enalaprilat ๐Ÿถ Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
angiotensin-converting enzyme inhibitors 1006 76420-72-9

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • enalaprilat
  • enalapril acid
  • enalaprilate
  • enalaprilic acid
  • enalaprilat hydrate
  • enalaprilat dihydrate
The active metabolite of ENALAPRIL and one of the potent, intravenously administered, ANGIOTENSIN-CONVERTING ENZYME INHIBITORS. It is an effective agent for the treatment of essential hypertension and has beneficial hemodynamic effects in heart failure. The drug produces renal vasodilation with an increase in sodium excretion.
  • Molecular weight: 348.40
  • Formula: C18H24N2O5
  • CLOGP: 0.75
  • LIPINSKI: 0
  • HAC: 7
  • HDO: 3
  • TPSA: 106.94
  • ALOGS: -2.60
  • ROTB: 8

  • Status: OFP

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

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 60 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 1.91 ยตM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 40 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.38 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 1.60 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.62 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 39 hours Lombardo F, Berellini G, Obach RS
S (Water solubility) 14 mg/mL Bocci G, Oprea TI, Benet LZ

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 -2.165 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 0.446 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 0.233 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 2.123 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 89.490 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 78.410 % High 1
herg hERG pIC50 4.409 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 1.496 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 3.258 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 89.380 % High 1
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 0.337 High 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 0.333 High 1
mh-clint Mouse hepatocyte intrinsic clearance 2.564 High 1
mppb Mouse plasma protein binding (% unbound) 96.870 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 0.249 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 91.340 % High 1
rat-kpuu-brain Rat brain Kpuu 0.003 % High 1
rh-clint Rat hepatocyte intrinsic clearance 0.818 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 91.850 % High 1
rppb Rat plasma protein binding (% unbound) 88.860 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 907.821 uM High 1

Approvals:

DateAgencyCompanyOrphan
Feb. 9, 1988 FDA BIOVAIL LABS INTL

FDA Adverse Event Reporting System (Female)

None

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
Angioedema 50.89 43.28 13 90 42464 42578768

FDA Adverse Event Reporting System (Geriatric)

None

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
MeSH PA D000806 Angiotensin-Converting Enzyme Inhibitors
MeSH PA D000959 Antihypertensive Agents
MeSH PA D002317 Cardiovascular Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D011480 Protease Inhibitors
CHEBI has role CHEBI:35457 EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor
CHEBI has role CHEBI:35554 cardiovascular drug
CHEBI has role CHEBI:35674 antihypertensive agent

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

DiseaseRelationSNOMED_IDDOID
Hypertensive disorder indication 38341003 DOID:10763
Congestive heart failure indication 42343007 DOID:6000
Asymptomatic left ventricular systolic dysfunction indication 698592004
Angioedema contraindication 41291007 DOID:1558
Hereditary angioneurotic edema contraindication 82966003 DOID:14735
Idiopathic angioedema contraindication 402382008




๐Ÿถ Veterinary Drug Use

None

๐Ÿถ Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 2.12 acidic
pKa2 3.14 acidic
pKa3 8.3 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Angiotensin-converting enzyme Enzyme INHIBITOR IC50 7.50 IUPHAR IUPHAR
Angiotensin-converting enzyme Enzyme Ki 8.85 CHEMBL
Angiotensin-converting enzyme Enzyme IC50 9.02 CHEMBL
Angiotensin-converting enzyme 2 Enzyme Ki 9.30 CHEMBL
Angiotensin-converting enzyme Enzyme IC50 7.94 CHEMBL

External reference:

IDSource
4019497 VUID
N0000147617 NUI
D03769 KEGG_DRUG
4019497 VANDF
C0014027 UMLSCUI
CHEBI:4786 CHEBI
CHEMBL3989406 ChEMBL_ID
DB09477 DRUGBANK_ID
D015773 MESH_DESCRIPTOR_UI
5462501 PUBCHEM_CID
6332 IUPHAR_LIGAND_ID
84680-54-6 SECONDARY_CAS_RN
2672730 RXNORM
37933 MMSL
4657 MMSL
004369 NDDF
007388 NDDF
1013031000202101 SNOMEDCT_US
414092003 SNOMEDCT_US
48052001 SNOMEDCT_US
EAL PDB_CHEM_ID
GV0O7ES0R3 UNII
GV0O7ES0R3 INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Enalaprilat HUMAN PRESCRIPTION DRUG LABEL 1 0143-9786 INJECTION 2.50 mg INTRAVENOUS ANDA 23 sections
Enalaprilat HUMAN PRESCRIPTION DRUG LABEL 1 0143-9787 INJECTION 1.25 mg INTRAVENOUS ANDA 23 sections
Enalaprilat HUMAN PRESCRIPTION DRUG LABEL 1 43598-078 INJECTION 1.25 mg INTRAVENOUS ANDA 23 sections
Enalaprilat HUMAN PRESCRIPTION DRUG LABEL 1 43598-169 INJECTION 2.50 mg INTRAVENOUS ANDA 23 sections
ENALAPRILAT HUMAN PRESCRIPTION DRUG LABEL 1 51662-1477 INJECTION 1.25 mg INTRAVENOUS ANDA 13 sections