Berotralstat

Summary

Berotralstat (CHEMBL5189739) is an approved small molecule (ATC B06AC06) targeting KLKB1; indicated across 2 conditions including hereditary angioedema and angioedema.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: B06AC06
• Targets: 1 (KLKB1)
• Indications: 2 conditions
• Clinical trials: 12
• Chemistry: 562.6 Da · C30H26F4N6O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL5189739
Name	Berotralstat
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	137528262
ATC	B06AC06
Molecular formula	C30H26F4N6O
Molecular weight	562.6
InChIKey	UXNXMBYCBRBRFD-MUUNZHRXSA-N

SMILES: C1CC1CN[C@@H](C2=CC(=C(C=C2)F)NC(=O)C3=CC(=NN3C4=CC=CC(=C4)CN)C(F)(F)F)C5=CC=CC(=C5)C#N

IUPAC name: 1-[3-(aminomethyl)phenyl]-N-[5-[(R)-(3-cyanophenyl)-(cyclopropylmethylamino)methyl]-2-fluorophenyl]-3-(trifluoromethyl)pyrazole-5-carboxamide

Also known as: BCX-7353, Bcx7353, BCX7353, Berotralstat, BEROTRALSTAT

Parent form; salt/anhydrous children: CHEMBL6067995

Patent coverage: 2 distinct patent families (7 SureChEMBL compound mentions), from 1 matched compound structure(s). 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
KLKB1	kallikrein B1	Inhibition	10	0%	P03952

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Plasminogen, Plasma kallikrein, Trypsin.

Bioactivity

ChEMBL activities: 15 potent at pChembl ≥ 5 of 16 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
KLKB1	9.36	Ki	0.44	nM	CHEMBL_ACT_23312842
KLKB1	9.06	IC50	0.88	nM	CHEMBL_ACT_23312761
KLKB1	9	IC50	1	nM	CHEMBL_ACT_24872427
KLKB1	8.74	IC50	1.8	nM	CHEMBL_ACT_23312760
KLKB1	8.24	IC50	5.8	nM	CHEMBL_ACT_23312778
KLKB1	7.86	IC50	13.9	nM	CHEMBL_ACT_23312762
KLKB1	7.85	IC50	14	nM	CHEMBL_ACT_23312777
KLKB1	7.6	Ki	25.1	nM	CHEMBL_ACT_27773405
KLKB1	7.6	Ki	25.1	nM	CHEMBL_ACT_27773510
KLKB1	7.6	Ki	25.1	nM	CHEMBL_ACT_27773519
KLKB1	7.6	Ki	25.1	nM	CHEMBL_ACT_29028023
KLKB1	7.6	Ki	25.1	nM	CHEMBL_ACT_29028128
KLKB1	7.6	Ki	25.1	nM	CHEMBL_ACT_29028137
KLKB1	7.32	IC50	48.1	nM	CHEMBL_ACT_23312779
PLG	5.4	IC50	3967	nM	CHEMBL_ACT_23312803

Target pathways

Aggregated over 1 target gene(s): KLKB1.

Top Reactome pathways

14 total, by targets touching each:

Pathway	Targets	Genes
Hemostasis	1	KLKB1
R-HSA-140837	1	KLKB1
R-HSA-140877	1	KLKB1
Degradation of the extracellular matrix	1	KLKB1
Extracellular matrix organization	1	KLKB1
Activation of Matrix Metalloproteinases	1	KLKB1
Disease	1	KLKB1
R-HSA-9651496	1	KLKB1
Defective factor XII causes hereditary angioedema	1	KLKB1
Defective SERPING1 causes hereditary angioedema	1	KLKB1
Diseases of hemostasis	1	KLKB1
Regulation of FXIIa and plasma kallikrein activity	1	KLKB1
FXIIa, PKa-dependent activation of coagulation pathway	1	KLKB1
FXIIa activates plasma kallikrein-kinin system	1	KLKB1

Dominant GO biological processes

GO term	Targets
Factor XII activation	1
proteolysis	1
blood coagulation	1
zymogen activation	1
plasminogen activation	1
fibrinolysis	1
positive regulation of fibrinolysis	1
inflammatory response	1
hemostasis	1

Indications & clinical

Indications

2 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
hereditary angioedema	4	MONDO:0019623	MONDO:0019623
angioedema	1	MONDO:0010481	EFO:0005532

Clinical trials

Total trials: 12.

Phase distribution

Phase	Trials
PHASE3	4
PHASE1	4
PHASE2	2
PHASE2/PHASE3	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04933721	PHASE3	ENROLLING_BY_INVITATION	Open-label Berotralstat Access to HAE Patients Previously Enrolled in Berotralstat Studies
NCT05453968	PHASE3	ACTIVE_NOT_RECRUITING	Berotralstat Treatment in Children With Hereditary Angioedema
NCT03472040	PHASE2/PHASE3	COMPLETED	A Long Term Safety Study of BCX7353 in Hereditary Angioedema
NCT03485911	PHASE3	COMPLETED	Efficacy and Safety Study of BCX7353 as an Oral Treatment for the Prevention of Attacks in HAE
NCT03873116	PHASE3	COMPLETED	Study to Evaluate the Efficacy and Safety of BCX7353 as an Oral Treatment for the Prevention of HAE Attacks in Japan
NCT02870972	PHASE2	COMPLETED	Efficacy and Safety of BCX7353 to Prevent Angioedema Attacks in Subjects With Hereditary Angioedema
NCT03240133	PHASE2	COMPLETED	Study of BCX7353 as a Treatment for Attacks of Hereditary Angioedema
NCT02448264	PHASE1	COMPLETED	First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BCX7353 in Healthy Western and Japanese Volunteers
NCT02819102	PHASE1	COMPLETED	An Open-label Drug-Drug Interaction Study to Evaluate the Effect of BCX7353 on Cytochrome P450 Enzyme Activity Using Probe Substrates
NCT03136237	PHASE1	COMPLETED	A Drug-Drug Interaction Study to Evaluate Drug Transporter Interactions
NCT03202784	PHASE1	COMPLETED	A Relative Bioavailability Study of Two Formulations of BCX7353
NCT04428632	Not specified	APPROVED_FOR_MARKETING	Oral Berotralstat Expanded Access Program

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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.

9 molecules share ≥1 primary target. Top 9 by shared-target count:

Molecule	Source	Status	Shared targets
AVORALSTAT	ChEMBL	Phase 3	KLKB1
DAREXABAN	ChEMBL	Phase 3	KLKB1
GABEXATE	ChEMBL	Phase 3	KLKB1
MILVEXIAN	ChEMBL	Phase 3	KLKB1
SEBETRALSTAT	ChEMBL	Phase 3	KLKB1
FENIRALSTAT	ChEMBL	Phase 2	KLKB1
GW813893	ChEMBL	Phase 2	KLKB1
LETAXABAN	ChEMBL	Phase 2	KLKB1
Amiloride	PubChem	Approved	KLKB1