F10

Summary

F10 (coagulation factor X, HGNC:3528) is a protein-coding gene on chromosome 13q34, encoding Coagulation factor X (P00742). Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.

This gene encodes the vitamin K-dependent coagulation factor X of the blood coagulation cascade. This factor undergoes multiple processing steps before its preproprotein is converted to a mature two-chain form by the excision of the tripeptide RKR. Two chains of the factor are held together by 1 or more disulfide bonds; the light chain contains 2 EGF-like domains, while the heavy chain contains the catalytic domain which is structurally homologous to those of the other hemostatic serine proteases. The mature factor is activated by the cleavage of the activation peptide by factor IXa (in the intrisic pathway), or by factor VIIa (in the extrinsic pathway). The activated factor then converts prothrombin to thrombin in the presence of factor Va, Ca+2, and phospholipid during blood clotting. Mutations of this gene result in factor X deficiency, a hemorrhagic condition of variable severity. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing to generate mature polypeptides.

Source: NCBI Gene 2159 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital factor X deficiency (Definitive, ClinGen)
• GWAS associations: 6
• Clinical variants (ClinVar): 162 total — 17 pathogenic, 24 likely-pathogenic
• Phenotypes (HPO): 22
• Druggable target: yes — 23 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_000504

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3528
Approved symbol	F10
Name	coagulation factor X
Location	13q34
Locus type	gene with protein product
Status	Approved
Aliases	fX
Ensembl gene	ENSG00000126218
Ensembl biotype	protein_coding
OMIM	613872
Entrez	2159

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000375551, ENST00000375559, ENST00000409306, ENST00000410083, ENST00000477269, ENST00000483537, ENST00000498455, ENST00000858581, ENST00000858582, ENST00000858583

RefSeq mRNA: 3 — MANE Select: NM_000504 NM_000504, NM_001312674, NM_001312675

CCDS: CCDS81783, CCDS9530

Canonical transcript exons

ENST00000375559 — 8 exons

Exon	Start	End
ENSE00000862534	113147379	113147496
ENSE00001616173	113148916	113149529
ENSE00001885902	113122799	113122925
ENSE00003500501	113129452	113129612
ENSE00003501032	113140919	113141050
ENSE00003650233	113139357	113139470
ENSE00003683329	113143851	113144095
ENSE00003683736	113138457	113138481

Expression profiles

Bgee: expression breadth ubiquitous, 176 present calls, max score 97.19.

FANTOM5 (CAGE): breadth broad, TPM avg 6.4809 / max 357.1279, expressed in 729 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136199	6.4809	729

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	97.19	gold quality
liver	UBERON:0002107	93.73	gold quality
stromal cell of endometrium	CL:0002255	93.13	gold quality
right atrium auricular region	UBERON:0006631	90.97	gold quality
endocervix	UBERON:0000458	89.88	gold quality
ectocervix	UBERON:0012249	89.69	gold quality
mucosa of stomach	UBERON:0001199	89.13	gold quality
right ovary	UBERON:0002118	88.61	gold quality
cardiac atrium	UBERON:0002081	88.08	gold quality
left ovary	UBERON:0002119	87.33	gold quality
right coronary artery	UBERON:0001625	86.66	gold quality
left uterine tube	UBERON:0001303	86.49	gold quality
islet of Langerhans	UBERON:0000006	86.34	gold quality
skin of leg	UBERON:0001511	85.69	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.68	gold quality
apex of heart	UBERON:0002098	85.66	gold quality
right lung	UBERON:0002167	84.67	gold quality
left coronary artery	UBERON:0001626	83.26	gold quality
gall bladder	UBERON:0002110	82.89	gold quality
subcutaneous adipose tissue	UBERON:0002190	82.75	gold quality
vena cava	UBERON:0004087	82.62	silver quality
ascending aorta	UBERON:0001496	82.59	gold quality
coronary artery	UBERON:0001621	82.57	gold quality
thoracic aorta	UBERON:0001515	82.49	gold quality
aorta	UBERON:0000947	81.95	gold quality
omental fat pad	UBERON:0010414	81.85	gold quality
peritoneum	UBERON:0002358	81.82	gold quality
tibial artery	UBERON:0007610	81.77	gold quality
popliteal artery	UBERON:0002250	81.75	gold quality
body of uterus	UBERON:0009853	81.73	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-ENAD-27	yes	128.91
E-GEOD-134144	yes	37.82
E-MTAB-5061	yes	34.32
E-GEOD-81547	yes	33.57
E-HCAD-31	yes	31.12
E-GEOD-81608	yes	23.57
E-HCAD-1	yes	18.87
E-ANND-3	yes	14.61
E-GEOD-83139	yes	10.68

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA4, HNF4A, PAX3, SP1, SP3, SPI1

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• A specific pentasaccharide sequence (H5) in high affinity heparin induces a conformational change in antithrombin that is particularly important for factor Xa (fXa) inhibition (factor Xa) (PMID:11854268)
• Plasma levels of the Factor Xa (FXa)-TFPI complex were significantly higher in patients with solid tumours, compared to patients with haematological malignancy and healthy controls. (PMID:11864704)
• Structure and dynamics of zymogen human blood coagulation factor X. (PMID:11867437)
• Activation of the prothrombinase complex could be a common step of the platelet response to distinct agonists (ADP, collagen, thrombin), which may be achieved at low levels of platelet stimulation by non-aggregant doses of platelet agonists. (PMID:11914651)
• Data suggesting a physical association between factor Xa and prothrombin, and that factor Xa has an increased affinity for prothrombin in the presence of factor Va. (PMID:11983337)
• used NAPc2 as a tight binding probe of human Xa to investigate protein substrate recognition by the human prothrombinase complex. (PMID:12011050)
• Exposure of human macrophages and smooth muscle cells (SMCs) to oxidized low-density lipoprotein (oxLDL) enhances their ability to support activity of 2 major complexes of the intrinsic pathway, Xase and prothrombinase. (PMID:12036878)
• Factor X activation is regulated by sequential occupancy of a pair of linked lipid binding sites: the first recognizes diacylglycerol as the simplest effective ligand, while the second recognizes glycerophosphoserine as the minimal binding structure. (PMID:12056907)
• Factor Xa induces mitogenesis of coronary artery smooth muscle cell via activation of PAR-2. (PMID:12123809)
• Data show that factor V activation is associated with the stepwise release of the B-domain after incubation with thrombin, which results in a gradual exposure of the factor Xa-binding site. (PMID:12163491)
• There are two independent factor X binding sites on activated platelets: low affinity, high capacity (approximately 9000 sites per platelet; Kd approximately 380 nM) and low capacity, high affinity (1700 sites per platelet; Kd approximately 30 nM). (PMID:12220193)
• extended interactions between prothrombinase and substrate regions removed from the cleavage site drive substrate affinity and enforce the substrate specificity of this enzyme complex (PMID:12370181)
• A binding site for membrane-bound, activated factor X (Xa) is located on the heavy chain of factor Va; binding increases the catalytic efficiency of factor Xa toward prothrombin in the absence of factor Va. (PMID:12379114)
• prothrombinase formation is promoted by neutrophil cathepsin G in platelets (PMID:12524437)
• the Gla and first epidermal growth factor-like domains of factor X play a role in the prothrombinase and tissue factor-factor VIIa complexes. (PMID:12529356)
• A new FX mutation (Gly381Asp) in the structurally conserved serine protease active site was normally activated. It did not show detectable amidolytic activity. Mutations affecting FX activity may cause coagulation impairment & severe hemorrhage. (PMID:12574802)
• residues 404-418 in fXa provide fVa binding sites, whereas residues 557-571 in fII and 415-429 in fXa mediate interactions between fXa and fII in the prothrombinase complex (PMID:12805370)
• Factor Xa and thrombin, but not factor VIIa, induce expression of MCP-1, IL-8, IL-6 and VEGF, and expression of receptors implicated in signaling by these coagulation factors PAR-1, PAR-2 and PAR-3 in lung and dermal fibroblasts (PMID:12941034)
• findings suggest that antithrombin exosites responsible for enhancing the rates of factor Xa and factor IXa inhibition in the conformationally activated inhibitor lie in strand 3 of beta-sheet C of the serpin (PMID:14532267)
• results suggested a model by which platelet factor 4 bound to proximal (but distinct) sites to antithrombin (AT) resulting in steric interference of fXa binding to both polysaccharide and AT (PMID:14575696)
• the factor X cation-binding exosite-1 has a nonessential role in substrate and inhibitor interactions (PMID:14583605)
• FIXa/FVIIIa binding studies of coordinate binding of FVIIIa and FX to equivalent numbers of binding sites on activated platelets provide strong evidence that FVIIIa comprises the receptor that presents FX to FIXa for catalysis on the platelet membrane. (PMID:14629468)
• although charged residues of the 70-80 loop play an insignificant role in fX recognition by the factor VIIa-tissue factor complex, they are critical for the substrate recognition by factor IXa in the intrinsic Xase complex (PMID:14739327)
• model characterizes likely enzyme-binding exosites on FVIIa and Xa that may be involved in the ternary complex (sTF-VIIa-Xa) formation and the membrane binding region of the ternary complex. (PMID:14750502)
• factor X is initiated by factor IXabeta, which may play a significant role in producing Xa necessary for the procoagulant response following vascular damage (PMID:14963035)
• A new mutation (Arg251Trp) detected is responsible for defective activation via the extrinsic pathway; it may not affect protein folding and stability, but may be involved in the calcium binding site (PMID:14979399)
• direct activation of factor V by factor Xa at physiologically relevant concentrations does not appear to be a significant contributor to factor Va formation (PMID:14982929)
• The mutation Arg489Ala/Arg490Ala/Lys493Ala (489-3A) om factor VIIIa possessed near-normal affinity for FIXa and showed no effect on the Km for Factor X. (PMID:15009463)
• EGF-N of FX is required for the cofactor-dependent zymogen activation by both physiological activators, but it plays no apparent role in FXa recognition of the cofactor in the prothrombinase complex (PMID:15069066)
• the antithrombin hinge region extension is the activating conformational change for inhibition of factors IXa and Xa (PMID:15326167)
• residues Asn89, Ile90, and Val107 within loops 1 and 2 (Cys88-Cys109) of the EGF2 domain of factor IXa are essential for normal interactions with the platelet surface and for the assembly of the factor X-activating complex on activated platelets (PMID:15328360)
• These results suggest that factor Va interacts with 185-189-loop for fXa, which is energetically linked to the Na(+)-binding site of the protease. (PMID:15347660)
• propose that ordered bond cleavage results from the constraints associated with the binding of prothrombin substrates in one of two conformations to a single form of prothrombinase (PMID:15494418)
• FXa may contribute to proinflammatory changes in acute myocardial infarction by stimulation of IL-8 release. In vitro factor Xa stimulated IL-8 & monocyte chemoattractant protein-1 release & RNA expression by activation of protease-activated receptor 1. (PMID:15550696)
• thrombin formation by B16F10 melanoma cell-bound human factor Xa was enhanced approximately 10 fold in the presence of factor Va, indicating the assembly of prothrombinase complex. (PMID:15567463)
• EGF-like domains of factor Xa and factor IXa are important for the activation of the factor VII–tissue factor complex (PMID:15634274)
• Phosphatidylserine-induced formation of the coagulation factor Xa-factor Va (FVa) complex or its activity does not require occupancy of FVa C2-domain lipid binding pocket. (PMID:15641797)
• factor Xa can induce mesangial cell proliferation through the activation of ERK via PAR2 in mesangial cells. (PMID:15882255)
• analysis of molecular basis of FX deficiency in patients from the Indian subcontinent: six novel mutations including triple heterozygosity for Phe31Ser, 514delT and 516T–>G factor X gene mutations (PMID:15892863)
• the interaction of factor Xa with the heavy chain of factor Va strongly influences the catalytic activity of the enzyme resulting in increased rates for both prothrombin-activating cleavages. (PMID:15897196)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	f10	ENSDARG00000088581
mus_musculus	F10	ENSMUSG00000031444
rattus_norvegicus	F10	ENSRNOG00000033444

Paralogs (16): F7 (ENSG00000057593), F11 (ENSG00000088926), F9 (ENSG00000101981), HGFAC (ENSG00000109758), 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 X — P00742 (reviewed: P00742)

Alternative names: Stuart factor, Stuart-Prower factor

All UniProt accessions (5): P00742, B7ZBK1, F8WBM7, Q5JVE7, Q5JVE8

UniProt curated annotations — full annotation on UniProt →

Function. Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting. Factor Xa activates pro-inflammatory signaling pathways in a protease-activated receptor (PAR)-dependent manner. Up-regulates expression of protease-activated receptors (PARs) F2R, F2RL1 and F2RL2 in dermal microvascular endothelial cells. Triggers the production of pro-inflammatory cytokines, such as MCP-1/CCL2 and IL6, in cardiac fibroblasts and umbilical vein endothelial cells in PAR-1/F2R-dependent manner. Triggers the production of pro-inflammatory cytokines, such as MCP-1/CCL2, IL6, TNF/TNF, IL-1beta/IL1B, IL8/CXCL8 and IL18, in endothelial cells and atrial tissues. Induces expression of adhesion molecules, such as ICAM1, VCAM1 and SELE, in endothelial cells and atrial tissues. Increases expression of phosphorylated ERK1/2 in dermal microvascular endothelial cells and atrial tissues. Triggers activation of the transcription factor NF-kappa-B in dermal microvascular endothelial cells and atrial tissues. Activates pro-inflammatory and pro-fibrotic responses in dermal fibroblasts and enhances wound healing probably via PAR-2/F2RL1-dependent mechanism. Activates barrier protective signaling responses in endothelial cells in PAR-2/F2RL1-dependent manner; the activity depends on the cleavage of PAR-2/F2RL1 by factor Xa. Up-regulates expression of plasminogen activator inhibitor 1 (SERPINE1) in atrial tissues.

Subunit / interactions. The two chains are formed from a single-chain precursor by the excision of two Arg residues and are held together by 1 or more disulfide bonds. Forms a heterodimer with SERPINA5. Interacts (inactive and activated) with ixolaris, an anticoagulant protein from Ixodes scapularis saliva. Interacts (activated) with iripin-8, a serine protease inhibitor from Ixodes ricinus saliva. Interacts (activated) with FXa-directed anticoagulant from Aedes albopictus saliva. Interacts (activated) with guianensin, an anticoagulant protein from Simulium guianense saliva. Interacts (activated) with simukunin, an anticoagulant protein from Simulium vittatum saliva. (Microbial infection) Interacts (via Gla domain) with Human adenovirus C serotype 5 hexon protein; this interaction allows the virus to be shielded from its host immune system.

Subcellular location. Secreted.

Tissue specificity. Plasma; synthesized in the liver.

Post-translational modifications. Carboxylated by vitamin K-dependent GGCX to form gamma-carboxyglutamate; these residues are essential for the binding of calcium. N- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans. Proteolytically cleaved and activated by cathepsin CTSG. The activation peptide is cleaved by factor IXa (in the intrinsic pathway), or by factor VIIa (in the extrinsic pathway). The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.

Disease relevance. Factor X deficiency (FA10D) [MIM:227600] A hemorrhagic disease with variable presentation. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. Some patients do not have clinical bleeding diathesis. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by SERPINA5 and SERPINA10.

Similarity. Belongs to the peptidase S1 family.

RefSeq proteins (3): NP_000495, NP_001299603, NP_001299604 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000294	GLA_domain	Domain
IPR000742	EGF	Domain
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR012224	Pept_S1A_FX	Family
IPR017857	Coagulation_fac-like_Gla_dom	Homologous_superfamily
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR035972	GLA-like_dom_SF	Homologous_superfamily
IPR043504
IPR050442	Peptidase_S1_coag_factors	Family

Pfam: PF00008, PF00089, PF00594, PF14670

Enzyme classification (BRENDA):

• EC 3.4.21.6 — coagulation factor Xa (BRENDA: 13 organisms, 177 substrates, 1010 inhibitors, 101 Km, 85 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
PROTHROMBIN	—	25
METHOXYCARBONYLCYCLOHEXYL-GLY-GLY-L-ARG-4-NITROA	0.072–1.38	8
N-ALPHA-BENZYLOXYCARBONYL-D-ARGINYL-GLYCYL-L-ARG	0.042–0.122	8
ARG-GLY-ARG-4-NITROANILIDE	0.0507–3.9	7
S2222	0.133–0.739	6
S2765	0.052–0.112	5
L-ARG-GLY-L-ARG-4-NITROANILIDE	0.036–0.24	4
PRETHROMBIN-1	0.0052–0.0069	4
BENZOYL-ILE-GLU(PIPERIDINEAMIDE)-GLY-ARG-P-NITRO	0.0867–0.0965	3
BENZOYL-ILE-GLU-(-H/OME)-GLY-ARG-P-NITROANILIDE	0.175–0.189	2
FRAGMENT 1.2:PRETHROMBIN-2	0.0006–0.0008	2
MEIZOTHROMBIN	0.0006–0.0009	2
RECOMBINANT PROTHROMBIN R155A/R284A/R271A MUTANT	0.0004	2
RECOMBINANT PROTHROMBIN R155A/R284A/R320A MUTANT	0.0004–0.0005	2
TOSYL-GLYCYL-PROLYL-D-ARGININE-4-NITROANILIDE	0.097–0.206	2

UniProt features (144 total): strand 36, sequence variant 33, mutagenesis site 14, modified residue 12, disulfide bond 12, turn 8, helix 7, domain 4, chain 4, glycosylation site 4, active site 3, propeptide 2, region of interest 2, sequence conflict 2, signal peptide 1

Structure

Experimental structures (PDB)

188 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9I24	X-RAY DIFFRACTION	1.2
2JKH	X-RAY DIFFRACTION	1.25
2Y5F	X-RAY DIFFRACTION	1.29
2Y5G	X-RAY DIFFRACTION	1.29
2Y5H	X-RAY DIFFRACTION	1.33
3KL6	X-RAY DIFFRACTION	1.45
2PR3	X-RAY DIFFRACTION	1.5
6YYX	X-RAY DIFFRACTION	1.53
3FFG	X-RAY DIFFRACTION	1.54
7YB9	X-RAY DIFFRACTION	1.54
4Y6D	X-RAY DIFFRACTION	1.55
2VWO	X-RAY DIFFRACTION	1.6
3CEN	X-RAY DIFFRACTION	1.6
9FVV	X-RAY DIFFRACTION	1.6
2VWN	X-RAY DIFFRACTION	1.61
2P3U	X-RAY DIFFRACTION	1.62
6Q9F	X-RAY DIFFRACTION	1.63
2BOK	X-RAY DIFFRACTION	1.64
2XBV	X-RAY DIFFRACTION	1.66
7BMI	X-RAY DIFFRACTION	1.66
2XC4	X-RAY DIFFRACTION	1.67
7YBB	X-RAY DIFFRACTION	1.68
2VH0	X-RAY DIFFRACTION	1.7
2XC5	X-RAY DIFFRACTION	1.7
2Y81	X-RAY DIFFRACTION	1.7
8RE5	X-RAY DIFFRACTION	1.7
9FVU	X-RAY DIFFRACTION	1.7
2XBW	X-RAY DIFFRACTION	1.72
2VVV	X-RAY DIFFRACTION	1.73
2UWO	X-RAY DIFFRACTION	1.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00742-F1	80.47	0.55

Antibody-complex structures (SAbDab): 2 — 7AHU, 9P0X

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): 276 (charge relay system); 322 (charge relay system); 419 (charge relay system)

Post-translational modifications (12): 46, 47, 54, 56, 59, 60, 65, 66, 69, 72, 79, 103

Disulfide bonds (12): 57–62, 90–101, 95–110, 112–121, 129–140, 136–149, 151–164, 172–342, 241–246, 261–277, 390–404, 415–443

Glycosylation sites (4): 199, 211, 221, 231

Mutagenesis-validated functional residues (14):

Position	Phenotype
255	reduces activity for cleavage of par-2/f2rl1. no significant effects on factor va (f5) binding and activity toward proth
256	reduces activity for cleavage of par-2/f2rl1. no significant effects on factor va (f5) binding and activity toward proth
258	reduces activity for cleavage of par-2/f2rl1. no significant effects on factor va (f5) binding and activity toward proth
282	reduces activity for cleavage of par-2/f2rl1. no significant effects on factor va (f5) binding and activity toward proth
283	reduces activity for cleavage of par-2/f2rl1. no significant effects on factor va (f5) binding and activity toward proth
306	no significant effects on activity for cleavage of par-2/f2rl1.
310	no significant effects on activity for cleavage of par-2/f2rl1.
345	no significant effects on activity for cleavage of par-2/f2rl1.
350	no significant effects on activity for cleavage of par-2/f2rl1.
366	reduces activity for cleavage of par-2/f2rl1.
372	reduces activity for cleavage of par-2/f2rl1.
376	reduces activity for cleavage of par-2/f2rl1.
387	reduces activity for cleavage of par-2/f2rl1.
391	reduces activity for cleavage of par-2/f2rl1.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-159740	Gamma-carboxylation of protein precursors
R-HSA-159763	Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus
R-HSA-159782	Removal of aminoterminal propeptides from gamma-carboxylated proteins
R-HSA-9672383	Defective factor IX causes thrombophilia
R-HSA-9672396	Defective cofactor function of FVIIIa variant
R-HSA-9673202	Defective F9 variant does not activate FX
R-HSA-9769735	Initiation of coagulation cascade
R-HSA-9769739	Regulation of clotting cascade
R-HSA-9769743	Amplification and propagation of coagulation cascade
R-HSA-140834
R-HSA-140837
R-HSA-140875

MSigDB gene sets: 241 (showing top): MODULE_172, GOBP_PROTEIN_ACTIVATION_CASCADE, GNF2_GSTM1, GNF2_HPN, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_POSITIVE_REGULATION_OF_TOR_SIGNALING, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOCC_CELL_SURFACE, GOBP_WOUND_HEALING, GOBP_PROTEIN_MATURATION, REACTOME_GAMMA_CARBOXYLATION_TRANSPORT_AND_AMINO_TERMINAL_CLEAVAGE_OF_PROTEINS, FOSTER_TOLERANT_MACROPHAGE_DN, MODULE_109, chr13q34

GO Biological Process (5): proteolysis (GO:0006508), blood coagulation (GO:0007596), positive regulation of cell migration (GO:0030335), positive regulation of TOR signaling (GO:0032008), hemostasis (GO:0007599)

GO Molecular Function (7): serine-type endopeptidase activity (GO:0004252), calcium ion binding (GO:0005509), phospholipid binding (GO:0005543), 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), endoplasmic reticulum lumen (GO:0005788), Golgi lumen (GO:0005796), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Gamma-carboxylation, transport, and amino-terminal cleavage of proteins	3
Coagulation pathway	3
Defects of Coagulation cascade	1
Defective factor VIII causes hemophilia A	1
Defective factor IX causes hemophilia B	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular organelle lumen	2
protein metabolic process	1
hemostasis	1
wound healing	1
coagulation	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
TOR signaling	1
regulation of TOR signaling	1
positive regulation of intracellular signal transduction	1
regulation of body fluid levels	1
endopeptidase activity	1
serine-type peptidase activity	1
metal ion binding	1
lipid binding	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
serine hydrolase activity	1
catalytic activity	1
cellular anatomical structure	1
endoplasmic reticulum	1
Golgi apparatus	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1

Protein interactions and networks

STRING

1262 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
F10	F3	P13726	998
F10	TFPI	P10646	996
F10	F8	P00451	987
F10	F2	P00734	972
F10	PROCR	Q9UNN8	958
F10	EPRS1	P07814	940
F10	NR1I2	O75469	820
F10	F5	P12259	797
F10	VWF	P04275	791
F10	RHAG	Q02094	781
F10	UMPS	P11172	761
F10	F7	P08709	744
F10	SERPINC1	P01008	730
F10	HRG	P04196	696
F10	KNG1	P01042	684

IntAct

31 interactions, top by confidence:

A	B	Type	Score
IKBKG	IKBKB	psi-mi:“MI:0914”(association)	0.980
PIK3CA	PIK3R2	psi-mi:“MI:0914”(association)	0.900
TAB1	MAP3K7	psi-mi:“MI:0914”(association)	0.900
SERPINA10	F10	psi-mi:“MI:0407”(direct interaction)	0.560
F10	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
F10	NOTCH2NLC	psi-mi:“MI:0915”(physical association)	0.560
F10	L3	psi-mi:“MI:0407”(direct interaction)	0.440
F10		psi-mi:“MI:0407”(direct interaction)	0.440
	F10	psi-mi:“MI:0407”(direct interaction)	0.440
eco	F10	psi-mi:“MI:0407”(direct interaction)	0.440
F10	PCOLCE	psi-mi:“MI:0407”(direct interaction)	0.440
IX	F10	psi-mi:“MI:0915”(physical association)	0.400
PB2		psi-mi:“MI:0914”(association)	0.350
CHAMP1	F2	psi-mi:“MI:0914”(association)	0.350
F10	PIP4P1	psi-mi:“MI:0914”(association)	0.350
VEGFD	RPSA2	psi-mi:“MI:0914”(association)	0.350
TMEM106A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
BTNL2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SFTPC	TMEM131L	psi-mi:“MI:0914”(association)	0.350
LY86	TMEM131L	psi-mi:“MI:0914”(association)	0.350
DNAJB9	POTEF	psi-mi:“MI:0914”(association)	0.350
SDF2L1	MANBA	psi-mi:“MI:0914”(association)	0.350
F10	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000
F10	NOTCH2NLC	psi-mi:“MI:0915”(physical association)	0.000
F10	PRKAB1	psi-mi:“MI:0915”(physical association)	0.000
F10	H1-2	psi-mi:“MI:0915”(physical association)	0.000
F10	MGST3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (33): PRKAB1 (Two-hybrid), UBQLN2 (Two-hybrid), NOTCH2NL (Two-hybrid), NBPF19 (Two-hybrid), SERPINB8 (Reconstituted Complex), F7 (Biochemical Activity), F5 (Reconstituted Complex), F8 (Reconstituted Complex), S (Biochemical Activity), F10 (Affinity Capture-MS), F10 (Affinity Capture-MS), F10 (Affinity Capture-MS), S (Biochemical Activity), S (Reconstituted Complex), F10 (Affinity Capture-Western)

ESM2 similar proteins: A6H6T1, A6MFK7, A6MFK8, O15393, O19045, O70169, P00741, P00742, P00749, P04185, P15638, P16227, P18292, P19221, P31394, P33587, P49150, P57727, P70375, P98119, P98121, Q05589, Q14520, Q1L658, Q1L659, Q3UQ41, Q4QXT9, Q56VR3, Q58L93, Q58L94, Q58L95, Q58L96, Q5E9Z2, Q5R537, Q5RF29, Q5U405, Q6AXZ6, Q6AY28, Q6DIV5, Q6L711

Diamond homologs: A0A1S4H5M5, A0A1S4H5S2, A0A6I8TBG6, A0A6J1W8N1, A6MFK7, A6MFK8, B8V7S0, F5HKX0, O18783, O19045, O88947, O97366, P00740, P00741, P00742, P00743, P00745, P00747, P00761, P03951, P06868, P08217, P12545, P14272, P15944, P16293, P16295, P19236, P19540, P20231, P21845, P26262, P27435, P31394, P33587, P35033, P35041, P50342, P50343, P56677

SIGNOR signaling

25 interactions.

A	Effect	B	Mechanism
apixaban	down-regulates	F10	“chemical inhibition”
BMS-740808	down-regulates	F10	“chemical inhibition”
rivaroxaban	down-regulates	F10	“chemical inhibition”
F10	“up-regulates activity”	F7	cleavage
“Factor FVIIa:TF”	“up-regulates activity”	F10	binding
F7	“up-regulates activity”	F10	binding
GGCX	“up-regulates activity”	F10	carboxylation
“Factor VIIIa-IXa”	“up-regulates activity”	F10	cleavage
F10	“up-regulates activity”	F2	cleavage
betrixaban	“down-regulates activity”	F10	“chemical inhibition”
edoxaban	“down-regulates activity”	F10	“chemical inhibition”
F10	“form complex”	“Factor Va-Xa”	binding
SERPINC1	“down-regulates activity”	F10	cleavage
F10	“down-regulates activity”	APOH	cleavage

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 31 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Downstream TCR signaling	5	30.6×	4e-05
Innate Immune System	6	7.3×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
T cell receptor signaling pathway	5	28.1×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	24
Uncertain significance	74
Likely benign	10
Benign	21

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1098484	NM_000504.4(F10):c.513del (p.Cys172fs)	Pathogenic
12053	NM_000504.4(F10):c.1096C>T (p.Arg366Cys)	Pathogenic
12054	NM_000504.4(F10):c.814del (p.Ile271_Leu272insTer)	Pathogenic
12056	NM_000504.4(F10):c.1012G>A (p.Val338Met)	Pathogenic
12057	NM_000504.4(F10):c.1147C>T (p.Pro383Ser)	Pathogenic
12058	NM_000504.4(F10):c.61G>A (p.Gly21Arg)	Pathogenic
12059	NM_000504.4(F10):c.859A>T (p.Arg287Trp)	Pathogenic
12060	NM_000504.4(F10):c.1120T>C (p.Ser374Pro)	Pathogenic
12062	NM_000504.4(F10):c.964G>A (p.Asp322Asn)	Pathogenic
12066	NM_000504.4(F10):c.865G>C (p.Gly289Arg)	Pathogenic
1341356	NM_000504.4(F10):c.1216G>A (p.Gly406Ser)	Pathogenic
1684308	NM_000504.4(F10):c.162_163del (p.Glu56fs)	Pathogenic
1684490	NM_000504.4(F10):c.837C>A (p.Tyr279Ter)	Pathogenic
3340672	NM_000504.4(F10):c.1382G>A (p.Trp461Ter)	Pathogenic
3573027	NM_000504.4(F10):c.307G>C (p.Asp103His)	Pathogenic
3765278	NM_000504.4(F10):c.730G>A (p.Gly244Arg)	Pathogenic
4845820	NM_000504.4(F10):c.71-1G>C	Pathogenic
1067302	NM_000504.4(F10):c.257-1G>C	Likely pathogenic
1163549	NM_000504.4(F10):c.1247A>T (p.Gln416Leu)	Likely pathogenic
1679953	NM_000504.4(F10):c.1073C>T (p.Thr358Met)	Likely pathogenic
1684307	NM_000504.4(F10):c.205G>A (p.Glu69Lys)	Likely pathogenic
1684309	NM_000504.4(F10):c.1252G>C (p.Asp418His)	Likely pathogenic
1703258	NM_000504.4(F10):c.232-2563_503-451del	Likely pathogenic
2505497	NM_000504.4(F10):c.270T>A (p.Cys90Ter)	Likely pathogenic
2505498	NM_000504.4(F10):c.256G>A (p.Asp86Asn)	Likely pathogenic
2505499	NM_000504.4(F10):c.167A>G (p.Glu56Gly)	Likely pathogenic
2505500	NM_000504.4(F10):c.248_251del (p.Lys83fs)	Likely pathogenic
2505501	NM_000504.4(F10):c.299_300del (p.Lys100fs)	Likely pathogenic
2505502	NM_000504.4(F10):c.305_306del (p.Lys102fs)	Likely pathogenic
2572121	NM_000504.4(F10):c.119G>C (p.Arg40Thr)	Likely pathogenic

SpliceAI

1567 predictions. Top by Δscore:

Variant	Effect	Δscore
13:113122923:GTC:G	donor_gain	1.0000
13:113122926:G:GG	donor_gain	1.0000
13:113129450:A:AG	acceptor_gain	1.0000
13:113129450:AGT:A	acceptor_gain	1.0000
13:113129451:G:GA	acceptor_gain	1.0000
13:113129451:GT:G	acceptor_gain	1.0000
13:113129451:GTG:G	acceptor_gain	1.0000
13:113129451:GTGT:G	acceptor_gain	1.0000
13:113129451:GTGTT:G	acceptor_gain	1.0000
13:113140917:A:AG	acceptor_gain	1.0000
13:113140918:G:GC	acceptor_gain	1.0000
13:113140918:GT:G	acceptor_gain	1.0000
13:113140918:GTC:G	acceptor_gain	1.0000
13:113140918:GTCA:G	acceptor_gain	1.0000
13:113140918:GTCAC:G	acceptor_gain	1.0000
13:113141048:CAGG:C	donor_loss	1.0000
13:113141049:AGGTA:A	donor_loss	1.0000
13:113141050:GG:G	donor_loss	1.0000
13:113141051:G:T	donor_loss	1.0000
13:113144050:G:GT	donor_gain	1.0000
13:113144066:G:GT	donor_gain	1.0000
13:113144075:G:GT	donor_gain	1.0000
13:113144080:G:GT	donor_gain	1.0000
13:113144080:G:T	donor_gain	1.0000
13:113122920:A:T	donor_gain	0.9900
13:113129609:GACG:G	donor_gain	0.9900
13:113139454:C:T	donor_gain	0.9900
13:113139471:G:GG	donor_gain	0.9900
13:113140914:TGCA:T	acceptor_loss	0.9900
13:113140915:GCA:G	acceptor_loss	0.9900

AlphaMissense

3253 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:113147413:G:A	C261Y	0.999
13:113147462:T:G	C277W	0.999
13:113149015:A:T	D322V	0.999
13:113149134:A:C	S362R	0.999
13:113149136:C:A	S362R	0.999
13:113149136:C:G	S362R	0.999
13:113149218:T:A	C390S	0.999
13:113149219:G:C	C390S	0.999
13:113149260:T:A	C404S	0.999
13:113149261:G:C	C404S	0.999
13:113149293:T:A	C415S	0.999
13:113149294:G:A	C415Y	0.999
13:113149294:G:C	C415S	0.999
13:113149308:G:T	G420W	0.999
13:113149377:T:A	C443S	0.999
13:113149378:G:C	C443S	0.999
13:113144090:T:A	W248R	0.998
13:113144090:T:C	W248R	0.998
13:113144092:G:C	W248C	0.998
13:113144092:G:T	W248C	0.998
13:113147413:G:T	C261F	0.998
13:113147414:T:G	C261W	0.998
13:113147460:T:C	C277R	0.998
13:113147461:G:A	C277Y	0.998
13:113149015:A:C	D322A	0.998
13:113149020:G:C	A324P	0.998
13:113149140:T:C	F364L	0.998
13:113149142:C:A	F364L	0.998
13:113149142:C:G	F364L	0.998
13:113149219:G:A	C390Y	0.998

dbSNP variants (sampled 300 via entrez): RS1000076445 (13:113146173 G>A), RS1000174970 (13:113130379 A>AG), RS1000233802 (13:113123566 C>T), RS1000258618 (13:113139530 C>A,G,T), RS1000470416 (13:113123817 C>A), RS1000518502 (13:113135392 G>A), RS1000729549 (13:113141492 G>C), RS1000820397 (13:113145604 A>G), RS1000842113 (13:113122570 T>G), RS1000905329 (13:113128515 C>T), RS1000935800 (13:113128100 A>G), RS1001026688 (13:113145319 C>A,G,T), RS1001120081 (13:113133877 A>T), RS1001421881 (13:113135270 A>C), RS1001448291 (13:113134303 C>T)

Disease associations

OMIM: gene MIM:613872 | disease phenotypes: MIM:227600

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital factor X deficiency	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
congenital factor X deficiency	Definitive	AR

Mondo (3): factor X deficiency (MONDO:0002247), congenital factor X deficiency (MONDO:0009212), thrombocytopenia (MONDO:0002049)

Orphanet (1): Congenital factor X deficiency (Orphanet:328)

HPO phenotypes

22 total (22 of 22 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000132	Menorrhagia
HP:0000225	Gingival bleeding
HP:0000421	Epistaxis
HP:0000790	Hematuria
HP:0000978	Bruising susceptibility
HP:0002138	Subarachnoid hemorrhage
HP:0002170	Intracranial hemorrhage
HP:0002239	Gastrointestinal hemorrhage
HP:0003645	Prolonged partial thromboplastin time
HP:0004846	Prolonged bleeding after surgery
HP:0005261	Joint hemorrhage
HP:0006298	Prolonged bleeding after dental extraction
HP:0007420	Spontaneous hematomas
HP:0008151	Prolonged prothrombin time
HP:0008321	Reduced factor X activity
HP:0011854	Hemoperitoneum
HP:0011884	Abnormal umbilical stump bleeding
HP:0011891	Post-partum hemorrhage
HP:0012233	Intramuscular hematoma
HP:0025328	Antepartum hemorrhage
HP:0030140	Oral cavity bleeding

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000082_1	Factor VII	5.000000e-16
GCST006585_651	Blood protein levels	2.000000e-06
GCST006585_652	Blood protein levels	6.000000e-06
GCST008103_78	Bipolar disorder	1.000000e-06
GCST90002385_18	High light scatter reticulocyte count	1.000000e-09
GCST90002386_161	High light scatter reticulocyte percentage of red cells	3.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004619	factor VII measurement
EFO:0007986	reticulocyte count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D005171	Factor X Deficiency	C15.378.100.100.320; C15.378.100.141.320; C15.378.463.320; C16.320.099.320
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (8): CHEMBL2111401 (SELECTIVITY GROUP), CHEMBL2111412 (SELECTIVITY GROUP), CHEMBL2111419 (SELECTIVITY GROUP), CHEMBL2111424 (SELECTIVITY GROUP), CHEMBL2111449 (PROTEIN COMPLEX), CHEMBL244 (SINGLE PROTEIN), CHEMBL5482991 (PROTEIN COMPLEX), CHEMBL6066543 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

23 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 95,362 (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
CHEMBL1166	ARGATROBAN	4	231
CHEMBL1200644	FONDAPARINUX SODIUM	4	12,630
CHEMBL1201202	FONDAPARINUX	4	140
CHEMBL1269025	EDOXABAN	4	2,356
CHEMBL198362	RIVAROXABAN	4	11,497
CHEMBL231779	APIXABAN	4	9,262
CHEMBL266349	MELAGATRAN	4	5,421
CHEMBL512351	BETRIXABAN	4	1,084
CHEMBL55	PENTAMIDINE	4	27,049
CHEMBL1922235	DAREXABAN	3	710
CHEMBL273264	NAFAMOSTAT	3	7,063
CHEMBL46618	OTAMIXABAN	3	526
CHEMBL48361	DABIGATRAN	3	13,443
CHEMBL87563	GABEXATE	3	2,031
CHEMBL1095032	LETAXABAN	2	375
CHEMBL1270156	TANOGITRAN	2	95
CHEMBL1271162	LY-517717	2	38
CHEMBL206335	RAZAXABAN	2	301
CHEMBL220050	GW813893	2	73
CHEMBL273196	EFEGATRAN	2	1,037
CHEMBL3139247	SEGATROXABAN	2
CHEMBL476186	ERIBAXABAN	2
CHEMBL73193	FIDEXABAN	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Blood coagulation components

Most potent curated ligand interactions (11 total), top 11:

Ligand	Action	Affinity	Parameter
apixaban	Inhibition	10.1	pKi
betrixaban	Inhibition	9.93	pKi
otamixaban	Inhibition	9.4	pKi
rivaroxaban	Inhibition	9.4	pKi
zifaxaban	Inhibition	9.3	pKi
edoxaban	Inhibition	9.25	pKi
eribaxaban	Inhibition	9.24	pIC50
BAY 3389934	Inhibition	9.15	pIC50
JTV-803	Inhibition	7.72	pKi
DX-9065a	Inhibition	7.39	pKi
emicizumab	Binding	5.73	pKd

Binding affinities (BindingDB)

1464 measured of 1566 human assays (1569 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[3,4-dihydro-2H-pyrrol-5-yl(methyl)amino]methyl}thiophene-2-carboxamide	KI	0.004 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[2-(methylsulfanyl)-4,5-dihydro-1H-imidazol-1-yl]methyl}thiophene-2-carboxamide	KI	0.004 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-(4,5-dihydro-1H-imidazol-1-ylmethyl)thiophene-2-carboxamide	KI	0.004 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[2-(ethylamino)-1H-imidazol-1-yl]methyl}thiophene-2-carboxamide	KI	0.005 nM
4-[(2-amino-1H-imidazol-1-yl)methyl]-3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}thiophene-2-carboxamide	KI	0.006 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[2-(propan-2-ylamino)-1H-imidazol-1-yl]methyl}thiophene-2-carboxamide	KI	0.008 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-[(2-imino-1,3-oxazolidin-3-yl)methyl]thiophene-2-carboxamide	KI	0.01 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-[(2-imino-1,3-thiazolidin-3-yl)methyl]thiophene-2-carboxamide	KI	0.01 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-[(2-iminoimidazolidin-1-yl)methyl]thiophene-2-carboxamide	KI	0.01 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-[(2-methyl-4,5-dihydro-1H-imidazol-1-yl)methyl]thiophene-2-carboxamide	KI	0.01 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-[(N-methylethanimidamido)methyl]thiophene-2-carboxamide	KI	0.01 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-(3-methylcarbamimidamidomethyl)thiophene-2-carboxamide	KI	0.01 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-[(2-methyl-1H-imidazol-1-yl)methyl]thiophene-2-carboxamide	KI	0.01 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[4,5-dihydro-1,3-oxazol-2-yl(ethyl)amino]methyl}thiophene-2-carboxamide	KI	0.012 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[5,6-dihydro-4H-1,3-oxazin-2-yl(methyl)amino]methyl}thiophene-2-carboxamide	KI	0.012 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-({methyl[2-(pyrrolidin-1-yl)ethyl]amino}methyl)thiophene-2-carboxamide	KI	0.019 nM
4-{[2-(4-{[1-(3-amino-1,2-benzoxazol-5-yl)-3-(trifluoromethyl)-1H-pyrazole-5-]amido}-3-fluorophenyl)phenyl]methyl}-4-methylmorpholin-4-ium bromide	KI	0.02 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[(ethylcarbamoyl)(methyl)amino]methyl}thiophene-2-carboxamide	KI	0.02 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[1H-imidazol-2-yl(methyl)amino]methyl}thiophene-2-carboxamide	KI	0.02 nM
3-[({[4-chloro-5-({4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}carbamoyl)thiophen-3-yl]methyl}(methyl)carbamoyl)amino]propanoic acid	KI	0.022 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-(1H-imidazol-1-ylmethyl)thiophene-2-carboxamide	KI	0.022 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-({3-(dimethylamino)propylamino}methyl)thiophene-2-carboxamide	KI	0.024 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[4,5-dihydro-1,3-thiazol-2-yl(methyl)amino]methyl}thiophene-2-carboxamide	KI	0.024 nM
4-{[carbamoyl(methyl)amino]methyl}-3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}thiophene-2-carboxamide	KI	0.026 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[methyl(4-oxo-4,5-dihydro-1,3-oxazol-2-yl)amino]methyl}thiophene-2-carboxamide	KI	0.026 nM
1-(3-amino-1,2-benzoxazol-5-yl)-6-[4-(2-{[(3R)-3-hydroxypyrrolidin-1-yl]methyl}phenyl)phenyl]-3-(trifluoromethyl)-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridin-7-one	KI	0.03 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[ethyl(4-methyl-4,5-dihydro-1,3-oxazol-2-yl)amino]methyl}thiophene-2-carboxamide	KI	0.031 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-[(2-imino-4-oxoimidazolidin-1-yl)methyl]thiophene-2-carboxamide	KI	0.034 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[methyl({[2-(pyrrolidin-1-yl)ethyl]carbamoyl})amino]methyl}thiophene-2-carboxamide	KI	0.036 nM
1-(3-amino-1,2-benzoxazol-5-yl)-6-(4-{2-[(dimethylamino)methyl]phenyl}phenyl)-3-(trifluoromethyl)-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridin-7-one	KI	0.04 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[methane(methyl)sulfonamido]methyl}thiophene-2-carboxamide	KI	0.045 nM
{[2-(4-{[1-(3-amino-1,2-benzoxazol-5-yl)-3-(trifluoromethyl)-1H-pyrazole-5-]amido}-3-fluorophenyl)phenyl]methyl}trimethylazanium bromide	KI	0.05 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-({(2-hydroxyethyl)carbamoylamino}methyl)thiophene-2-carboxamide	KI	0.05 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[methyl(1,3-oxazol-2-yl)amino]methyl}thiophene-2-carboxamide	KI	0.059 nM
1-{[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl}-3-cyano-7-methyl-N-[1-(propan-2-yl)piperidin-4-yl]-1H-indole-2-carboxamide	KI	0.07 nM
6-[4-(2-{[(3R)-3-hydroxypyrrolidin-1-yl]methyl}phenyl)phenyl]-1-(4-methoxyphenyl)-7-oxo-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridine-3-carboxamide	KI	0.07 nM
1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridine-3-carboxamide	KI	0.075 nM
1-{[2-(4-{[1-(3-amino-1,2-benzoxazol-5-yl)-3-(trifluoromethyl)-1H-pyrazole-5-]amido}-3-fluorophenyl)phenyl]methyl}pyridin-1-ium bromide	KI	0.08 nM
6-(4-{2-[(diethylamino)methyl]phenyl}phenyl)-1-(4-methoxyphenyl)-7-oxo-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridine-3-carboxamide	KI	0.08 nM
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-7-nitro-1H-indole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide	KI	0.1 nM
Razaxaban Analogue	KI	0.1 nM
1-(3-amino-1,2-benzoxazol-5-yl)-N-{2-fluoro-4-[2-(pyrrolidin-1-ylmethyl)phenyl]phenyl}-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide	KI	0.1 nM
bicyclic pyrazole scaffold	KI	0.11 nM
1-(3-amino-1,2-benzoxazol-5-yl)-6-[4-(2-{[(3R)-3-hydroxypyrrolidin-1-yl]methyl}phenyl)phenyl]-3-(trifluoromethyl)-1H,4H,5H,6H,7H-pyrazolo[4,3-d]pyrimidine-5,7-dione	KI	0.11 nM
1-[2-(5-carbamimidoyl-2-hydroxyphenoxy)-3,5-difluoro-6-[3-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)phenoxy]pyridin-4-yl]piperidine-3-carboxylic acid	KI	0.11 nM
2-{2-(5-carbamimidoyl-2-hydroxyphenoxy)-3,5-difluoro-6-[3-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)phenoxy]pyridin-4-ylamino}acetic acid	KI	0.11 nM
1-(3-amino-1,2-benzoxazol-5-yl)-6-[4-(2-{[(3S)-3-hydroxypyrrolidin-1-yl]methyl}phenyl)phenyl]-3-(trifluoromethyl)-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridin-7-one	KI	0.12 nM
2-{6-[4-(2-methanesulfonylphenyl)phenyl]-7-oxo-3-(trifluoromethyl)-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridin-1-yl}-5-methoxybenzene-1-sulfonamide	KI	0.12 nM
4-{[tert-butyl(4,5-dihydro-1,3-oxazol-2-yl)amino]methyl}-3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}thiophene-2-carboxamide	KI	0.12 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[methyl(5-methyl-4,5-dihydro-1,3-oxazol-2-yl)amino]methyl}thiophene-2-carboxamide	KI	0.12 nM

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL37251
11.00	IC50	0.01	nM	CHEMBL507020
11.00	Ki	0.01	nM	CHEMBL152859
10.92	Ki	0.012	nM	CHEMBL387856
10.92	Ki	0.012	nM	CHEMBL226564
10.92	Ki	0.012	nM	CHEMBL174330
10.89	Ki	0.013	nM	CHEMBL37251
10.89	Ki	0.013	nM	CHEMBL270221
10.89	Ki	0.013	nM	CHEMBL402980
10.89	Ki	0.013	nM	CHEMBL152854
10.89	Ki	0.013	nM	CHEMBL352039
10.85	Ki	0.014	nM	CHEMBL414002
10.82	Ki	0.015	nM	CHEMBL347846
10.80	Ki	0.016	nM	CHEMBL401958
10.72	Ki	0.019	nM	CHEMBL441880
10.70	Ki	0.02	nM	CHEMBL183785
10.70	Ki	0.02	nM	CHEMBL185301
10.70	Ki	0.02	nM	CHEMBL380431
10.70	Ki	0.02	nM	CHEMBL389210
10.70	Ki	0.02	nM	CHEMBL226931
10.70	Ki	0.02	nM	CHEMBL270862
10.70	Ki	0.02	nM	CHEMBL256451
10.70	IC50	0.02	nM	CHEMBL507279
10.70	IC50	0.02	nM	CHEMBL475682
10.70	Ki	0.02	nM	CHEMBL422688
10.70	Ki	0.02	nM	CHEMBL456064
10.70	Ki	0.02	nM	CHEMBL540198
10.68	Ki	0.021	nM	CHEMBL461091
10.68	Ki	0.021	nM	CHEMBL456498
10.66	Ki	0.022	nM	CHEMBL226826
10.66	Ki	0.022	nM	CHEMBL390055
10.64	Ki	0.023	nM	CHEMBL157417
10.62	Ki	0.024	nM	CHEMBL449702
10.62	Ki	0.024	nM	CHEMBL376791
10.60	Ki	0.025	nM	CHEMBL471550
10.59	Ki	0.026	nM	CHEMBL226668
10.59	Ki	0.026	nM	CHEMBL227308
10.59	Ki	0.026	nM	CHEMBL177142
10.57	Ki	0.027	nM	CHEMBL446752
10.55	Ki	0.028	nM	CHEMBL257398
10.55	Ki	0.028	nM	CHEMBL24460
10.52	Ki	0.03	nM	CHEMBL426439
10.52	Ki	0.03	nM	CHEMBL378093
10.51	Ki	0.031	nM	CHEMBL226616
10.48	Ki	0.033	nM	CHEMBL228983
10.48	Ki	0.033	nM	CHEMBL252454
10.47	Ki	0.034	nM	CHEMBL389638
10.46	Ki	0.035	nM	CHEMBL461297
10.44	Ki	0.036	nM	CHEMBL227360
10.43	Ki	0.037	nM	CHEMBL270034

PubChem BioAssay actives

4282 with measured affinity, of 6100 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
1-(3-carbamimidoylphenyl)-N-[4-(2-sulfamoylphenyl)phenyl]tetrazole-5-carboxamide	72496: Inhibition of human purified factor Xa	ki	<0.0001	uM
2-[(6-chloronaphthalen-2-yl)sulfonyl-[(3S)-1-[2-fluoro-4-(2-oxo-1-pyridinyl)phenyl]-2-oxopiperidin-3-yl]amino]-N-[2-(dimethylamino)ethyl]-N-methylacetamide	322035: Inhibition of human factor 10a	ki	<0.0001	uM
6-chloro-N-[1-[2-fluoro-4-(2-oxo-1-pyridinyl)phenyl]-2-oxopiperidin-3-yl]thieno[2,3-b]pyridine-2-sulfonamide	322035: Inhibition of human factor 10a	ki	<0.0001	uM
1-(3-carbamimidoylphenyl)-N-[5-(2-sulfamoylphenyl)pyrimidin-2-yl]-3-(trifluoromethyl)pyrazole-5-carboxamide	51646: Binding affinity against human coagulation factor X	ki	<0.0001	uM
N-(5-chloro-2-pyridinyl)-2-[[4-(N,N-dimethylcarbamimidoyl)benzoyl]amino]benzamide	527394: Inhibition of factor 10a	ki	<0.0001	uM
5-chloro-N-(5-chloro-2-pyridinyl)-3-methoxy-2-[[4-(2-oxo-1-pyridinyl)benzoyl]amino]benzamide	331785: Inhibition of human factor 10a	ki	<0.0001	uM
2-[(6-chlorothieno[2,3-b]pyridin-2-yl)sulfonyl-[1-[2-fluoro-4-(2-oxo-1-pyridinyl)phenyl]-2-oxopiperidin-3-yl]amino]-N-methylacetamide	322035: Inhibition of human factor 10a	ki	<0.0001	uM
2-[(6-chloronaphthalen-2-yl)sulfonyl-[1-[2-fluoro-4-(2-oxo-1-pyridinyl)phenyl]-2-oxopiperidin-3-yl]amino]-N-[2-(dimethylamino)ethyl]-N-methylacetamide	322035: Inhibition of human factor 10a	ki	<0.0001	uM
2-[(6-chlorothieno[2,3-b]pyridin-2-yl)sulfonyl-[1-[2-fluoro-4-(2-oxo-1-pyridinyl)phenyl]-2-oxopiperidin-3-yl]amino]-N-[2-(dimethylamino)ethyl]-N-methylacetamide	322035: Inhibition of human factor 10a	ki	<0.0001	uM
5-chloro-N-(5-chloro-2-pyridinyl)-2-[[4-(N,N-dimethylcarbamimidoyl)benzoyl]amino]benzamide	351693: Inhibition of Factor 10a	ki	<0.0001	uM
7-[[6-(1-ethanimidoylpiperidin-4-yl)oxy-2-propan-2-ylbenzimidazol-1-yl]methyl]naphthalene-2-carboximidamide	51686: In vitro inhibitory activity against human Coagulation factor X	ki	<0.0001	uM
6-[4-[1-[(dimethylamino)methyl]cyclopropyl]phenyl]-1-(4-methoxyphenyl)-3-(trifluoromethyl)-4,5-dihydropyrazolo[5,4-c]pyridin-7-one	343864: Inhibition of human factor 10a	ki	<0.0001	uM
6-[4-[1-(diethylaminomethyl)cyclopropyl]phenyl]-1-(4-methoxyphenyl)-3-(trifluoromethyl)-4,5-dihydropyrazolo[5,4-c]pyridin-7-one	343864: Inhibition of human factor 10a	ki	<0.0001	uM
methyl 2-[(6-chlorothieno[2,3-b]pyridin-2-yl)sulfonyl-[2-oxo-1-[4-(2-oxo-1-pyridinyl)phenyl]piperidin-3-yl]amino]acetate	322035: Inhibition of human factor 10a	ki	<0.0001	uM
6-[4-[1-[(dimethylamino)methyl]cyclopropyl]phenyl]-1-(4-methoxyphenyl)-7-oxo-4,5-dihydropyrazolo[5,4-c]pyridine-3-carboxamide	396701: Binding affinity to human coagulation factor 10a	ki	<0.0001	uM
2-(3-carbamimidoylphenyl)-N-[2-fluoro-4-(2-sulfamoylphenyl)phenyl]-5-methylpyrazole-3-carboxamide	51646: Binding affinity against human coagulation factor X	ki	<0.0001	uM
2-(3-carbamimidoylphenyl)-5-methyl-N-[4-(2-methylsulfonylphenyl)phenyl]pyrazole-3-carboxamide	51646: Binding affinity against human coagulation factor X	ki	<0.0001	uM
2-(3-carbamimidoylphenyl)-5-methyl-N-[4-[2-(trifluoromethyl)phenyl]phenyl]pyrazole-3-carboxamide	51646: Binding affinity against human coagulation factor X	ki	<0.0001	uM
1-(3-carbamimidoylphenyl)-N-[4-(2-methylsulfonylphenyl)phenyl]-3-(trifluoromethyl)pyrazole-5-carboxamide	51646: Binding affinity against human coagulation factor X	ki	<0.0001	uM
2-(3-carbamimidoylphenyl)-5-methyl-N-[5-(2-sulfamoylphenyl)-2-pyridinyl]pyrazole-3-carboxamide	51646: Binding affinity against human coagulation factor X	ki	<0.0001	uM
N-[2-bromo-4-(2-sulfamoylphenyl)phenyl]-2-(3-carbamimidoylphenyl)-5-methylpyrazole-3-carboxamide	51646: Binding affinity against human coagulation factor X	ki	<0.0001	uM
3-[[(3R)-3-[(7-methoxynaphthalen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]benzenecarboximidamide	52156: Compound was evaluated for the inhibition of human Coagulation factor Xa	ki	<0.0001	uM
2-(3-carbamimidoylphenyl)-N-[2-chloro-4-(2-sulfamoylphenyl)phenyl]-5-methylpyrazole-3-carboxamide	51646: Binding affinity against human coagulation factor X	ki	<0.0001	uM
2-(3-carbamimidoylphenyl)-N-[2-fluoro-4-(2-methylsulfonylphenyl)phenyl]-5-methylpyrazole-3-carboxamide	51646: Binding affinity against human coagulation factor X	ki	<0.0001	uM
1-[4-[2-[1-(3-amino-1,2-benzoxazol-5-yl)-3-(trifluoromethyl)pyrazol-5-yl]-2-oxoethyl]-3-fluorophenyl]pyridin-2-one	313675: Inhibition of human factor 10a	ki	<0.0001	uM
N-(5-chloro-2-pyridinyl)-5-methyl-2-[[4-(2-oxo-1-pyridinyl)benzoyl]amino]benzamide	331785: Inhibition of human factor 10a	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[(2-imino-4-oxoimidazolidin-1-yl)methyl]thiophene-2-carboxamide	290948: Inhibition of human F10a	ki	<0.0001	uM
1-(3-carbamimidoylphenyl)-N-[4-(2-sulfamoylphenyl)phenyl]-3-(trifluoromethyl)pyrazole-5-carboxamide	51646: Binding affinity against human coagulation factor X	ki	<0.0001	uM
(2R)-N-[(2S)-1-[[2-(aminomethyl)-5-chlorophenyl]methylamino]-1-oxopropan-2-yl]-2-(benzylsulfonylamino)-4-(1-oxidopyridin-1-ium-2-yl)butanamide	290688: Inhibition of factor 10a	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[[3-(dimethylamino)propyl-methylamino]methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[[methyl(2-pyrrolidin-1-ylethyl)amino]methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[[methyl(methylsulfonyl)amino]methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
4-[[carbamoyl(methyl)amino]methyl]-3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[[ethylcarbamoyl(methyl)amino]methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[[methyl(2-pyrrolidin-1-ylethylcarbamoyl)amino]methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-[[[4-chloro-5-[[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]carbamoyl]thiophen-3-yl]methyl-methylcarbamoyl]amino]propanoic acid	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[[4,5-dihydro-1,3-oxazol-2-yl(ethyl)amino]methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[[ethyl-(4-methyl-4,5-dihydro-1,3-oxazol-2-yl)amino]methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[[5,6-dihydro-4H-1,3-oxazin-2-yl(methyl)amino]methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[[methyl-(4-oxo-1,3-oxazol-2-yl)amino]methyl]thiophene-2-carboxamide	290948: Inhibition of human F10a	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[[4,5-dihydro-1,3-thiazol-2-yl(methyl)amino]methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[[3,4-dihydro-2H-pyrrol-5-yl(methyl)amino]methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[(2-imino-1,3-oxazolidin-3-yl)methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[(2-imino-1,3-thiazolidin-3-yl)methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
4-[(2-amino-4,5-dihydroimidazol-1-yl)methyl]-3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[(2-methylsulfanyl-4,5-dihydroimidazol-1-yl)methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[(2-methyl-4,5-dihydroimidazol-1-yl)methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-(4,5-dihydroimidazol-1-ylmethyl)thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[[ethanimidoyl(methyl)amino]methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
4-[[carbamimidoyl(methyl)amino]methyl]-3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases expression	4
Cyclosporine	decreases expression	3
Aflatoxin B1	increases methylation, affects expression, decreases expression	3
Contraceptives, Oral	increases activity, increases expression	2
Ethinyl Estradiol	increases expression, affects activity, affects cotreatment, affects binding	2
Snake Venoms	decreases activity, increases activity	2
Viper Venoms	decreases activity, increases activity, affects binding	2
dicrotophos	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	affects expression	1
kojic acid	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
mangiferin	decreases activity	1
beta-lapachone	decreases expression, increases expression	1
4-chloro-1,2-diaminobenzene	affects response to substance	1
sodium arsenite	decreases expression	1
ferrous sulfate	decreases activity	1
perfluorooctanoic acid	decreases expression	1
ferric citrate	decreases activity	1
Gestodene	affects activity, affects cotreatment	1
micrurus venom	affects reaction, decreases activity, decreases reaction	1
2,3-dimethoxy-1,4-naphthoquinone	decreases expression	1
(2S)-2-(4-(((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy)phenyl)-3-(7-amidino-2-naphtyl)propanoic acid	decreases activity	1
reviparin	decreases activity	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
varespladib	decreases activity, decreases reaction	1
estradiol, norethindrone drug combination	decreases expression	1
2-(3-bromo-2-hydroxy-5-methylphenyl)-1H-indole-5-carboxamidine	affects binding, decreases activity	1
2-(2-hydroxybiphenyl-3-yl)-1H-indole-5-carboxamidine	affects binding, decreases activity	1

ChEMBL screening assays

795 unique, capped per target: 779 binding, 9 functional, 7 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL832226	Binding	Ki ratio of human alpha thrombin to activated factor X	In-depth study of tripeptide-based alpha-ketoheterocycles as inhibitors of thrombin. Effective utilization of the S1’ subsite and its implications to structure-based drug design. — J Med Chem
CHEMBL883177	Functional	Anticoagulant potency against double prothrombin time	Investigation of factor Xa inhibitors containing non-amidine S1 elements. — Bioorg Med Chem Lett
CHEMBL4305262	ADMET	Inhibition of factor 10a (unknown origin) using spectrozyme 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)

244 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
NCT00930176	PHASE3	COMPLETED	A Study Investigating Treatment Factor X in People With Factor X Deficiency
NCT01086852	PHASE3	TERMINATED	Safety & Efficacy of BPL’s High Purity FACTOR X in Treatment of Factor X Deficient Subjects Undergoing Surgery
NCT01721681	PHASE3	COMPLETED	A Study to Investigate Bio Product Laboratory Ltd (BPL’s) Factor X in the Prophylaxis of Bleeding in Children <12 Years
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