Sebetralstat

Summary

Sebetralstat (CHEMBL5095248) is a phase-3 clinical-stage small molecule (ATC B06AC08) targeting KLKB1; indicated across 2 conditions including hereditary angioedema and angioedema.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• ATC class: B06AC08
• Targets: 1 (KLKB1)
• Indications: 2 conditions
• Clinical trials: 8
• Chemistry: 491.5 Da · C26H26FN5O4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL5095248
Name	Sebetralstat
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	121365142
ATC	B06AC08
Molecular formula	C26H26FN5O4
Molecular weight	491.5
InChIKey	KGMPDQIYDKKXRD-UHFFFAOYSA-N

SMILES: COCC1=NN(C=C1C(=O)NCC2=NC=CC(=C2F)OC)CC3=CC=C(C=C3)CN4C=CC=CC4=O

IUPAC name: N-[(3-fluoro-4-methoxy-2-pyridinyl)methyl]-3-(methoxymethyl)-1-[[4-[(2-oxo-1-pyridinyl)methyl]phenyl]methyl]pyrazole-4-carboxamide

Also known as: KVD-900, KVD900, Sebetralstat, SEBETRALSTAT

Patent coverage: 30 distinct patent families (102 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 74 (73%) 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
KLKB1	kallikrein B1	Inhibition	8.22	0%	P03952

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Plasma kallikrein.

Bioactivity

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

Target	pChembl	Type	Value	Unit	Activity ID
KLKB1	8.52	Ki	3	nM	CHEMBL_ACT_24721277
KLKB1	8.48	IC50	3.3	nM	CHEMBL_ACT_27717278
KLKB1	8.48	IC50	3.3	nM	CHEMBL_ACT_28341737
KLKB1	8.48	IC50	3.3	nM	CHEMBL_ACT_28445081
KLKB1	8.48	IC50	3.3	nM	CHEMBL_ACT_28556939
KLKB1	8.48	IC50	3.3	nM	CHEMBL_ACT_28563401
KLKB1	8.48	IC50	3.3	nM	CHEMBL_ACT_28948067
KLKB1	8.22	IC50	6	nM	CHEMBL_ACT_24721069
KLKB1	7.27	IC50	54	nM	CHEMBL_ACT_24721247
KLKB1	7.26	EC50	55	nM	CHEMBL_ACT_28717793

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 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
hereditary angioedema	3	MONDO:0019623	MONDO:0019623
angioedema	1	MONDO:0010481	EFO:0005532

Clinical trials

Total trials: 8.

Phase distribution

Phase	Trials
PHASE3	4
Not specified	2
PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05505916	PHASE3	ACTIVE_NOT_RECRUITING	An Open-label Extension Trial to Evaluate the Long-term Safety of KVD900 (Sebetralstat) for On-Demand Treatment of Angioedema Attacks in Adolescent and Adult Patients With Hereditary Angioedema (HAE)
NCT05511922	PHASE3	ACTIVE_NOT_RECRUITING	PK Subtrial in Adolescent Patients With HAE Type I or II Participating in the KVD900-302 Trial
NCT05259917	PHASE3	COMPLETED	A Phase III, Crossover Trial Evaluating the Efficacy and Safety of KVD900 (Sebetralstat) for On-Demand Treatment of Angioedema Attacks in Adolescent and Adult Patients With Hereditary Angioedema (HAE)
NCT06467084	PHASE3	COMPLETED	Open-Label Safety, PK, and Efficacy Trial of Sebetralstat (KVD900) in Pediatric Patients (Ages 2-11) With HAE Type I or II
NCT04208412	PHASE2	COMPLETED	A Phase II, Cross-over Clinical Trial Evaluating the Efficacy and Safety of KVD900 (Sebetralstat) in the On-demand Treatment of Angioedema Attacks in Adult Subjects With Hereditary Angioedema Type I or II
NCT04349800	PHASE1	COMPLETED	A Single Dose Safety, Tolerability, Pharmacokinetic and Food Effect Study of KVD900 (Sebetralstat) in Healthy Volunteers
NCT07216378	Not specified	AVAILABLE	Treatment of Angioedema Attacks in Pediatric (Ages 2-11) Post-Trial and Naive Patients With HAE With Sebetralstat
NCT06628713	Not specified	APPROVED_FOR_MARKETING	Treatment of Angioedema Attacks in Adolescent and Adult Patients 12 Years and Older With HAE Type I or II With Sebetralstat

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
BEROTRALSTAT	ChEMBL + PubChem	Phase 4 (approved)	KLKB1
AVORALSTAT	ChEMBL	Phase 3	KLKB1
DAREXABAN	ChEMBL	Phase 3	KLKB1
GABEXATE	ChEMBL	Phase 3	KLKB1
MILVEXIAN	ChEMBL	Phase 3	KLKB1
FENIRALSTAT	ChEMBL	Phase 2	KLKB1
GW813893	ChEMBL	Phase 2	KLKB1
LETAXABAN	ChEMBL	Phase 2	KLKB1
Amiloride	PubChem	Approved	KLKB1