.989
5:177402554:C:GC559S0.989
5:177402555:A:TC559S0.989
5:177404386:C:AW276C0.989
5:177404386:C:GW276C0.989
5:177403272:A:GW505R0.988
5:177403272:A:TW505R0.988
5:177403486:T:GD461A0.988
5:177403946:G:TA388D0.988

dbSNP variants (sampled 300 via entrez): RS1000017177 (5:177407982 A>G), RS1000152826 (5:177408418 G>C), RS1000253382 (5:177402599 G>A), RS1000724019 (5:177402813 C>A,G), RS1002351228 (5:177410339 A>C,G,T), RS1003022805 (5:177404260 C>A,G,T), RS1003030115 (5:177410722 G>A,C), RS1003774012 (5:177405605 C>G,T), RS1003881489 (5:177409321 C>T), RS1003936722 (5:177403378 C>A), RS1004033829 (5:177409247 T>G), RS1004055643 (5:177402925 A>C), RS1005892191 (5:177406295 T>C), RS1006380773 (5:177407742 G>A), RS1006390819 (5:177407510 C>A,T)

Disease associations

OMIM: gene MIM:610619 | disease phenotypes: MIM:234000, MIM:610618, MIM:106100

GenCC curated gene-disease

DiseaseClassificationInheritance
hereditary angioedema type 3DefinitiveAutosomal dominant
congenital factor XII deficiencyStrongAutosomal recessive

ClinGen Gene-Disease Validity (2)

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

DiseaseClassificationInheritance
congenital factor XII deficiencyDefinitiveAR
hereditary angioedema type 3DefinitiveAD

Mondo (7): congenital factor XII deficiency (MONDO:0009315), hereditary angioedema type 3 (MONDO:0012526), hereditary angioedema (MONDO:0019623), hypertensive disorder (MONDO:0005044), urticaria (MONDO:0005492), angioedema (MONDO:0010481), hyperbilirubinemia (MONDO:0024288)

Orphanet (3): F12-related hereditary angioedema with normal C1Inh (Orphanet:100054), Congenital factor XII deficiency (Orphanet:330), Hereditary angioedema (Orphanet:91378)

HPO phenotypes

19 total (21 of 19 shown, HPO-id order):

HPOTerm
HP:0000006Autosomal dominant inheritance
HP:0000007Autosomal recessive inheritance
HP:0000282Facial edema
HP:0001026Penetrating foot ulcers
HP:0001892Abnormal bleeding
HP:0001907Thromboembolism
HP:0001977Abnormal thrombosis
HP:0002013Vomiting
HP:0002574Episodic abdominal pain
HP:0003645Prolonged partial thromboplastin time
HP:0004841Reduced factor XII activity
HP:0005225Intestinal edema
HP:0005542Prolonged whole-blood clotting time
HP:0007985Retinal arteriolar occlusion
HP:0011855Pharyngeal edema
HP:0012271Episodic upper airway obstruction
HP:0012636Retinal venous occlusion
HP:0100665Angioedema
HP:0200067Recurrent spontaneous abortion
HP:0000822Hypertension
HP:0001025Urticaria

GWAS associations

24 associations (top):

StudyTraitp-value
GCST000631_1Activated partial thromboplastin time2.000000e-30
GCST000649_23Chronic kidney disease1.000000e-14
GCST001065_1Platelet function and related traits1.000000e-06
GCST001391_3Metabolite levels9.000000e-11
GCST001432_1Nephrolithiasis9.000000e-12
GCST001574_7Activated partial thromboplastin time6.000000e-88
GCST001639_21Metabolite levels3.000000e-14
GCST001853_4Circulating vasoactive peptide levels6.000000e-24
GCST001853_5Circulating vasoactive peptide levels1.000000e-67
GCST003793_2L-arginine levels1.000000e-12
GCST004038_3Circulating chromogranin peptide levels2.000000e-19
GCST005956_15Waist-to-hip ratio adjusted for BMI1.000000e-07
GCST005957_13Waist-to-hip ratio adjusted for BMI (age <50)3.000000e-07
GCST005962_42Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)1.000000e-08
GCST006018_9Activated partial thromboplastin time0.000000e+00
GCST007638_34Glycine levels7.000000e-14
GCST008309_12Cardiac troponin-I levels2.000000e-07
GCST011541_5Tinnitus2.000000e-07
GCST012020_560Serum metabolite levels2.000000e-22
GCST012020_561Serum metabolite levels2.000000e-45
GCST012020_562Serum metabolite levels5.000000e-35
GCST012021_10Serum metabolite levels5.000000e-35
GCST012021_8Serum metabolite levels2.000000e-22
GCST012021_9Serum metabolite levels2.000000e-45

EFO canonical traits (10, from GWAS)

EFO IDTrait name
EFO:0004725metabolite measurement
EFO:0004723coronary artery calcification
EFO:0005196vasoactive peptide measurement
EFO:0006524L-arginine measurement
EFO:0007909CHGA cleavage product measurement
EFO:0007788BMI-adjusted waist-hip ratio
EFO:0008007age at assessment
EFO:0008343sex interaction measurement
EFO:0009767glycine measurement
EFO:0010071cardiac troponin I measurement

MeSH disease descriptors (7)

DescriptorNameTree numbers
D000799AngioedemaC14.907.079; C17.800.862.945.066; C20.543.480.904.066
D054179Angioedemas, HereditaryC14.907.079.500; C16.320.798.500.500; C17.800.862.945.066.500; C20.543.480.904.066.500; C20.673.795.500.500
D005175Factor XII DeficiencyC15.378.100.100.330; C15.378.100.141.330; C15.378.463.330; C16.320.099.330
D056828Hereditary Angioedema Type IIIC14.907.079.500.500; C17.800.862.945.066.500.500; C20.543.480.904.066.500.500
D006932HyperbilirubinemiaC23.550.429
D006973HypertensionC14.907.489
D014581UrticariaC17.800.862.945; C20.543.480.904

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2821 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 9,250 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL273264NAFAMOSTAT37,063
CHEMBL87563GABEXATE32,031
CHEMBL114586SEPIMOSTAT2156

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

PharmGKB clinical annotations

1 annotations.

VariantTypeLevelDrugsPhenotypes
rs1801020Efficacy3EnzymesStroke

PharmGKB variants

1 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs1801020F12, SLC34A133.501Enzymes

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — S1: Chymotrypsin

Most potent curated ligand interactions (3 total), top 3:

LigandActionAffinityParameter
garadacimabBinding9.82pKd
anti-FXII nanobody N4-38Binding8.51pKd
methyl 5-[(4-tert-butylbenzoyl)amino]-2H-1,2,4-triazole-3-carboxylateInhibition8.0pIC50

Binding affinities (BindingDB)

200 measured of 1015 human assays (1021 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
(2S)-N-[(3-chloro-1H-indol-5- yl)methyl]-1-[N-(1-methylethyl)-6- piperidin-1-yl-D-norleucyl]-4- [(4S,5S)-4-methyl-5-phenyl-4,5- dihydro-1,3-oxazol-2-yl]piperazine-2- carboxamideIC500.5 nMUS-10875851: Factor XIIa inhibitors
(2S)-1-{N-[4- (aminomethyl)cyclohexyl]-6- piperidin-1-yl-D-norleucyl}-N-[(3- chloro-1H-indol-5-yl)methyl]-4- [(4S,5S)-4-methyl-5-phenyl-4,5- dihydro-1,3-oxazol-2-yl]piperazine-2- carboxamideIC500.6 nMUS-10875851: Factor XIIa inhibitors
(2S)-N-[(3-chloro-1H-indol-5- yl)methyl]-4-(4,4-dimethyl-5-phenyl- 4,5-dihydro-1,3-oxazol-2-yl)-1- (N2,N2,N6,N6-tetramethyl-D- lysyl)piperazine-2-carboxamideIC506.7 nMUS-10875851: Factor XIIa inhibitors
(2S)-N-[(3-chloro-1H-indol-5- yl)methyl]-4-[(4S,5S)-4-methyl-5- phenyl-4,5-dihydro-1,3-oxazol-2-yl]- 1-(6-piperidin-1-yl-D- norleucyl)piperazine-2-carboxamideIC508.4 nMUS-10875851: Factor XIIa inhibitors
3-[(4-tert-butylbenzoyl)amino]-1H-1,2,4-triazole-5-carboxylic acid methyl esterIC5010.4 nM
2-chlorophenyl (3S)-4-{2(R)-2- (cyclohexylamino)-2-[1-(1H-pyrazol- 4-ylsulfonyl)piperidin-4-yl]acetyl}-3- [(thiophen-2- ylmethyl)carbamoyl]piperzine-1- carboxylateIC5021.1 nMUS-10875851: Factor XIIa inhibitors
MLS000708242IC5023.6 nM
TATA-FXII618 (14)KI25 nM
3-[(4-fluorobenzoyl)amino]-1H-1,2,4-triazole-5-carboxylic acid methyl esterIC5029.6 nM
(S*)-(3-amino-6- (methylsulfonyl)- 4,5,6,7- tetrahydro- pyrazolo[3,4- c]pyridin-2- yl)(2-chloro- 4,5,6,7-IC5030 nMUS-11312723: Pyranopyrazole and pyrazolopyridine immunomodulators for treatment of autoimmune diseases
1-benzoyl-3-(4-methoxyphenyl)-1H-1,2,4-triazol-5-amineIC5044 nM
6-chloro-2-methoxyacridin-9-amineKI49 nM
(6-methyl-3-nitro-2-oxidanylidene-1H-pyridin-4-yl) (E)-3-(3,4-dimethoxyphenyl)prop-2-enoateIC5049.5 nM
3-[(2-bromobenzoyl)amino]-1H-1,2,4-triazole-5-carboxylic acid methyl esterIC5072 nM
(5-amino-3-pyridin-3-yl-1,2,4-triazol-1-yl)-(4-fluorophenyl)methanoneIC5080.8 nM
(5-amino-3-pyridin-3-yl-1,2,4-triazol-1-yl)-(2-chlorophenyl)methanoneIC5089.9 nM
3-benzamido-1H-1,2,4-triazole-5-carboxylic acid methyl esterIC5092.4 nM
MLS000706208IC50159 nM
2,3,5,6-tetrachlorocyclohexa-2,5-diene-1,4-dioneKI163 nM
5-amino-1-(4-methoxybenzoyl)pyrazole-4-carbonitrileIC50195 nM
MLS000708241IC50237 nM
MLS000708243IC50238 nM
2-(2-chlorophenyl)-4-thieno[3,2-d][1,3]oxazinoneIC50241 nM
(3-amino-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-2-yl)-(2-ethyl-4,5,6,7-tetrahydro-1H-indol-4-yl)methanoneIC50250 nMUS-11312723: Pyranopyrazole and pyrazolopyridine immunomodulators for treatment of autoimmune diseases
Benzyl 3-amino-2-(2-ethyl-4,5,6,7-tetrahydro-1H-indole-4-carbonyl)-6,7-dihydro-2H-pyrazolo[4,3-c]pyridine-5(4H)-carboxylate and benzyl 3-amino-1-(2-ethyl-4,5,6,7-tetrahydro-1H-indole-4-carbonyl)-6,7-dihydro-1H-pyrazolo[4,3-c]pyridine-5(4H)-carboxylateIC50300 nMUS-11312723: Pyranopyrazole and pyrazolopyridine immunomodulators for treatment of autoimmune diseases
(5-amino-3-pyridin-3-yl-1,2,4-triazol-1-yl)-(4-chlorophenyl)methanoneIC50327 nM
TATB-FXII618 (15)KI340 nM
(3-amino-5-methyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-2-yl)-(2-chloro-4,5,6,7-tetrahydro-1H-indol-4-yl)methanoneIC50350 nMUS-11312723: Pyranopyrazole and pyrazolopyridine immunomodulators for treatment of autoimmune diseases
(3-Amino-[1,2,4]triazol-4-yl)-(3,5-dimethoxy-phenyl)-methanoneIC50376 nM
(2R)-2-(benzylsulfonylamino)-N-[(2S)-1-[(4-carbamimidoylphenyl)methylamino]-1-oxo-4-piperidin-4-ylbutan-2-yl]-5-(1-oxidopyridin-1-ium-4-yl)pentanamideKI400 nMUS-8598206: Trypsin-like serine protease inhibitors, and their preparation and use
methyl 4-[(4R)-4-(benzylsulfonylamino)-5-[[(2S)-1-[(4-carbamimidoylphenyl)methylamino]-1-oxo-4-piperidin-4-ylbutan-2-yl]amino]-5-oxopentyl]piperidine-1-carboxylateKI400 nMUS-8598206: Trypsin-like serine protease inhibitors, and their preparation and use
MLS000419584IC50455 nM
7-ethoxyacridine-3,9-diamineKI490 nM
(4-methyl-5-thioxo-1,2,4-triazol-1-yl)-(p-tolyl)methanoneIC50498 nM
(3-amino-1,2,4-triazol-4-yl)-(3-methylphenyl)methanoneIC50500 nM
(5-amino-3-pyridin-3-yl-1,2,4-triazol-1-yl)-(2-methoxyphenyl)methanoneIC50503 nM
2,6-dimethylbenzo-1,4-quinone 4-[O-(3,4,5-trimethoxybenzoyl)oxime]IC50533 nM
4-(4-methoxybenzoyloxyimino)-2,6-dimethylcyclohexa-2,5-dienoneIC50574 nM
MLS000672621IC50595 nM
2-methylbenzo-1,4-quinone 4-[O-(3,4,5-trimethoxybenzoyl)oxime]IC50623 nM
(5-Amino-3-furan-2-yl-[1,2,4]triazol-1-yl)-phenyl-methanoneIC50643 nM
MLS000679754IC50650 nM
1-benzotriazolyl-(1-phenyl-3-pyridin-4-yl-4-pyrazolyl)methanoneIC50707 nM
BDBM108100KI750 nMUS-8598206: Trypsin-like serine protease inhibitors, and their preparation and use
1-benzotriazolyl-(3,4-dimethoxyphenyl)methanoneIC50755 nM
(2R)-2-(benzylsulfonylamino)-N-[(2S)-1-[(4-carbamimidoylphenyl)methylamino]-1-oxo-4-piperidin-4-ylbutan-2-yl]-5-pyridin-4-ylpentanamideKI850 nMUS-8598206: Trypsin-like serine protease inhibitors, and their preparation and use
2-nitro-9,10-dihydrophenanthrene-9,10-dioneKI850 nM
5,6-dinitro-1,2-dihydroacenaphthylenedioneKI903 nM
MLS000097371IC50923 nM
2-furancarboxylic acid [5-amino-1-(4-methoxyphenyl)sulfonyl-3-pyrazolyl] esterIC50924 nM

ChEMBL bioactivities

612 potent at pChembl≥5 of 729 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
10.00IC500.1nMCHEMBL5758818
9.70IC500.2nMCHEMBL6054063
9.52IC500.3nMCHEMBL6043307
9.52IC500.3nMCHEMBL5805584
9.40IC500.4nMCHEMBL5923412
9.30IC500.5nMCHEMBL5777358
9.30IC500.5nMCHEMBL6046462
9.30IC500.5nMCHEMBL5864799
9.22IC500.6nMCHEMBL5895805
9.15IC500.7nMCHEMBL5857165
9.15IC500.7nMCHEMBL5868011
9.15IC500.7nMCHEMBL5850559
9.10IC500.8nMCHEMBL5923412
9.08Ki0.84nMCHEMBL4088217
9.05Ki0.89nMCHEMBL4098389
9.05IC500.9nMCHEMBL5857165
9.05IC500.9nMCHEMBL5959689
9.00IC501nMCHEMBL5903837
9.00IC501nMCHEMBL6042515
8.96IC501.1nMCHEMBL5856084
8.96IC501.1nMCHEMBL5878932
8.96IC501.1nMCHEMBL5740724
8.92IC501.2nMCHEMBL5865847
8.85IC501.4nMCHEMBL5980829
8.85IC501.4nMCHEMBL5957724
8.82IC501.5nMCHEMBL5772996
8.82IC501.5nMCHEMBL6014897
8.80IC501.6nMCHEMBL5994109
8.79Ki1.64nMCHEMBL4059973
8.79Ki1.63nMCHEMBL4087027
8.77IC501.7nMCHEMBL5874485
8.77IC501.7nMCHEMBL5890124
8.77IC501.7nMCHEMBL6053959
8.74IC501.8nMCHEMBL6032652
8.74IC501.8nMCHEMBL5865847
8.68IC502.1nMCHEMBL5969008
8.62IC502.4nMCHEMBL5782144
8.60IC502.5nMCHEMBL6044778
8.59IC502.6nMCHEMBL5799619
8.57IC502.7nMCHEMBL5961528
8.54IC502.9nMCHEMBL6057827
8.52Ki3nMCHEMBL4102962
8.52IC503nMCHEMBL6015163
8.48IC503.3nMCHEMBL5954361
8.47IC503.4nMCHEMBL5871675
8.43Ki3.7nMCHEMBL4065450
8.43IC503.7nMCHEMBL5874818
8.42IC503.8nMCHEMBL5787807
8.41IC503.9nMCHEMBL6006497
8.41IC503.9nMCHEMBL5825188

PubChem BioAssay actives

347 with measured affinity, of 877 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.

CompoundAssayTypeValueUnit
(2S)-2-[[(9R,12S,15S,18S,24S,27R,30S,33S,36S,39S,42R)-9-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-33-(3-amino-3-oxopropyl)-15,30,39-tris(3-carbamimidamidopropyl)-12-[(4-fluorophenyl)methyl]-18,36-bis(2-methylpropyl)-4,10,13,16,19,25,28,31,34,37,40,47,50-tridecaoxo-7,44,53-trithia-1,3,11,14,17,20,26,29,32,35,38,41,48-tridecazatetracyclo[25.22.5.13,48.020,24]pentapentacontane-42-carbonyl]amino]-5-carbamimidamidopentanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0008uM
(2S)-2-[[(2S)-2-[[(9R,12S,15S,18S,24S,27R,30S,33S,36S,39S,42R)-9-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-33-(3-amino-3-oxopropyl)-15,30,39-tris(3-carbamimidamidopropyl)-12-[(4-fluorophenyl)methyl]-18,36-bis(2-methylpropyl)-4,10,13,16,19,25,28,31,34,37,40,47,50-tridecaoxo-7,44,53-trithia-1,3,11,14,17,20,26,29,32,35,38,41,48-tridecazatetracyclo[25.22.5.13,48.020,24]pentapentacontane-42-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0009uM
(2S)-2-[[(2S)-2-[[(9R,12S,15S,18S,24S,27R,30S,33S,36S,39S,42R)-9-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-33-(3-amino-3-oxopropyl)-15,30,39-tris(3-carbamimidamidopropyl)-18,36-bis(2-methylpropyl)-12-[(4-nitrophenyl)methyl]-4,10,13,16,19,25,28,31,34,37,40,47,50-tridecaoxo-7,44,53-trithia-1,3,11,14,17,20,26,29,32,35,38,41,48-tridecazatetracyclo[25.22.5.13,48.020,24]pentapentacontane-42-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0016uM
(2S)-2-[[(9R,12S,15S,18S,24S,27R,30S,33S,36S,39S,42R)-9-[[(2S)-2-amino-4-carbamimidamidobutanoyl]amino]-33-(3-amino-3-oxopropyl)-15,30,39-tris(3-carbamimidamidopropyl)-12-[(4-fluorophenyl)methyl]-18,36-bis(2-methylpropyl)-4,10,13,16,19,25,28,31,34,37,40,47,50-tridecaoxo-7,44,53-trithia-1,3,11,14,17,20,26,29,32,35,38,41,48-tridecazatetracyclo[25.22.5.13,48.020,24]pentapentacontane-42-carbonyl]amino]-5-carbamimidamidopentanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0016uM
(2S)-2-[[(2S)-2-[[(9R,12S,15S,18S,24S,27R,30S,33S,36S,39S,42R)-9-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-33-(3-amino-3-oxopropyl)-15,30,39-tris(3-carbamimidamidopropyl)-18,36-bis(2-methylpropyl)-4,10,13,16,19,25,28,31,34,37,40,47,50-tridecaoxo-12-(pyridin-3-ylmethyl)-7,44,53-trithia-1,3,11,14,17,20,26,29,32,35,38,41,48-tridecazatetracyclo[25.22.5.13,48.020,24]pentapentacontane-42-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0030uM
(2S)-2-[[(2S)-2-[[(9R,12S,15S,18S,24S,27R,30S,33S,36S,39S,42R)-9-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-33-(3-amino-3-oxopropyl)-15,30,39-tris(3-carbamimidamidopropyl)-12-[(3-methylphenyl)methyl]-18,36-bis(2-methylpropyl)-4,10,13,16,19,25,28,31,34,37,40,47,50-tridecaoxo-7,44,53-trithia-1,3,11,14,17,20,26,29,32,35,38,41,48-tridecazatetracyclo[25.22.5.13,48.020,24]pentapentacontane-42-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0037uM
1-(3,4-dimethylphenyl)-2-phenylethane-1,2-dione1798224: Enzyme Inhibition Assay from Article 10.1021/jm049011j: “Identification and characterization of novel benzil (diphenylethane-1,2-dione) analogues as inhibitors of mammalian carboxylesterases.”ki0.0041uM
(2S)-2-[[(2S)-2-[[(9R,12S,15S,18S,24S,27R,30S,33S,36S,39S,42R)-9-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-33-(3-amino-3-oxopropyl)-15,30,39-tris(3-carbamimidamidopropyl)-12-[(3-fluorophenyl)methyl]-18,36-bis(2-methylpropyl)-4,10,13,16,19,25,28,31,34,37,40,47,50-tridecaoxo-7,44,53-trithia-1,3,11,14,17,20,26,29,32,35,38,41,48-tridecazatetracyclo[25.22.5.13,48.020,24]pentapentacontane-42-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0045uM
1,2-dicyclohexylethane-1,2-dione1798260: Enzyme Inhibition Assay from Article 10.1021/jm0706867: “Planarity and constraint of the carbonyl groups in 1,2-diones are determinants for selective inhibition of human carboxylesterase 1.”ki0.0050uM
1-[4-(2-oxo-2-phenylacetyl)phenyl]-2-phenylethane-1,2-dione1798224: Enzyme Inhibition Assay from Article 10.1021/jm049011j: “Identification and characterization of novel benzil (diphenylethane-1,2-dione) analogues as inhibitors of mammalian carboxylesterases.”ki0.0056uM
(2S)-2-[[(2S)-2-[[(9R,12S,15S,18S,24S,27R,30S,33S,36S,39S,42R)-9-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-33-(3-amino-3-oxopropyl)-15,30,39-tris(3-carbamimidamidopropyl)-18,36-bis(2-methylpropyl)-12-(naphthalen-2-ylmethyl)-4,10,13,16,19,25,28,31,34,37,40,47,50-tridecaoxo-7,44,53-trithia-1,3,11,14,17,20,26,29,32,35,38,41,48-tridecazatetracyclo[25.22.5.13,48.020,24]pentapentacontane-42-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0060uM
(2S)-2-[[(9R,12S,15S,18S,24S,27R,30S,33S,36S,39S,42R)-33-(3-amino-3-oxopropyl)-12-benzyl-15,30,39-tris(3-carbamimidamidopropyl)-9-[[(2R)-2,7-diaminoheptanoyl]amino]-18,36-bis(2-methylpropyl)-4,10,13,16,19,25,28,31,34,37,40,47,50-tridecaoxo-7,44,53-trithia-1,3,11,14,17,20,26,29,32,35,38,41,48-tridecazatetracyclo[25.22.5.13,48.020,24]pentapentacontane-42-carbonyl]amino]-5-carbamimidamidopentanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0065uM
(2S)-2-[[(2S)-2-[[(9R,12S,15S,18S,24S,27R,30S,33S,36S,39S,42R)-9-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-33-(3-amino-3-oxopropyl)-12-(1-benzothiophen-3-ylmethyl)-15,30,39-tris(3-carbamimidamidopropyl)-18,36-bis(2-methylpropyl)-4,10,13,16,19,25,28,31,34,37,40,47,50-tridecaoxo-7,44,53-trithia-1,3,11,14,17,20,26,29,32,35,38,41,48-tridecazatetracyclo[25.22.5.13,48.020,24]pentapentacontane-42-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0068uM
aceanthrylene-1,2-dione1798260: Enzyme Inhibition Assay from Article 10.1021/jm0706867: “Planarity and constraint of the carbonyl groups in 1,2-diones are determinants for selective inhibition of human carboxylesterase 1.”ki0.0077uM
1-(4-methyl-3-nitrophenyl)-2-phenylethane-1,2-dione1798224: Enzyme Inhibition Assay from Article 10.1021/jm049011j: “Identification and characterization of novel benzil (diphenylethane-1,2-dione) analogues as inhibitors of mammalian carboxylesterases.”ki0.0079uM
1-dodecylindole-2,3-dione1798240: Enzyme Inhibition Assay from Article 10.1021/jm061471k: “Selective inhibition of carboxylesterases by isatins, indole-2,3-diones.”ki0.0080uM
(2S)-2-[[(9R,12S,15S,18S,24S,27R,30S,33S,36S,39S,42R)-9-[[(2R)-2-amino-6-carbamimidamidohexanoyl]amino]-33-(3-amino-3-oxopropyl)-12-benzyl-15,30,39-tris(3-carbamimidamidopropyl)-18,36-bis(2-methylpropyl)-4,10,13,16,19,25,28,31,34,37,40,47,50-tridecaoxo-7,44,53-trithia-1,3,11,14,17,20,26,29,32,35,38,41,48-tridecazatetracyclo[25.22.5.13,48.020,24]pentapentacontane-42-carbonyl]amino]-5-carbamimidamidopentanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0088uM
1-(2-chlorophenyl)-2-(3,4-dimethoxyphenyl)ethane-1,2-dione1798224: Enzyme Inhibition Assay from Article 10.1021/jm049011j: “Identification and characterization of novel benzil (diphenylethane-1,2-dione) analogues as inhibitors of mammalian carboxylesterases.”ki0.0089uM
(2S)-2-[[(9R,12S,15S,18S,24S,27R,30S,33S,36S,39S,42R)-33-(3-amino-3-oxopropyl)-12-benzyl-15,30,39-tris(3-carbamimidamidopropyl)-9-[[(2S)-2,6-diaminohexanoyl]amino]-18,36-bis(2-methylpropyl)-4,10,13,16,19,25,28,31,34,37,40,47,50-tridecaoxo-7,44,53-trithia-1,3,11,14,17,20,26,29,32,35,38,41,48-tridecazatetracyclo[25.22.5.13,48.020,24]pentapentacontane-42-carbonyl]amino]-5-carbamimidamidopentanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0090uM
(9R,12S,15S,18S,24S,27R,30S,33S,36S,39S,42R)-9-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-33-(3-amino-3-oxopropyl)-12-benzyl-15,30,39-tris[3-(diaminomethylideneamino)propyl]-18,36-bis(2-methylpropyl)-4,10,13,16,19,25,28,31,34,37,40,47,50-tridecaoxo-7,44,53-trithia-1,3,11,14,17,20,26,29,32,35,38,41,48-tridecazatetracyclo[25.22.5.13,48.020,24]pentapentacontane-42-carboxylic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0093uM
(2S)-2-[[(2S)-2-[[(9R,12S,15S,18S,24S,27R,30S,33S,36S,39S,42R)-9-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-33-(3-amino-3-oxopropyl)-15,30,39-tris(3-carbamimidamidopropyl)-18,36-bis(2-methylpropyl)-12-(naphthalen-1-ylmethyl)-4,10,13,16,19,25,28,31,34,37,40,47,50-tridecaoxo-7,44,53-trithia-1,3,11,14,17,20,26,29,32,35,38,41,48-tridecazatetracyclo[25.22.5.13,48.020,24]pentapentacontane-42-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0100uM
5-N-[[4-methyl-6-[(8S)-8-methyl-3-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-3-pyridinyl]methyl]isoquinoline-1,5-diamine2066075: Inhibition of human FXIIa (unknown origin)ic500.0100uM
1-[[4-[[4-[(2,3-dioxoindol-1-yl)methyl]phenyl]methyl]phenyl]methyl]indole-2,3-dione1798240: Enzyme Inhibition Assay from Article 10.1021/jm061471k: “Selective inhibition of carboxylesterases by isatins, indole-2,3-diones.”ki0.0100uM
(2S)-2-[[(2S)-2-[[(9R,12S,15S,18S,24S,27R,30S,33S,36S,39S,42R)-9-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-33-(3-amino-3-oxopropyl)-12-benzyl-15,30,39-tris(3-carbamimidamidopropyl)-18,36-bis(2-methylpropyl)-4,10,13,16,19,25,28,31,34,37,40,47,50-tridecaoxo-7,44,53-trithia-1,3,11,14,17,20,26,29,32,35,38,41,48-tridecazatetracyclo[25.22.5.13,48.020,24]pentapentacontane-42-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0102uM
1-(4-methoxyphenyl)-2-phenylethane-1,2-dione1798224: Enzyme Inhibition Assay from Article 10.1021/jm049011j: “Identification and characterization of novel benzil (diphenylethane-1,2-dione) analogues as inhibitors of mammalian carboxylesterases.”ki0.0103uM
1-hexadecylindole-2,3-dione1798240: Enzyme Inhibition Assay from Article 10.1021/jm061471k: “Selective inhibition of carboxylesterases by isatins, indole-2,3-diones.”ki0.0110uM
(5-amino-3-pyridin-2-yl-1,2,4-triazol-1-yl)-[4-(4-propan-2-yl-1,4-diazepan-1-yl)naphthalen-1-yl]methanone2066015: Binding affinity to FXIIa (unknown origin) assessed as inhibition constant using H-D-Pro-Phe-Arg-pNA.2HCl as substrate by spectrophotometric analysiski0.0114uM
(2S)-2-[[(2S)-2-[[(9R,12S,15S,18S,24S,27R,30S,33S,36S,39S,42R)-9-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-33-(3-amino-3-oxopropyl)-15,30,39-tris(3-carbamimidamidopropyl)-12-(1H-indol-3-ylmethyl)-18,36-bis(2-methylpropyl)-4,10,13,16,19,25,28,31,34,37,40,47,50-tridecaoxo-7,44,53-trithia-1,3,11,14,17,20,26,29,32,35,38,41,48-tridecazatetracyclo[25.22.5.13,48.020,24]pentapentacontane-42-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0120uM
(2S)-2-[[(2S)-2-[[(9R,12S,15S,18S,21S,24R,27S,30S,33S,36S,39R)-39-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-18-(3-amino-3-oxopropyl)-36-benzyl-12,21,33-tris(3-carbamimidamidopropyl)-15,27,30-tris(2-methylpropyl)-4,11,14,17,20,23,26,29,32,35,38,44,47-tridecaoxo-7,41,50-trithia-1,3,10,13,16,19,22,25,28,31,34,37,45-tridecazatricyclo[22.22.5.13,45]dopentacontane-9-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0130uM
(2S)-2-[[(9R,12S,15S,18S,24S,27R,30S,33S,36S,39S,42R)-9-[[(2R)-2-amino-4-carbamimidamidobutanoyl]amino]-33-(3-amino-3-oxopropyl)-12-benzyl-15,30,39-tris(3-carbamimidamidopropyl)-18,36-bis(2-methylpropyl)-4,10,13,16,19,25,28,31,34,37,40,47,50-tridecaoxo-7,44,53-trithia-1,3,11,14,17,20,26,29,32,35,38,41,48-tridecazatetracyclo[25.22.5.13,48.020,24]pentapentacontane-42-carbonyl]amino]-5-carbamimidamidopentanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0140uM
1,2-diphenylethane-1,2-dione1798224: Enzyme Inhibition Assay from Article 10.1021/jm049011j: “Identification and characterization of novel benzil (diphenylethane-1,2-dione) analogues as inhibitors of mammalian carboxylesterases.”ki0.0147uM
(2S)-2-[[(9R,12S,15S,18S,24S,27R,30S,33S,36S,39S,42R)-9-[[(2R)-2-amino-3-(4-carbamimidamidophenyl)propanoyl]amino]-33-(3-amino-3-oxopropyl)-12-benzyl-15,30,39-tris(3-carbamimidamidopropyl)-18,36-bis(2-methylpropyl)-4,10,13,16,19,25,28,31,34,37,40,47,50-tridecaoxo-7,44,53-trithia-1,3,11,14,17,20,26,29,32,35,38,41,48-tridecazatetracyclo[25.22.5.13,48.020,24]pentapentacontane-42-carbonyl]amino]-5-carbamimidamidopentanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0150uM
(2S)-1-[(2R)-3-cyclohexyl-2-(cyclohexylamino)propanoyl]-4-[(4R,5S)-4-methyl-5-phenyl-4,5-dihydro-1,3-oxazol-2-yl]-N-(thiophen-2-ylmethyl)piperazine-2-carboxamide2066075: Inhibition of human FXIIa (unknown origin)ic500.0171uM
(2S)-2-[[(2S)-2-[[(9R,12S,15S,18S,24S,27R,30S,33S,36S,39S,42R)-9-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-33-(3-amino-3-oxopropyl)-12-benzyl-15,30,39-tris(3-carbamimidamidopropyl)-36-(2,2-dimethylpropyl)-18-(2-methylpropyl)-4,10,13,16,19,25,28,31,34,37,40,47,50-tridecaoxo-7,44,53-trithia-1,3,11,14,17,20,26,29,32,35,38,41,48-tridecazatetracyclo[25.22.5.13,48.020,24]pentapentacontane-42-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0177uM
1-(4-chlorophenyl)-2-phenylethane-1,2-dione1798224: Enzyme Inhibition Assay from Article 10.1021/jm049011j: “Identification and characterization of novel benzil (diphenylethane-1,2-dione) analogues as inhibitors of mammalian carboxylesterases.”ki0.0182uM
(2S)-2-[[(2S)-2-[[(9R,12S,15S,18S,21S,24R,27S,30S,33S,36S,39R)-39-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-18-(3-amino-3-oxopropyl)-36-benzyl-12,21,33-tris(3-carbamimidamidopropyl)-27-methyl-15,30-bis(2-methylpropyl)-4,11,14,17,20,23,26,29,32,35,38,44,47-tridecaoxo-7,41,50-trithia-1,3,10,13,16,19,22,25,28,31,34,37,45-tridecazatricyclo[22.22.5.13,45]dopentacontane-9-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0196uM
(6-carbamimidoylnaphthalen-2-yl) 4-(4,5-dihydro-1H-imidazol-2-ylamino)benzoate1705182: Non-competitive inhibition of factor 12a (unknown origin) using BQGR as substrateki0.0210uM
1-[4-(bromomethyl)phenyl]-2-phenylethane-1,2-dione1798224: Enzyme Inhibition Assay from Article 10.1021/jm049011j: “Identification and characterization of novel benzil (diphenylethane-1,2-dione) analogues as inhibitors of mammalian carboxylesterases.”ki0.0213uM
1-(4-chlorophenyl)-2-(4-methylphenyl)ethane-1,2-dione1798224: Enzyme Inhibition Assay from Article 10.1021/jm049011j: “Identification and characterization of novel benzil (diphenylethane-1,2-dione) analogues as inhibitors of mammalian carboxylesterases.”ki0.0228uM
1,2-bis(3,5-difluorophenyl)ethane-1,2-dione1798224: Enzyme Inhibition Assay from Article 10.1021/jm049011j: “Identification and characterization of novel benzil (diphenylethane-1,2-dione) analogues as inhibitors of mammalian carboxylesterases.”ki0.0234uM
1-[3,5-bis(3-methylsulfanylpropanoyl)-1,3,5-triazinan-1-yl]-3-methylsulfanylpropan-1-one1802515: Protease Inhibition Assay from Article 10.1002/cbic.201600612: “Polar Hinges as Functionalized Conformational Constraints in (Bi)cyclic Peptides.”ki0.0250uM
(2S)-2-[[(2S)-2-[[(9R,12S,15S,18S,24S,27R,30S,33S,36S,39S,42R)-9-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-33-(3-amino-3-oxopropyl)-15,30,39-tris(3-carbamimidamidopropyl)-12-[(2-fluorophenyl)methyl]-18,36-bis(2-methylpropyl)-4,10,13,16,19,25,28,31,34,37,40,47,50-tridecaoxo-7,44,53-trithia-1,3,11,14,17,20,26,29,32,35,38,41,48-tridecazatetracyclo[25.22.5.13,48.020,24]pentapentacontane-42-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0268uM
(2S)-2-[[(2S)-2-[[(9R,12S,15S,18S,24S,27R,30S,33S,36S,39S,42R)-9-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-33-(3-amino-3-oxopropyl)-15,30,39-tris(3-carbamimidamidopropyl)-12,18,36-tris(2-methylpropyl)-4,10,13,16,19,25,28,31,34,37,40,47,50-tridecaoxo-7,44,53-trithia-1,3,11,14,17,20,26,29,32,35,38,41,48-tridecazatetracyclo[25.22.5.13,48.020,24]pentapentacontane-42-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0280uM
(5-amino-3-pyridin-2-yl-1,2,4-triazol-1-yl)-naphthalen-1-ylmethanone1681854: Inhibition of human coagulation factor XIIA using Boc-Gln-Gly-Arg-AMC as fluorogenic substrate measured at 1 min interval for 1 hr by fluorometric assayic500.0290uM
(2S)-2-[[(2S)-2-[[(9R,12S,15S,18S,21S,24R,27S,30S,33S,36S,39R)-39-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-18-(3-amino-3-oxopropyl)-36-benzyl-12,21,33-tris(3-carbamimidamidopropyl)-27-(hydroxymethyl)-15,30-bis(2-methylpropyl)-4,11,14,17,20,23,26,29,32,35,38,44,47-tridecaoxo-7,41,50-trithia-1,3,10,13,16,19,22,25,28,31,34,37,45-tridecazatricyclo[22.22.5.13,45]dopentacontane-9-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0294uM
(2S)-2-[[(2S)-2-[[(9R,12S,15S,18S,24S,27R,30S,33S,36S,39S,42R)-9-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-33-(3-amino-3-oxopropyl)-12-benzyl-15,30,39-tris(3-carbamimidamidopropyl)-36-(3-methylbutyl)-18-(2-methylpropyl)-4,10,13,16,19,25,28,31,34,37,40,47,50-tridecaoxo-7,44,53-trithia-1,3,11,14,17,20,26,29,32,35,38,41,48-tridecazatetracyclo[25.22.5.13,48.020,24]pentapentacontane-42-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0294uM
(2S)-2-[[(2S)-2-[[(9R,12S,15S,18S,24S,27R,30S,33S,36S,39S,42R)-9-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-33-(3-amino-3-oxopropyl)-12-benzyl-36-butyl-15,30,39-tris(3-carbamimidamidopropyl)-18-(2-methylpropyl)-4,10,13,16,19,25,28,31,34,37,40,47,50-tridecaoxo-7,44,53-trithia-1,3,11,14,17,20,26,29,32,35,38,41,48-tridecazatetracyclo[25.22.5.13,48.020,24]pentapentacontane-42-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0306uM
1-(4-nitrophenyl)-2-phenylethane-1,2-dione1798224: Enzyme Inhibition Assay from Article 10.1021/jm049011j: “Identification and characterization of novel benzil (diphenylethane-1,2-dione) analogues as inhibitors of mammalian carboxylesterases.”ki0.0306uM
1-[(4-chlorophenyl)methyl]indole-2,3-dione1798240: Enzyme Inhibition Assay from Article 10.1021/jm061471k: “Selective inhibition of carboxylesterases by isatins, indole-2,3-diones.”ki0.0320uM
(2S)-2-[[(2S)-2-[[(9R,12S,15S,18S,24S,27R,30S,33S,36S,39S,42R)-9-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-33-(3-amino-3-oxopropyl)-15,30,39-tris(3-carbamimidamidopropyl)-12-[(4-hydroxyphenyl)methyl]-18,36-bis(2-methylpropyl)-4,10,13,16,19,25,28,31,34,37,40,47,50-tridecaoxo-7,44,53-trithia-1,3,11,14,17,20,26,29,32,35,38,41,48-tridecazatetracyclo[25.22.5.13,48.020,24]pentapentacontane-42-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid1426468: Inhibition of human beta factor 12a using fluorogenic substrate Boc-Gln-Gly-Arg-AMC preincubated for 10 mins followed by addition of substrate measured every min for 30 minski0.0322uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Valproic Acidaffects cotreatment, increases expression, affects expression, decreases expression, increases methylation6
sodium arseniteaffects expression, decreases expression3
Benzo(a)pyrenedecreases expression, decreases methylation, increases expression3
Cyclosporinedecreases expression3
(+)-JQ1 compounddecreases expression2
Acetaminophendecreases expression2
Copperaffects binding, decreases expression2
Nickelaffects binding, increases expression2
Aflatoxin B1affects expression, decreases expression2
methyleugenoldecreases expression1
triphenyl phosphateaffects expression1
sulforaphanedecreases expression1
butyraldehydeincreases expression1
pentanalincreases expression1
CGP 52608affects binding, increases reaction1
entinostatincreases expression1
K 7174decreases expression1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, increases expression1
ICG 001increases expression1
abrinedecreases expression1
dorsomorphinaffects cotreatment, increases expression1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidinedecreases expression, increases response to substance1
jinfukangincreases expression1
NSC 689534affects binding, decreases expression1
Rosiglitazonedecreases expression1
Decitabineaffects expression1
Arsenic Trioxidedecreases response to substance1
Angiotensin-Converting Enzyme Inhibitorsdecreases expression1
Cadmiumaffects binding1
Chondroitin Sulfatesincreases activity1

ChEMBL screening assays

128 unique, capped per target: 123 binding, 3 functional, 2 admet

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1005173BindingInhibition of human factor 12aNovel 3-carboxamide-coumarins as potent and selective FXIIa inhibitors. — J Med Chem
CHEMBL1737911FunctionalPUBCHEM_BIOASSAY: Factor XIIa Dose Response Confirmation. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID684]PubChem BioAssay data set
CHEMBL4774638ADMETInhibition of factor 12a (unknown origin) at IC90 using kallikrein chromogenic substrate preincubated for 1 min followed by chromogenic substrate addition and measured for 2 mins in presence of AT-IIIThe components and activities analysis of a novel anticoagulant candidate dHG-5. — Eur J Med Chem

Clinical trials (associated diseases)

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

TrialPhaseStatusTitle
NCT00914966PHASE4COMPLETEDA Study to Evaluate the Safety and Effect of Escalating Doses of CINRYZE
NCT01151735PHASE4WITHDRAWNC1-INH Compared to Placebo at the Time of Prodromal Symptoms for Hereditary Angioedema (HAE) Exacerbation
NCT01457430PHASE4COMPLETEDEfficacy, Safety and Tolerability of Icatibant for the Treatment of HAE
NCT01679912PHASE4COMPLETEDA Call Center During HAE Attacks (SOS HAE)
NCT06690047PHASE4COMPLETEDTreatment of Hereditary Angioedema Prodrome with Recombinant C1-esterase Inhibitor (Ruconest)
NCT06806657PHASE4ACTIVE_NOT_RECRUITINGSafety Study in Subjects ≥ 12 Years of Age With Hereditary Angioedema Switching to Garadacimab
NCT07290855PHASE4COMPLETEDA Study to Evaluate the Safety and Efficacy of Icatibant in Patients With Bradykinin Induced Angioedema
NCT00000521PHASE4COMPLETEDSodium-Potassium Blood Pressure Trial in Children
NCT00018759PHASE4COMPLETEDTreatment Effects on Platelet Calcium in Hypertensive and Depressed Patients
NCT00034840PHASE4COMPLETEDTelmisartan vs. Valsartan in Patients With Mild to Moderate Hypertension Following a Missed Dose
NCT00044265PHASE4COMPLETEDTreatment of Pediatric Hypertension With Altace Trial
NCT00060918PHASE4COMPLETEDGlycemic Control Of Carvedilol Versus Metoprolol In Patients With Type II Diabetes Mellitus And Hypertension
NCT00060931PHASE4COMPLETEDEffect Of Carvedilol Versus Metoprolol On Glycemic Control In Patients With Type II Diabetes And Hypertension
NCT00110422PHASE4COMPLETEDIrbesartan in the Treatment of Hypertensive Patients With Metabolic Syndrome
NCT00115726PHASE4COMPLETEDTrial Assessing the Effect of Preoperative Furosemide on Intraoperative Blood Pressure
NCT00120380PHASE4TERMINATEDCombination Therapy of Bosentan and Aerosolized Iloprost in Idiopathic Pulmonary Arterial Hypertension (IPAH)
NCT00122811PHASE4UNKNOWNThe Hypertension in the Very Elderly Trial (HYVET)
NCT00123045PHASE4COMPLETEDPatient-Physician Partnership to Improve High Blood Pressure Adherence
NCT00123604PHASE4COMPLETEDVascular Effects of Carvedilol Versus Metoprolol in Hypertensive Patients With Type 2 Diabetes
NCT00126516PHASE4COMPLETEDAngiotensin II Receptor Blockers (ARB) and ACE Inhibitors (ACEI) on Silent Brain Infarction and Cognitive Decline
NCT00127348PHASE4COMPLETEDEffect of Continuous Positive Airway Pressure (CPAP) on Hypertension and Cardiovascular Morbidity-Mortality in Patients With Sleep Apnea and no Daytime Sleepiness
NCT00128518PHASE4COMPLETEDIDEAL Study: Identification of the Determinants of the Efficacy of Arterial Blood Pressure Lowering Drugs
NCT00129233PHASE4COMPLETEDComparison of Valsartan With Amlodipine in Hypertensive Patients With Glucose Intolerance
NCT00129909PHASE4COMPLETEDSTITCH (Simplified Therapeutic Intervention To Control Hypertension)
NCT00130156PHASE4COMPLETEDEffects of Combination Therapy With Alpha-1 Blocker (Bunazosin or Doxazosin) in the Treatment of Patients With Mild to Moderate Essential Hypertension
NCT00131846PHASE4COMPLETEDDiuretics In the Management of Essential Hypertension (DIME) Study
NCT00133068PHASE4COMPLETEDCollaboration to Reduce Disparities in Hypertension
NCT00133328PHASE4UNKNOWNA Morbidity-Mortality and Remodeling Study With Valsartan
NCT00133692PHASE4COMPLETEDINVEST: INternational VErapamil SR Trandolapril STudy
NCT00134160PHASE4COMPLETEDOlmeSartan and Calcium Antagonists Randomized (OSCAR) Study
NCT00136851PHASE4COMPLETEDStudy Comparing the Efficacy of Amlodipine Besylate/Benazepril Versus Amlodipine in the Treatment of Severe Hypertension
NCT00139386PHASE4COMPLETEDCandesartan for Prevention of Cardiovascular Events After Cypher or Taxus Coronary Stenting (4C) Trial
NCT00139555PHASE4COMPLETEDEffects of Amlodipine/Benazepril in Reducing Left Ventricular Hypertrophy in Patients With High Risk Hypertension
NCT00139984PHASE4COMPLETEDAmbulatory Blood Pressure Monitoring for Antihypertensive Treatment Guidance
NCT00140790PHASE4TERMINATEDValsartan in Cardiovascular Disease With Renal Dysfunction (The V-CARD) Study
NCT00140907PHASE4COMPLETEDALLOGRAFT, A Study to Evaluate the Renal Protective Effects of Losartan (0954-222)(COMPLETED)
NCT00140959PHASE4COMPLETEDLosartan and HCTZ and Amlodipine vs Atenolol and Amlodipine (0954A-309)(COMPLETED)
NCT00144144PHASE4UNKNOWNA Study on Ca Blocker Versus AII Antagonists in Hypertension With Type 2 Diabetes
NCT00144937PHASE4UNKNOWNMultifactorial Intervention on Cardiovascular Risk Factors in Subjects With Peripheral Arterial Disease
NCT00147251PHASE4COMPLETEDStop Atherosclerosis in Native Diabetics Study

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

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Sources 81

This page pulls from 81 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot