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angiotensin II 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |
| Stem definition | Drug id | CAS RN |
|---|---|---|
| 5272 | 4474-91-3 |
Description:
| Molecule | Description |
|---|---|
|
Synonyms:
|
Angiotensin II is a naturally occurring peptide hormone of the renin-angiotensin-aldosterone system (RAAS) that causes vasoconstriction and an increase in blood pressure. Angiotensin II raises blood pressure by vasoconstriction and increased aldosterone release. Direct action of angiotensin II on the vessel wall is mediated by binding to the G-protein-coupled angiotensin II receptor type 1 on vascular smooth muscle cells, which stimulates Ca2+/calmodulin-dependent phosphorylation of myosin and causes smooth muscle contraction.
Legend: OFP - off patent OFM - off market ONP - on patent |
Drug dosage:
None
ADMET properties:
None
Predicted pharmacokinetic/toxicological properties (PK-AZ):
| Property | Description | Value | Unit | Confidence | Similarity |
|---|---|---|---|---|---|
| azlogd74 | LogD at pH 7.4 | -0.886 | High | 0.86 | |
| caco2-efflux | Caco-2 efflux ratio (BA/AB) | 1.510 | High | 0.86 | |
| caco2-intrinsic-papp | Caco-2 intrinsic apparent permeability | 0.274 | 10^-6 cm/s | High | 0.86 |
| dh-clint | Dog hepatocyte intrinsic clearance | 1.396 | uL/min/10^6 cells | High | 0.86 |
| dppb | Dog plasma protein binding (% unbound) | 70 | % | High | 0.86 |
| fcs-ppb | Fetal calf serum protein binding (% unbound) | 36.580 | % | High | 0.86 |
| herg | hERG pIC50 | 4.663 | pIC50 | High | 0.86 |
| hh-clint | Human hepatocyte intrinsic clearance | 40.272 | uL/min/10^6 cells | High | 0.86 |
| hlm-clint | Human liver microsomal intrinsic clearance | 6.412 | uL/min/mg protein | High | 0.86 |
| hppb | Human plasma protein binding (% unbound) | 63.580 | % | High | 0.86 |
| kinase-safety-class | ACVR2B,AXL,BRAF,BTK,CAMK2D,CDK5,CDK9,EIF2AK3,ERBB2,GRK2,ITK,MAP2K6,MAPK7,NTRK2,PDK1,PDK2,PDK4,PIK3CB,PRKDC,TEK,TGFBR1 | 21 | |||
| kinase-selectivity-class | GRK2,PDK1 | 2 | |||
| mdck-mdr1-efflux | MDCK-MDR1 efflux ratio | 2.249 | High | 0.86 | |
| mh-clint | Mouse hepatocyte intrinsic clearance | 56.624 | High | 0.86 | |
| mppb | Mouse plasma protein binding (% unbound) | 48.730 | High | 0.86 | |
| nih-mdck-mdr1-efflux | NIH MDCK-MDR1 efflux ratio | 1.361 | High | 0.86 | |
| pfas-class | PFAS structural alert (1 = True, 0 = False) | 0 | |||
| pppb | Pig plasma protein binding (% unbound) | 41.950 | % | High | 0.86 |
| rh-clint | Rat hepatocyte intrinsic clearance | 54.075 | uL/min/10^6 cells | High | 0.86 |
| rh-fuinc | Rat hepatocyte fraction unbound in incubation | 43.930 | % | High | 0.86 |
| rppb | Rat plasma protein binding (% unbound) | 44.720 | % | High | 0.86 |
| solubility-dd | Solubility at pH 7.4 in DMSO | 428.549 | uM | High | 0.86 |
Approvals:
| Date | Agency | Company | Orphan |
|---|---|---|---|
| Aug. 23, 2019 | EMA | La Jolla Pharmaceutical II B.V. | |
| Dec. 21, 2017 | FDA | LA JOLLA PHARMACEUTICAL CO |
FDA Adverse Event Reporting System (Female)
None
FDA Adverse Event Reporting System (Male)
| 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 |
|---|---|---|---|---|---|---|
| Drug ineffective | 88.95 | 71.73 | 49 | 186 | 630148 | 41990952 |
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 |
|---|---|---|---|---|---|---|
| Drug ineffective | 99.83 | 76.91 | 62 | 326 | 1520478 | 109068433 |
FDA Adverse Event Reporting System (Pediatric)
None
Pharmacologic Action:
| Source | Code | Description |
|---|---|---|
| ATC | C01CX09 | CARDIOVASCULAR SYSTEM CARDIAC THERAPY CARDIAC STIMULANTS EXCL. CARDIAC GLYCOSIDES Other cardiac stimulants |
| MeSH PA | D002317 | Cardiovascular Agents |
| MeSH PA | D014662 | Vasoconstrictor Agents |
| FDA PE | N0000009908 | Vasoconstriction |
| FDA EPC | N0000192562 | Vasoconstrictor |
| CHEBI has role | CHEBI:50514 | vasoconstrictor agent |
Related Drugs by ATC class:
C01CX Other cardiac stimulants 3 drugs
Drug Use | Suggest Off label Use Form| |View source of the data|
| Disease | Relation | SNOMED_ID | DOID |
|---|---|---|---|
| Septic shock | symptomatic treatment | 76571007 |
🐶 Veterinary Drug Use
None
🐶 Veterinary products
None
Acid dissociation constants calculated using MoKa v3.0.0
| Dissociation level | Dissociation constant | Type (acidic/basic) |
|---|---|---|
| pKa1 | 2.68 | acidic |
| pKa2 | 3.61 | acidic |
| pKa3 | 9.65 | acidic |
| pKa4 | 13.04 | acidic |
| pKa5 | 13.86 | acidic |
| pKa6 | 10.75 | Basic |
| pKa7 | 8.45 | Basic |
| pKa8 | 6.3 | Basic |
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 0.5MG BASE/ML (EQ 0.5MG BASE/ML) | GIAPREZA | LA JOLLA PHARMA | N209360 | Dec. 23, 2021 | RX | SOLUTION | INTRAVENOUS | 10335451 | Dec. 16, 2029 | TREATING HYPOTENSION WITH ABOUT 20 NG/KG/MIN TO ABOUT 40 NG/KG/MIN ANGIOTENSIN II IN A HUMAN SUBJECT HAVING SEPTIC SHOCK |
| EQ 0.5MG BASE/ML (EQ 0.5MG BASE/ML) | GIAPREZA | LA JOLLA PHARMA | N209360 | Dec. 23, 2021 | RX | SOLUTION | INTRAVENOUS | 10500247 | Dec. 16, 2029 | TREATING LOW BLOOD PRESSURE WITH ANGIOTENSIN II WITH AN INITIAL RATE OF ABOUT 5 NG/KG/MIN TO ABOUT 20 NG/KG/MIN IN A SUBJECT HAVING REFRACTORY HYPOTENSION OR SEVERE HYPOTENSION |
| EQ 0.5MG BASE/ML (EQ 0.5MG BASE/ML) | GIAPREZA | LA JOLLA PHARMA | N209360 | Dec. 23, 2021 | RX | SOLUTION | INTRAVENOUS | 10500247 | Dec. 16, 2029 | TREATING LOW BLOOD PRESSURE WITH ANGIOTENSIN II WITH AN INITIAL RATE OF ABOUT 5 NG/KG/MIN TO ABOUT 20 NG/KG/MIN IN A SUBJECT HAVING REFRACTORY HYPOTENSION OR SEVERE HYPOTENSION, AND TITRATING THE RATE UP |
| EQ 0.5MG BASE/ML (EQ 0.5MG BASE/ML) | GIAPREZA | LA JOLLA PHARMA | N209360 | Dec. 23, 2021 | RX | SOLUTION | INTRAVENOUS | 10548943 | Dec. 16, 2029 | INCREASING BLOOD PRESSURE WITH AN INITIAL RATE OF ABOUT 20 NG/KG/MIN ANGIOTENSIN II IN A HUMAN SUBJECT HAVING SEPTIC SHOCK, AND TITRATING THE RATE UP. |
| EQ 0.5MG BASE/ML (EQ 0.5MG BASE/ML) | GIAPREZA | LA JOLLA PHARMA | N209360 | Dec. 23, 2021 | RX | SOLUTION | INTRAVENOUS | 10548943 | Dec. 16, 2029 | INCREASING BLOOD PRESSURE WITH A RATE OF ABOUT 20 NG/KG/MIN TO ABOUT 40 NG/KG/MIN ANGIOTENSIN II IN A HUMAN SUBJECT HAVING SEPTIC SHOCK |
| EQ 0.5MG BASE/ML (EQ 0.5MG BASE/ML) | GIAPREZA | LA JOLLA PHARMA | N209360 | Dec. 23, 2021 | RX | SOLUTION | INTRAVENOUS | 9867863 | Dec. 16, 2029 | TREATING REFRACTORY HYPOTENSION WITH ABOUT 5 NG/KG/MIN TO ABOUT 20 NG/KG/MIN ANGIOTENSIN II IN A PATIENT RECEIVING VASOPRESSOR |
| EQ 0.5MG BASE/ML (EQ 0.5MG BASE/ML) | GIAPREZA | LA JOLLA PHARMA | N209360 | Dec. 23, 2021 | RX | SOLUTION | INTRAVENOUS | 9572856 | July 18, 2031 | TREATING REFRACTORY HYPOTENSION WITH ABOUT 20 NG/KG/MIN ANGIOTENSIN II IN A PATIENT RECEIVING VASOPRESSOR |
| EQ 0.5MG BASE/ML (EQ 0.5MG BASE/ML) | GIAPREZA | LA JOLLA PHARMA | N209360 | Dec. 23, 2021 | RX | SOLUTION | INTRAVENOUS | 10028995 | Dec. 18, 2034 | MAINTAINING MEAN ARTERIAL PRESSURE OF ABOUT 65 MMHG OR ABOVE WITH ABOUT 1 NG/KG/MIN TO ABOUT 40 NG/KG/MIN ANGIOTENSIN II IN HYPOTENSIVE PATIENTS TREATED WITH VASOPRESSIN OR A VASOPRESSIN ANALOGUE AND REDUCING VASOPRESSIN OR VASOPRESSIN ANALOGUE USE |
| EQ 0.5MG BASE/ML (EQ 0.5MG BASE/ML) | GIAPREZA | LA JOLLA PHARMA | N209360 | Dec. 23, 2021 | RX | SOLUTION | INTRAVENOUS | 10493124 | Dec. 18, 2034 | TREATING LOW BLOOD PRESSURE WITH ANGIOTENSIN II AT AN INITIAL RATE OF ABOUT 20 NG/KG/MIN AND TITRATING DOWN TO ACHIEVE AND/OR MAINTAIN A MAP OF ABOUT 65 MM HG OR ABOVE |
| EQ 0.5MG BASE/ML (EQ 0.5MG BASE/ML) | GIAPREZA | LA JOLLA PHARMA | N209360 | Dec. 23, 2021 | RX | SOLUTION | INTRAVENOUS | 11096983 | Dec. 18, 2034 | TREATING DISTRIBUTIVE SHOCK WITH ANGIOTENSIN II |
| EQ 0.5MG BASE/ML (EQ 0.5MG BASE/ML) | GIAPREZA | LA JOLLA PHARMA | N209360 | Dec. 23, 2021 | RX | SOLUTION | INTRAVENOUS | 11096983 | Dec. 18, 2034 | TREATING SEPTIC SHOCK WITH ANGIOTENSIN II |
| EQ 0.5MG BASE/ML (EQ 0.5MG BASE/ML) | GIAPREZA | LA JOLLA PHARMA | N209360 | Dec. 23, 2021 | RX | SOLUTION | INTRAVENOUS | 11559559 | Dec. 18, 2034 | INCREASING BLOOD PRESSURE IN A PATIENT HAVING DISTRIBUTIVE SHOCK |
| EQ 0.5MG BASE/ML (EQ 0.5MG BASE/ML) | GIAPREZA | LA JOLLA PHARMA | N209360 | Dec. 23, 2021 | RX | SOLUTION | INTRAVENOUS | 9220745 | Dec. 18, 2034 | MAINTAINING MEAN ARTERIAL PRESSURE OF ABOUT 65 MMHG OR HIGHER WITH ANGIOTENSIN II IN SHOCK PATIENTS TREATED WITH CATECHOLAMINES AND REDUCING CATECHOLAMINE USE |
| EQ 0.5MG BASE/ML (EQ 0.5MG BASE/ML) | GIAPREZA | LA JOLLA PHARMA | N209360 | Dec. 23, 2021 | RX | SOLUTION | INTRAVENOUS | 9220745 | Dec. 18, 2034 | TREATING HIGH OUTPUT SHOCK WITH ANGIOTENSIN II BY INCREASING MEAN ARTERIAL PRESSURE IN PATIENTS TREATED WITH CATECHOLAMINES AND REDUCING CATECHOLAMINE USE |
| EQ 0.5MG BASE/ML (EQ 0.5MG BASE/ML) | GIAPREZA | LA JOLLA PHARMA | N209360 | Dec. 23, 2021 | RX | SOLUTION | INTRAVENOUS | 11219662 | Jan. 6, 2037 | TREATING HYPOTENSION WITH ANGIOTENSIN II IN A PATIENT RECEIVING AN ANGIOTENSIN CONVERTING ENZYME INHIBITOR |
Orange Book exclusivity data (new drug applications)
None
Bioactivity Summary:
| Target | Class | Pharos | UniProt | Action | Type | Activity value (-log[M]) | Mechanism action | Bioact source | MoA source |
|---|---|---|---|---|---|---|---|---|---|
| Type-1 angiotensin II receptor | GPCR | AGONIST | IC50 | 9.30 | IUPHAR | DRUG LABEL | |||
| Type-2 angiotensin II receptor | GPCR | AGONIST | Kd | 10.20 | IUPHAR | ||||
| Type-1B angiotensin II receptor | GPCR | Ki | 9.51 | CHEMBL | |||||
| Type-1 angiotensin II receptor | GPCR | Kd | 8.24 | CHEMBL | |||||
| Type-1A angiotensin II receptor | GPCR | IC50 | 9.40 | CHEMBL |
External reference:
| ID | Source |
|---|---|
| M089EFU921 | UNII |
| 4037288 | VANDF |
| C0373546 | UMLSCUI |
| CHEBI:2719 | CHEBI |
| CHEMBL408403 | ChEMBL_ID |
| CHEMBL2392353 | ChEMBL_ID |
| 172198 | PUBCHEM_CID |
| DB11842 | DRUGBANK_ID |
| CHEMBL3989932 | ChEMBL_ID |
| D00150 | KEGG_DRUG |
| D000804 | MESH_DESCRIPTOR_UI |
| 6707 | INN_ID |
| 2504 | IUPHAR_LIGAND_ID |
| C000627694 | MESH_SUPPLEMENTAL_RECORD_UI |
| 764385008 | SNOMEDCT_US |
| 85267009 | SNOMEDCT_US |
| 267286 | MMSL |
| d08691 | MMSL |
| 1999003 | RXNORM |
| M089EFU921 | INXIGHT DRUGS |
Pharmaceutical products:
| Product | Category | Ingredients | NDC | Form | Quantity | Route | Marketing | Label |
|---|---|---|---|---|---|---|---|---|
| ANGIOTENSIN II | Human Prescription Drug Label | 1 | 68083-553 | INJECTION | 2.50 mg | INTRAVENOUS | ANDA | 26 sections |
| Giapreza | HUMAN PRESCRIPTION DRUG LABEL | 1 | 68547-005 | INJECTION | 0.50 mg | INTRAVENOUS | NDA | 27 sections |
| Giapreza | HUMAN PRESCRIPTION DRUG LABEL | 1 | 68547-501 | INJECTION | 2.50 mg | INTRAVENOUS | NDA | 27 sections |