General
Preferred name
ANGIOTENSIN II
Synonyms
Angiotensin II human Acetate ()
Ang II acetate ()
DRVYIHPF acetate ()
Ang II ()
DRVYIHPF ()
Hypertensin II ()
ANGIOTENSIN II ACETATE ()
Angiotensin II human ()
Delivert ()
Giapreza ()
Angiotensin II human (acetate) ()
Human angiotensin II ()
Angiotensin II (acetate) ()
Ang II (acetate) ()
DRVYIHPF (acetate) ()
Asp-arg-val-tyr-ile-his-pro-phe ()
LJPC-501 ()
5-l-isoleucineangiotensin ii ()
Angiotensin ii (human type) ()
Angiotensin ii triacetate ()
Angiotensin ii acetate human ()
Human angiotensin ii acetate salt ()
Angiotensin II (human) (acetate) ()
P&D ID
PD014235
CAS
68521-88-0
4474-91-3
11128-99-7
Tags
natural product
drug
available
Approved by
EMA
FDA
First approval
2017
Drug indication
Increase blood pressure
Drug Status
approved
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
METABOLISM
It is metabolized by aminopeptidase A and angiotensin converting enzyme 2 to angiotensin-(2-8) [angiotensin III] and angiotensin-(1-7), respectively in plasma, erythrocytes and many of the major organs (i.e. intestine, kidney, liver and lung). Angiotensin II type 1 receptor (AT1) mediated activity of angiotensin III is approximately 40% of angiotensin II; however, aldosterone synthesis activity is similar to angiotensin II. Angiotensin-(1-7) exerts the opposite effects of angiotensin II on AT1 receptors and causes vasodilation [FDA Label].; ; Nevertheless, the official prescribing information also notes that no formal studies have been conducted that examine the metabolism of angiotensin II [FDA Label].
DESCRIPTION
Endogenous angiotensin II is a vasopressor.
(GtoPdb)
MOA
As part of the renin-angiotensin-aldosterone-system (RAAS), angiotensin II raises blood pressure by vasoconstriction, increased aldosterone release by the adrenal zona glomerulosa, sodium and water reabsorption in the proximal tubular cells, and vasopressin secretion [FDA Label, A31494]; ; The direct action of angiotensin II on surrounding vessel walls is facilitated by binding to the G-protein-coupled angiotensin II receptor type 1 (AT-1) on vascular smooth muscle cells, which stimulates Ca2+/calmodulin-dependent phosphorylation of myosin and causes smooth muscle contraction that results in vasoconstriction [FDA Label, A31494].; ; The RAAS is ultimately regulated by a negative feedback effect of angiotensin II on renin production by the juxtaglomerular cells of the renal afferent arteriole. Unresuscitated septic shock associated with marked hypovolemia, extracellular fluid volume depletion, decreased cardiac output, low arterial blood pressure and decreased systemic vascular resistance causes an increase in renin secretion by the juxtaglomerular cells, resulting in elevated angiotensin II plasma levels and an increased secretion of aldosterone from the adrenal cortex. Angiotensin II binding to AT-1 receptors causes dose-dependent vasoconstriction of both afferent and efferent glomerular arterioles. The most pronounced effect of angiotensin II results on efferent arterioles, resulting in reduced renal blood flow and increased glomerular filtration pressure. [A31494]
PHARMACODYNAMICS
Angiotensin II is a naturally occurring peptide hormone of the renin-angiotensin-aldosterone-system (RAAS) that has the capacity to cause vasoconstriction and an increase in blood pressure in the human body. [FDA Label]; ; In the RAAS, juxtaglomerular cells of the renal afferent arteriole synthesize the proteolytic enzyme renin. Although stored in an inactive form called pro-renin, decreases in arterial blood pressure or extracellular fluid volume depletion can cause various enzymatic reactions to release active renin into the systemic circulation and surrounding tissues. Such renin release allows for the production of the alpha-2-globulin angiotensinogen predominantly in the liver and to some extent, the kidneys and other organs. [A31494]; ; Angiotensin I, itself a decapeptide with weak biological activity, is produced from angiotensinogen and then quickly converted to angiotensin II by angiotensin converting enzymes (ACE). Consequently, angiotensin II demonstrates its strong vasopressor activity when it is rapidly degraded by aminopeptidases A and M into further entities like angiotensin III and angiotensin IV, respectively. Such species like angiotensin III can then bind and interact with specific G protein coupled receptors like angiotensin receptor 1, or AT-1 [A31494] where strong vasoconstricson can occur. [A31494]; ; Furthermore, in the ATHOS-3 clinical trial, for the 114 (70%) patient subjects in the angiotensin II arm who reached the target mean arterial pressure (MAP) at Hour 3, the median time to reach the target MAP endpoint was approximately 5 minutes. The angiotensin II was titrated to effect for each individual patient. [FDA Label].
TOXICITY
Overdose with angiotensin II would be expected to result in hypertension, necessitating close monitoring and supportive care [FDA Label]. Effects are also expected to be brief as the half-life of angiotensin II is less than one minute [FDA Label].; ; In the ATHOS-3 clinical study there was a higher incidence of arterial and venous thrombotic and thromboembolic events in patients who received angiotensin II compared to placebo treated patients. The major imbalance was in deep venous thromboses - which prompts the potential need to use concurrent venous thromboembolism (VTE) prohphylaxis [FDA Label].; ; Adverse effects of noticeable potential (>= 10%) include thromboembolic events (ie. like deep vein thrombosis) including arterial and venous thrombotic events, thrombocytopenia, tachycardia, and fungal infection. Effects whose potential are < 10% include delirium, acidosis, hyperglycemia, peripheral ischemia [FDA Label].; ; Concomitant use of angiotensin converting enzymes (ACE) inhibitors may increase the response of angiotensin II [FDA Label].; ; Concomitant use of angiotensin II blockers (ARBs) may decrease the response to angiotensin II [FDA Label].; ; There are no formal data regarding the safe use of angiotensin II in pregnant women. However, septic or other distributive shock is a medical emergency that can be fatal if left untreated. Delaying treatment in pregnant women with hypotension associated with septic or otherdistributive shock is likely to increase the risk of maternal and fetal morbidity and mortality [FDA Label].; ; There is no formal data regarding whether or not angiotensin II may become present in human milk and there is no data available on the effects of angiotensin II on the breastfed child or the effects on milk production [FDA Label].; ; The safety and efficacy of angiotensin II in pediatric patients has not yet been established [FDA Label].; ; There is no difference in the safety or efficacy between patients less than 65 years old and those 65 years or older when treated with angiotensin II [FDA Label].; ; There is no difference in pharmacokinetics between male and female patients [FDA Label].; ; The pharmacokinetics of angiotensin II are not expected to be influenced by renal impairment or hepatic impairment [FDA Label].
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
0
Organisms
1
Compound Sets
16
Cayman Chemical Bioactives
ChEMBL Approved Drugs
ChEMBL Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
Guide to Pharmacology
LSP-MoA library (Laboratory of Systems Pharmacology)
Natural product-based probes and drugs
NPC Screening Collection
Other bioactive compounds
ReFrame library
Selleckchem Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
60
Molecular Weight
1045.53
Hydrogen Bond Acceptors
13
Hydrogen Bond Donors
14
Rotatable Bonds
29
Ring Count
4
Aromatic Ring Count
3
cLogP
-1.11
TPSA
406.34
Fraction CSP3
0.5
Chiral centers
9.0
Largest ring
6.0
QED
0.02
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Pathway
Endocrinology/Hormones
Apoptosis
GPCR/G protein
Target
angiotensin AT1?receptor
AT receptor
Angiotensin Receptor
Biosynthetic Origin
Peptide (Ribosomal)
Therapeutic Indication
Anticancer
Antihypertensive
Therapeutic Class
Cardiovascular
Source data
