berotralstat 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
enzyme inhibitors	5430	1809010-50-1

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: berotralstat berotralstat hydrochloride BCX7353 orladeyo	Berotralstat is a plasma kallikrein inhibitor that binds to plasma kallikrein and inhibits its proteolytic activity. Plasma kallikrein is a protease that cleaves high-molecular-weight-kininogen (HMWK) to generate cleaved HMWK (cHMWK) and bradykinin, a potent vasodilator that increases vascular permeability resulting in swelling and pain associated with HAE. In patients with HAE due to C1-inhibitor (C1-INH) deficiency or dysfunction, normal regulation of plasma kallikrein activity is not present, which leads to uncontrolled increases in plasma kallikrein activity and results in angioedema attacks. Berotralstat decreases plasma kallikrein activity to control excess bradykinin generation in patients with HAE. Molecular weight: 562.57 Formula: C30H26F4N6O CLOGP: 3.84 LIPINSKI: 2 HAC: 7 HDO: 3 TPSA: 108.76 ALOGS: -5.37 ROTB: 10 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

berotralstat
berotralstat hydrochloride
BCX7353
orladeyo

Berotralstat is a plasma kallikrein inhibitor that binds to plasma kallikrein and inhibits its proteolytic activity. Plasma kallikrein is a protease that cleaves high-molecular-weight-kininogen (HMWK) to generate cleaved HMWK (cHMWK) and bradykinin, a potent vasodilator that increases vascular permeability resulting in swelling and pain associated with HAE. In patients with HAE due to C1-inhibitor (C1-INH) deficiency or dysfunction, normal regulation of plasma kallikrein activity is not present, which leads to uncontrolled increases in plasma kallikrein activity and results in angioedema attacks. Berotralstat decreases plasma kallikrein activity to control excess bradykinin generation in patients with HAE.

Molecular weight: 562.57
Formula: C30H26F4N6O
CLOGP: 3.84
LIPINSKI: 2
HAC: 7
HDO: 3
TPSA: 108.76
ALOGS: -5.37
ROTB: 10

Status: ONP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
0.15	g	O

ADMET properties:

Property	Value	Reference
S (Water solubility)	1.09 mg/mL	Bocci G, Oprea TI, Benet LZ
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Bocci G, Oprea TI, Benet LZ

Approvals:

Date	Agency	Company
April 30, 2021	EMA	BioCryst Ireland Limited
Dec. 3, 2020	FDA	BIOCRYST
Jan. 22, 2021	PMDA	ORPHAN PACIFIC, Inc

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Hereditary angioedema	79.10	49.53	12	45	7550	63481415

FDA Adverse Event Reporting System (Male)

None

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Hereditary angioedema	81.87	43.20	12	66	5323	79738987

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	B06AC06	BLOOD AND BLOOD FORMING ORGANS OTHER HEMATOLOGICAL AGENTS OTHER HEMATOLOGICAL AGENTS Drugs used in hereditary angioedema
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D011480	Protease Inhibitors
MeSH PA	D015842	Serine Proteinase Inhibitors
FDA MoA	N0000182137	Cytochrome P450 2D6 Inhibitors
FDA MoA	N0000182141	Cytochrome P450 3A4 Inhibitors
FDA MoA	N0000184151	Kallikrein Inhibitors
FDA MoA	N0000185503	P-Glycoprotein Inhibitors
FDA EPC	N0000192750	Plasma Kallikrein Inhibitor

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
Hereditary angioneurotic edema	indication	82966003	DOID:14735

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent use
EQ 110MG BASE	ORLADEYO	BIOCRYST	N214094	Dec. 3, 2020	RX	CAPSULE	ORAL	10689346	March 9, 2035	PROPHYLAXIS TO PREVENT ATTACKS OF HEREDITARY ANGIOEDEMA (HAE) IN ADULTS AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER
EQ 110MG BASE	ORLADEYO	BIOCRYST	N214094	Dec. 3, 2020	RX	CAPSULE	ORAL	11230530	March 9, 2035	PROPHYLAXIS TO PREVENT ATTACKS OF HEREDITARY ANGIOEDEMA (HAE) IN ADULTS AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER
EQ 150MG BASE	ORLADEYO	BIOCRYST	N214094	Dec. 3, 2020	RX	CAPSULE	ORAL	10689346	March 9, 2035	PROPHYLAXIS TO PREVENT ATTACKS OF HEREDITARY ANGIOEDEMA (HAE) IN ADULTS AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER
EQ 150MG BASE	ORLADEYO	BIOCRYST	N214094	Dec. 3, 2020	RX	CAPSULE	ORAL	11230530	March 9, 2035	PROPHYLAXIS TO PREVENT ATTACKS OF HEREDITARY ANGIOEDEMA (HAE) IN ADULTS AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER
EQ 110MG BASE	ORLADEYO	BIOCRYST	N214094	Dec. 3, 2020	RX	CAPSULE	ORAL	10125102	April 7, 2035	PROPHYLAXIS TO PREVENT ATTACKS OF HEREDITARY ANGIOEDEMA (HAE) IN ADULTS AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER
EQ 150MG BASE	ORLADEYO	BIOCRYST	N214094	Dec. 3, 2020	RX	CAPSULE	ORAL	10125102	April 7, 2035	PROPHYLAXIS TO PREVENT ATTACKS OF HEREDITARY ANGIOEDEMA (HAE) IN ADULTS AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER
EQ 110MG BASE	ORLADEYO	BIOCRYST	N214094	Dec. 3, 2020	RX	CAPSULE	ORAL	10662160	Nov. 1, 2039	PROPHYLAXIS TO PREVENT ATTACKS OF HEREDITARY ANGIOEDEMA (HAE) IN ADULTS AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER
EQ 110MG BASE	ORLADEYO	BIOCRYST	N214094	Dec. 3, 2020	RX	CAPSULE	ORAL	11117867	Nov. 1, 2039	PROPHYLAXIS TO PREVENT ATTACKS OF HEREDITARY ANGIOEDEMA (HAE) IN ADULTS AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER
EQ 110MG BASE	ORLADEYO	BIOCRYST	N214094	Dec. 3, 2020	RX	CAPSULE	ORAL	11618733	Nov. 1, 2039	PROPHYLAXIS TO PREVENT ATTACKS OF HEREDITARY ANGIOEDEMA (HAE) IN ADULTS AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER
EQ 150MG BASE	ORLADEYO	BIOCRYST	N214094	Dec. 3, 2020	RX	CAPSULE	ORAL	10662160	Nov. 1, 2039	PROPHYLAXIS TO PREVENT ATTACKS OF HEREDITARY ANGIOEDEMA (HAE) IN ADULTS AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER
EQ 150MG BASE	ORLADEYO	BIOCRYST	N214094	Dec. 3, 2020	RX	CAPSULE	ORAL	11117867	Nov. 1, 2039	PROPHYLAXIS TO PREVENT ATTACKS OF HEREDITARY ANGIOEDEMA (HAE) IN ADULTS AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER
EQ 150MG BASE	ORLADEYO	BIOCRYST	N214094	Dec. 3, 2020	RX	CAPSULE	ORAL	11618733	Nov. 1, 2039	PROPHYLAXIS TO PREVENT ATTACKS OF HEREDITARY ANGIOEDEMA (HAE) IN ADULTS AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
EQ 110MG BASE	ORLADEYO	BIOCRYST	N214094	Dec. 3, 2020	RX	CAPSULE	ORAL	Dec. 3, 2025	NEW CHEMICAL ENTITY
EQ 150MG BASE	ORLADEYO	BIOCRYST	N214094	Dec. 3, 2020	RX	CAPSULE	ORAL	Dec. 3, 2025	NEW CHEMICAL ENTITY
EQ 110MG BASE	ORLADEYO	BIOCRYST	N214094	Dec. 3, 2020	RX	CAPSULE	ORAL	Dec. 3, 2027	PROPHYLAXIS TO PREVENT ATTACKS OF HEREDITARY ANGIOEDEMA (HAE) IN ADULTS AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER
EQ 150MG BASE	ORLADEYO	BIOCRYST	N214094	Dec. 3, 2020	RX	CAPSULE	ORAL	Dec. 3, 2027	PROPHYLAXIS TO PREVENT ATTACKS OF HEREDITARY ANGIOEDEMA (HAE) IN ADULTS AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Plasma kallikrein	Enzyme	P03952	KLKB1_HUMAN	INHIBITOR	IC50	7.80		DRUG LABEL	DRUG LABEL
Plasminogen	Enzyme	P00747	PLMN_HUMAN		IC50	5.40		CHEMBL

External reference:

ID	Source
D11673	KEGG_DRUG
XZA0KB1BDQ	UNII
1809010-52-3	SECONDARY_CAS_RN
C5392453	UMLSCUI
0RI	PDB_CHEM_ID
CHEMBL4594271	ChEMBL_ID
137528262	PUBCHEM_CID
DB15982	DRUGBANK_ID
CHEMBL4594272	ChEMBL_ID
11347	IUPHAR_LIGAND_ID
018585	NDDF
018586	NDDF
1144607003	SNOMEDCT_US
1144608008	SNOMEDCT_US
1144618003	SNOMEDCT_US
4039913	VANDF
4039915	VANDF
2467540	RXNORM
341763	MMSL
39091	MMSL
d09694	MMSL
C000706836	MESH_SUPPLEMENTAL_RECORD_UI
10907	INN_ID

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Orladeyo	HUMAN PRESCRIPTION DRUG LABEL	1	72769-101	CAPSULE	150 mg	ORAL	NDA	29 sections
Orladeyo	HUMAN PRESCRIPTION DRUG LABEL	1	72769-101	CAPSULE	150 mg	ORAL	NDA	29 sections
Orladeyo	HUMAN PRESCRIPTION DRUG LABEL	1	72769-102	CAPSULE	110 mg	ORAL	NDA	29 sections
Orladeyo	HUMAN PRESCRIPTION DRUG LABEL	1	72769-102	CAPSULE	110 mg	ORAL	NDA	29 sections