Betrixaban

Summary

Betrixaban (CHEMBL512351) is an approved small-molecule anticoagulant (ATC B01AF04) targeting F10; indicated across 8 conditions including venous thromboembolism and thrombotic disease.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: B01AF04
• Targets: 1 (F10)
• Indications: 8 conditions
• Clinical trials: 9
• Chemistry: 451.9 Da · C23H22ClN5O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL512351
Name	Betrixaban
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	10275777
ChEBI	CHEBI:140421
ATC	B01AF04
Molecular formula	C23H22ClN5O3
Molecular weight	451.9
InChIKey	XHOLNRLADUSQLD-UHFFFAOYSA-N

SMILES: CN(C)C(=N)C1=CC=C(C=C1)C(=O)NC2=C(C=C(C=C2)OC)C(=O)NC3=NC=C(C=C3)Cl

IUPAC name: N-(5-chloro-2-pyridinyl)-2-[[4-(N,N-dimethylcarbamimidoyl)benzoyl]amino]-5-methoxybenzamide

ChEBI definition: A secondary carboxamide obtained by formal condensation of the carboxy group of 4-(N,N-dimethylcarbamimidoyl)benzoic acid with the amino group of 2-amino-N-(5-chloropyridin-2-yl)-5-methoxybenzamide. A synthetic anticoagulant compound that targets activated factor Xa in the coagulation cascade.

Pharmacological roles (ChEBI): anticoagulant, EC 3.4.21.6 (coagulation factor Xa) inhibitor.

Also known as: Betrixaban, Betrixaban maleate, Bevyxxa, PRT-054021, PRT054021, BETRIXABAN

Patent coverage: 433 distinct patent families (1,084 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 867 (80%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
F10	coagulation factor X	Inhibition	9.93	0%	P00742

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Prothrombin, Voltage-gated inwardly rectifying potassium channel KCNH2, Coagulation factor X.

Bioactivity

ChEMBL activities: 9 potent at pChembl ≥ 5 of 11 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
F10	9.93	Ki	0.12	nM	CHEMBL_ACT_2517466
F10	9.92	Ki	0.12	nM	CHEMBL_ACT_3515048
F10	8.82	IC50	1.5	nM	CHEMBL_ACT_2516591
F10	8.35	IC50	4.5	nM	CHEMBL_ACT_18191570
F10	8.35	IC50	4.5	nM	CHEMBL_ACT_19163742
F2	7.75	IC50	18	nM	CHEMBL_ACT_19163759
KCNH2	5.75	Ki	1800	nM	CHEMBL_ACT_2516658
KCNH2	5.05	IC50	8900	nM	CHEMBL_ACT_2516667
KCNH2	5.05	IC50	8900	nM	CHEMBL_ACT_3515195

Target pathways

Aggregated over 1 target gene(s): F10.

Top Reactome pathways

12 total, by targets touching each:

Pathway	Targets	Genes
R-HSA-140834	1	F10
R-HSA-140837	1	F10
R-HSA-140875	1	F10
Gamma-carboxylation of protein precursors	1	F10
Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus	1	F10
Removal of aminoterminal propeptides from gamma-carboxylated proteins	1	F10
Defective factor IX causes thrombophilia	1	F10
Defective cofactor function of FVIIIa variant	1	F10
Defective F9 variant does not activate FX	1	F10
Initiation of coagulation cascade	1	F10
Regulation of clotting cascade	1	F10
Amplification and propagation of coagulation cascade	1	F10

Dominant GO biological processes

GO term	Targets
proteolysis	1
blood coagulation	1
positive regulation of cell migration	1
positive regulation of TOR signaling	1
hemostasis	1

Indications & clinical

Indications

2 approved indications. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

Indication	Phase	MONDO	EFO
venous thromboembolism	4	MONDO:0005399	EFO:0004286
thrombotic disease	4	MONDO:0000831	HP:0004419

4 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
atrial fibrillation	2	MONDO:0004981	EFO:0000275
atrial flutter	2	MONDO:0005310	EFO:0003911
liver disorder	1	MONDO:0005154	EFO:0001421
kidney disorder	1	MONDO:0005240	EFO:0003086

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 9.

Phase distribution

Phase	Trials
PHASE1	5
PHASE2	3
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01583218	PHASE3	COMPLETED	Acute Medically Ill VTE Prevention With Extended Duration Betrixaban Study (The APEX Study)
NCT00375609	PHASE2	COMPLETED	Factor Xa Inhibitor, PRT054021, Against Enoxaparin for the Prevention of Venous Thromboembolic Events (EXPERT)
NCT00742859	PHASE2	COMPLETED	Phase 2 Study of the Safety, Tolerability and Pilot Efficacy of Oral Factor Xa Inhibitor Betrixaban Compared to Warfarin
NCT01229254	PHASE2	COMPLETED	Evaluate the Pharmacokinetics and Safety of MK-4448 in Participants With Nonvalvular Atrial Fibrillation or Atrial Flutter
NCT00999336	PHASE1	COMPLETED	A Study to Determine the Pharmacokinetics, Pharmacodynamics, and Tolerabiltiy of Betrixaban in Patients With Mild, Moderate, and Severe Renal Impairment
NCT01765868	PHASE1	COMPLETED	A Human Phase I Absolute Bioavailability Study of PRT054021 in Healthy Male Volunteers
NCT02596100	PHASE1	COMPLETED	A Bioequivalence Study to Compare the Pharmacokinetics of Two Betrixaban Formulations
NCT03346083	PHASE1	TERMINATED	Study Evaluating Betrixaban in Pediatric Participants
NCT03397888	PHASE1	COMPLETED	The Effect o f Hepatic Impairment on the Pharmacokinetics and Pharmacodynamics of Betrixiban, an Oral FXa Antagonist

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

21 molecules share ≥1 primary target. Top 21 by shared-target count:

Molecule	Source	Status	Shared targets
APIXABAN	ChEMBL + PubChem	Phase 4 (approved)	F10
EDOXABAN	ChEMBL + PubChem	Phase 4 (approved)	F10
ARGATROBAN	ChEMBL	Phase 4 (approved)	F10
FONDAPARINUX	ChEMBL	Phase 4 (approved)	F10
MELAGATRAN	ChEMBL	Phase 4 (approved)	F10
PENTAMIDINE	ChEMBL	Phase 4 (approved)	F10
RIVAROXABAN	ChEMBL	Phase 4 (approved)	F10
DABIGATRAN	ChEMBL	Phase 3	F10
DAREXABAN	ChEMBL	Phase 3	F10
GABEXATE	ChEMBL	Phase 3	F10
NAFAMOSTAT	ChEMBL	Phase 3	F10
OTAMIXABAN	ChEMBL	Phase 3	F10
EFEGATRAN	ChEMBL	Phase 2	F10
ERIBAXABAN	ChEMBL	Phase 2	F10
FIDEXABAN	ChEMBL	Phase 2	F10
GW813893	ChEMBL	Phase 2	F10
LETAXABAN	ChEMBL	Phase 2	F10
LY-517717	ChEMBL	Phase 2	F10
RAZAXABAN	ChEMBL	Phase 2	F10
SEGATROXABAN	ChEMBL	Phase 2	F10
TANOGITRAN	ChEMBL	Phase 2	F10