berotralstat 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
enzyme inhibitors 5430 1809010-50-1

Description:

MoleculeDescription

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:

DoseUnitRoute
0.15 g O

ADMET properties:

PropertyValueReference
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

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
kinase-safety-class AKT3,AXL,BRAF,CAMK2B,CAMK2D,CDK5,EGFR,EIF2AK3,ERBB2,GRK2,INSR,ITK,MAPK10,MET,NTRK2,PDK1,PDK2,PDK4 18
kinase-selectivity-class EIF2AK3,PDK4 2
pfas-class PFAS structural alert (1 = True, 0 = False) 1

Approvals:

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

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hereditary angioedema 187.00 40.17 30 195 9335 90618887

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hereditary angioedema 65.83 52.96 9 59 1472 42619795

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hereditary angioedema 176.08 42.06 27 214 7087 110581971

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
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

Related Drugs by ATC class:

B06AC Drugs used in hereditary angioedema 7 drugs
conestat alfadonidalorsenecallantidegaradacimabicatibantlanadelumabsebetralstat

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

DiseaseRelationSNOMED_IDDOID
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 strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent 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 ADULT 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 110MG BASE ORLADEYO BIOCRYST N214094 Dec. 3, 2020 RX CAPSULE ORAL 11708333 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 ADULT 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 ADULT 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 ADULT 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 110MG BASE ORLADEYO BIOCRYST N214094 Dec. 3, 2020 RX CAPSULE ORAL 12344585 Nov. 1, 2039 PROPHYLAXIS TO PREVENT ATTACKS OF HEREDITARY ANGIOEDEMA (HAE) IN ADULT AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
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 110MG BASE ORLADEYO BIOCRYST N214094 Dec. 3, 2020 RX CAPSULE ORAL June 3, 2028 PEDIATRIC EXCLUSIVITY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Plasma kallikrein Enzyme INHIBITOR IC50 7.80 DRUG LABEL DRUG LABEL
Plasminogen Enzyme IC50 5.40 CHEMBL

External reference:

IDSource
D11673 KEGG_DRUG
XZA0KB1BDQ UNII
1809010-52-3 SECONDARY_CAS_RN
C5392453 UMLSCUI
CHEBI:759066 CHEBI
0RI PDB_CHEM_ID
CHEMBL5189739 ChEMBL_ID
137528262 PUBCHEM_CID
DB15982 DRUGBANK_ID
CHEMBL6067995 ChEMBL_ID
10907 INN_ID
C000706836 MESH_SUPPLEMENTAL_RECORD_UI
11347 IUPHAR_LIGAND_ID
1144607003 SNOMEDCT_US
1144608008 SNOMEDCT_US
1144618003 SNOMEDCT_US
4039913 VANDF
4039915 VANDF
341763 MMSL
39091 MMSL
d09694 MMSL
018585 NDDF
018586 NDDF
2467540 RXNORM
XZA0KB1BDQ INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Orladeyo HUMAN PRESCRIPTION DRUG LABEL 1 72769-101 CAPSULE 150 mg ORAL NDA 31 sections
Orladeyo HUMAN PRESCRIPTION DRUG LABEL 1 72769-102 CAPSULE 110 mg ORAL NDA 31 sections
Orladeyo HUMAN PRESCRIPTION DRUG LABEL 1 72769-111 PELLET 72 mg ORAL NDA 31 sections
Orladeyo HUMAN PRESCRIPTION DRUG LABEL 1 72769-112 PELLET 96 mg ORAL NDA 31 sections
Orladeyo HUMAN PRESCRIPTION DRUG LABEL 1 72769-113 PELLET 108 mg ORAL NDA 31 sections
Orladeyo HUMAN PRESCRIPTION DRUG LABEL 1 72769-114 PELLET 132 mg ORAL NDA 31 sections