Angiotensin II
Accession Number
Small Molecule
Approved, Investigational

Angiotensin II is under investigation for the treatment of Sepsis, Septic Shock, Diabetes Mellitus, and Acute Renal Failure. Angiotensin II has been investigated for the treatment, basic science, and diagnostic of Hypertension, Renin Angiotensin System, and Idiopathic Membranous Nephropathy.

As of December 21, 2017 the FDA approved La Jolla Pharmaceutical's Giapreza (angiotensin II) Injection for Intravenouse Infusion for the indication of acting as a vasoconstrictor to increase blood pressure in adults with septic or other distributive shock. The novelty of the medication lies in the fact that it is the first and only use of synthetic human angiotensin II to help maintain body blood pressure.

Shock is the inability to maintain blood flow to vital tissues and the potential resultant organ failure and death within hours, no matter young or o ld. As distributive shock is the most common type of shock in the inpatient setting and affects up to one third of patients in the intensive care unit, the FDA determined that there is a need for treatment options for critically ill hypotensive patients who do not adequately respond to currently available therapies.

  • 5-isoleucine-angiotensin II
  • 5-L-isoleucineangiotensin II
  • Angiotensin
  • Angiotensin II
  • Angiotensin II (human)
  • Angiotonin
  • Human angiotensin II
  • Hypertensin
  • Ile5-angiotensin II
  • isoleucine5-angiotensin II
Product Ingredients
IngredientUNIICASInChI Key
Angiotensin II acetate31L3HS630A32044-01-2VBTZKFAHKJXHBA-PIONDTTLSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
GiaprezaInjection2.5 mg/1mLIntravenousLa Jolla Pharmaceutical Company2018-02-05Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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CAS number
Average: 1046.1786
Monoisotopic: 1045.534514801
Chemical Formula
InChI Key
(3S)-3-amino-3-{[(1S)-1-{[(1S)-1-{[(1S)-1-{[(1S,2S)-1-{[(2S)-1-[(2S)-2-{[(1S)-1-carboxy-2-phenylethyl]carbamoyl}pyrrolidin-1-yl]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]carbamoyl}-2-methylbutyl]carbamoyl}-2-(4-hydroxyphenyl)ethyl]carbamoyl}-2-methylpropyl]carbamoyl}-4-[(diaminomethylidene)amino]butyl]carbamoyl}propanoic acid



Angiotensin II is a vasoconstrictor indicated for increasing blood pressure in adults with septic or other distributive shock Label.

Associated Conditions

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. 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. 1

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 1 where strong vasoconstricson can occur. 1

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. Label.

Mechanism of action

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 Label,1

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 Label,1.

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. 1

AType-1 angiotensin II receptor
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Blackbox Warnings

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Following the intravenous infusion of angiotensin II in adult patients with septic or other distributive shock, the serum levels of angiotensin II observed were similar at baseline and hour 3 after the intravenous infusion. After 3 hours of treatment, the serum level of angiotensin I (the angiotensin II precursos peptide) is however, reduced by about 40% Label.

Volume of distribution

The official prescribing information for angiotensin II notes that no specific studies have yet been conducted that examine the distribution of angiotensin II Label.

Protein binding
Not Available

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 Label.

Nevertheless, the official prescribing information also notes that no formal studies have been conducted that examine the metabolism of angiotensin II Label.

Route of elimination

The official prescribing information notes that no specific studies have been conducted that examine the elimination of angiotensin II.

Half life

The plasma half-life of intravenously administered angiotensin II is less than one minute Label.


The official prescribing information notes that the clearnace of angiotensin II is not dependent on hepatic function or renal function Label.


Overdose with angiotensin II would be expected to result in hypertension, necessitating close monitoring and supportive care Label. Effects are also expected to be brief as the half-life of angiotensin II is less than one minute 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 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 Label.

Concomitant use of angiotensin converting enzymes (ACE) inhibitors may increase the response of angiotensin II Label.

Concomitant use of angiotensin II blockers (ARBs) may decrease the response to angiotensin II 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 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 Label.

The safety and efficacy of angiotensin II in pediatric patients has not yet been established 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 Label.

There is no difference in pharmacokinetics between male and female patients Label.

The pharmacokinetics of angiotensin II are not expected to be influenced by renal impairment or hepatic impairment Label.

Affected organisms
  • Humans and other mammals
Not Available
Pharmacogenomic Effects/ADRs
Not Available


Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
LevothyroxineLevothyroxine may increase the vasoconstricting activities of Angiotensin II.
LidocaineThe risk or severity of hypertension can be increased when Angiotensin II is combined with Lidocaine.
LiothyronineLiothyronine may increase the vasoconstricting activities of Angiotensin II.
LiotrixLiotrix may increase the vasoconstricting activities of Angiotensin II.
Patent BlueThe risk or severity of hypotension can be increased when Patent Blue is combined with Angiotensin II.
Thyroid, porcineThyroid, porcine may increase the vasoconstricting activities of Angiotensin II.
Thyrotropin alfaThyrotropin alfa may increase the vasoconstricting activities of Angiotensin II.
TiratricolTiratricol may increase the vasoconstricting activities of Angiotensin II.
Additional Data Available
  • Extended Description
    Extended Description

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  • Action

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Food Interactions
No interactions found.


General References
  1. Correa TD, Takala J, Jakob SM: Angiotensin II in septic shock. Crit Care. 2015 Mar 16;19:98. doi: 10.1186/s13054-015-0802-3. [PubMed:25886853]
External Links
Human Metabolome Database
KEGG Compound
PubChem Compound
PubChem Substance
ATC Codes
C01CX09 — Angiotensin ii
FDA label
Download (2.45 MB)

Clinical Trials

Clinical Trials
0RecruitingBasic ScienceBMI >30 kg/m2 / High Blood Pressure (Hypertension)1
0RecruitingOtherBMI >30 kg/m21
0RecruitingTreatmentDisorders of the Autonomic Nervous System / Orthostatic Hypotension, Dysautonomic / Progressive autonomic failure / Shy-Drager Syndrome1
0RecruitingTreatmentPeripheral Arterial Disease (PAD)1
1Active Not RecruitingOtherHigh Blood Pressure (Hypertension) / Insulin Resistance1
1Active Not RecruitingTreatmentHigh Blood Pressure (Hypertension)1
1CompletedNot AvailableRAS Peptide Profile in Healthy Volunteers1
1CompletedBasic SciencePostural Orthostatic Tachycardia Syndrome (POTS) / Postural Tachycardia Syndrome1
1CompletedTreatmentShock, Septic1
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1RecruitingBasic ScienceChronic Obstructive Pulmonary Disease (COPD) / Heart Failure / High Blood Pressure (Hypertension) / Pulmonary Arterial Hypertension (PAH)1
1RecruitingOtherBMI >30 kg/m2 / High Blood Pressure (Hypertension) / Insulin Resistance / Metabolic Cardiovascular Syndrome1
1RecruitingOtherHigh Blood Pressure (Hypertension) / Hypertension,Essential1
1, 2Unknown StatusTreatmentRenal Insufficiency,Chronic1
2Active Not RecruitingTreatmentConnective Tissue Disorders / Oesophagitis, Eosinophilic1
2CompletedPreventionRheumatoid Arthritis1
2CompletedTreatmentBone Cancer / Chondrosarcomas / Clear Cell Sarcoma of the Kidney / Metastatic Bone Sarcomas / Ovarian Sarcoma / Recurrent Adult Soft Tissue Sarcoma / Recurrent Osteosarcoma / Recurrent Uterine Sarcoma / Stage III Adult Soft Tissue Sarcoma / Stage III Uterine Sarcoma / Stage IV Adult Soft Tissue Sarcoma / Stage IV Uterine Sarcoma1
2CompletedTreatmentCatecholamine-resistant Hypotension (CRH) / Distributive shock / High Output Shock / Sepsis1
2CompletedTreatmentChronic Heart Failure (CHF) / Cognitive Impairments1
2CompletedTreatmentCluster Headache1
2CompletedTreatmentDiabetic Foot / Diabetic Foot Ulcers (DFU)1
2CompletedTreatmentHypertrophic Cardiomyopathy (HCM)1
2RecruitingTreatmentCatecholamine-resistant Hypotension (CRH) / Distributive shock / High Output Shock / Shock, Septic1
2RecruitingTreatmentHenoch-Schoenlein Purpura Nephritis1
2TerminatedTreatmentCardiovascular Heart Disease / High Blood Pressure (Hypertension)1
2TerminatedTreatmentCognitive Impairments / Coronary Artery Bypass Graft Surgery Patients1
2Unknown StatusTreatmentAcute Renal Failure (ARF) / Sepsis / Shock, Septic1
2WithdrawnBasic ScienceHeart Failure1
2, 3Active Not RecruitingPreventionCognitively Normal Older Adults / Family History of Alzheimer's Disease / High Blood Pressure (Hypertension) / Subjective Cognitive Decline1
2, 3CompletedPreventionAtrial Fibrillation (AF)1
2, 3CompletedPreventionSystemic Lupus Erythematosus (SLE)1
3Active Not RecruitingTreatmentIdiopathic Membranous Nephropathy1
3CompletedPreventionAtrial Fibrillation (AF)1
3CompletedPreventionCardiovascular Heart Disease / Coronary Heart Disease (CHD) / Heart Diseases / Myocardial Infarction / Myocardial Ischemia1
3CompletedTreatmentAcquired Kidney Disease / Children / Chronic Renal Failure (CRF) / Congenital Kidney Disease / High Blood Pressure (Hypertension)1
3CompletedTreatmentAtherosclerosis / Congestive Heart Failure / High Blood Pressure (Hypertension) / Myocardial Infarction2
3CompletedTreatmentCardiovascular Heart Disease / Congestive Heart Failure / Heart Diseases / Heart Failure / Myocardial Infarction1
3CompletedTreatmentCardiovascular Heart Disease / Coronary Heart Disease (CHD) / Diabetes Mellitus / Diabetes Mellitus, Non-Insulin-Dependent / Heart Diseases / Insulin Resistance / Type 2 Diabetes Mellitus1
3CompletedTreatmentCatecholamine-resistant Hypotension (CRH) / Distributive shock / High Output Shock / Sepsis1
3CompletedTreatmentHeart Failure1
3CompletedTreatmentHigh Blood Pressure (Hypertension)1
3RecruitingPreventionCardiovascular Heart Disease / Myocardial Infarction1
3RecruitingTreatmentIgA Nephropathy1
3RecruitingTreatmentRheumatoid Arthritis1
3SuspendedTreatmentShock, Septic1
3TerminatedTreatmentIgA Nephropathy1
4Active Not RecruitingTreatmentBody Composition / Exercise Tolerance / Heart Failure / Strength, Muscle / Vasodilation1
4Active Not RecruitingTreatmentDiabetes / Hypertensive Disease1
4CompletedDiagnosticHigh Blood Pressure (Hypertension)1
4CompletedOtherDyslipidemia / High Blood Pressure (Hypertension)1
4CompletedPreventionCardiovascular Heart Disease1
4CompletedPreventionHigh Blood Pressure (Hypertension) / Infarction, Brain1
4CompletedPreventionKidney Stones1
4CompletedTreatmentDiabetic Nephropathies / Persistent Proteinuria With Type II Diabetes1
4CompletedTreatmentHigh Blood Pressure (Hypertension)1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
4CompletedTreatmentIgA Glomerulonephritis1
4CompletedTreatmentIgA Nephropathy2
4CompletedTreatmentSmall Abdominal Aortic Aneurysm1
4Not Yet RecruitingTreatmentAcute Renal Failure (ARF) / Hepatorenal Syndrome / Liver Cirrhosis1
4Not Yet RecruitingTreatmentMyocardial Infarction With Non-obstructive Coronary Arteries1
4RecruitingPreventionHigh Blood Pressure (Hypertension) / Novel Coronavirus Infectious Disease (COVID-19)1
4RecruitingPreventionHigh Blood Pressure (Hypertension) / Stroke / Transient Ischaemic Attack (TIA)1
4RecruitingTreatmentCardiovascular Heart Disease / Diabetes Mellitus1
4RecruitingTreatmentChronic Renal Failure (CRF)1
4RecruitingTreatmentHigh Blood Pressure (Hypertension)2
4RecruitingTreatmentNovel Coronavirus Infectious Disease (COVID-19)2
4RecruitingTreatmentProteinuria / Renal Insufficiency,Chronic1
4SuspendedTreatmentDiabetic Nephropathy Type 2 / Renal Insufficiency,Chronic1
4TerminatedPreventionNeurological Dysphagia / Pneumonia1
4TerminatedTreatmentCongestive Heart Failure1
4Unknown StatusTreatmentHigh Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
Not AvailableActive Not RecruitingNot AvailableDiabetes Mellitus1
Not AvailableActive Not RecruitingNot AvailableHenoch-Schoenlein Purpura Nephritis1
Not AvailableActive Not RecruitingNot AvailableHigh Blood Pressure (Hypertension)1
Not AvailableActive Not RecruitingNot AvailableHigh Blood Pressure (Hypertension) / Melanoma / Non-Melanoma Skin Cancer (NMSC)1
Not AvailableActive Not RecruitingNot AvailablePeritoneal dialysis therapy1
Not AvailableCompletedNot AvailableAging / High Blood Pressure (Hypertension)1
Not AvailableCompletedNot AvailableFabry's Disease / Proteinuria1
Not AvailableCompletedNot AvailableHigh Blood Pressure (Hypertension)1
Not AvailableCompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedNot AvailableHypertension Resistant To Conventional Therapy / Myocardial Infarction / Stroke / Systemic Arterial Hypertension1
Not AvailableCompletedBasic ScienceHeart Diseases / Vasodilation1
Not AvailableCompletedBasic ScienceInsulin Sensitivity / Microcirculation1
Not AvailableCompletedBasic ScienceRenin Angiotensin System1
Not AvailableCompletedPreventionCardiovascular Heart Disease / Coronary Heart Disease (CHD) / Heart Diseases1
Not AvailableCompletedPreventionHypoglycemia / Type 1 Diabetes Mellitus1
Not AvailableCompletedPreventionImpaired Glucose Tolerance / Prediabetic State1
Not AvailableCompletedTreatmentCardiovascular Heart Disease / Chronic Kidney Disease (CKD)1
Not AvailableCompletedTreatmentCongenital Heart Disease (CHD)1
Not AvailableCompletedTreatmentDiabetic Nephropathies / Proteinuria1
Not AvailableCompletedTreatmentHigh Blood Pressure (Hypertension) / OSAS (Obstructive Sleep Apneas Syndrome)1
Not AvailableCompletedTreatmentHypertension,Essential1
Not AvailableCompletedTreatmentRenal Function Disorder1
Not AvailableRecruitingNot AvailableAcute Respiratory Distress Syndrome (ARDS) / COVID / Novel Coronavirus Infectious Disease (COVID-19)1
Not AvailableRecruitingNot AvailableAdrenal Gland Diseases / Aldosterone Disorder / Blood Pressures1
Not AvailableRecruitingNot AvailableHigh Blood Pressure (Hypertension) / Novel Coronavirus Infectious Disease (COVID-19)1
Not AvailableRecruitingNot AvailableIgA Nephropathy / Immunosuppressive Treatment / Proteinuria in Nephrotic Range1
Not AvailableRecruitingNot AvailableNovel Coronavirus Infectious Disease (COVID-19)1
Not AvailableRecruitingPreventionAtherosclerosis / Nephritis, Lupus1
Not AvailableRecruitingTreatmentNovel Coronavirus Infectious Disease (COVID-19)1
Not AvailableTerminatedNot AvailableHigh Blood Pressure (Hypertension)1
Not AvailableTerminatedTreatmentHeart Failure2
Not AvailableUnknown StatusPreventionDiabetes Mellitus / Endocrine System Diseases / Glucose Metabolism Disorders / Metabolic Diseases1
Not AvailableWithdrawnOtherHigh Blood Pressure (Hypertension)1


Not Available
Not Available
Dosage forms
InjectionIntravenous2.5 mg/1mL
Not Available
Patent NumberPediatric ExtensionApprovedExpires (estimated)
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Experimental Properties
Not Available
Predicted Properties
Water Solubility0.0156 mg/mLALOGPS
pKa (Strongest Acidic)3.15ChemAxon
pKa (Strongest Basic)10.83ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count17ChemAxon
Hydrogen Donor Count13ChemAxon
Polar Surface Area408.84 Å2ChemAxon
Rotatable Bond Count29ChemAxon
Refractivity269.81 m3·mol-1ChemAxon
Polarizability107.02 Å3ChemAxon
Number of Rings4ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available


Mass Spec (NIST)
Not Available
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available


This compound belongs to the class of organic compounds known as oligopeptides. These are organic compounds containing a sequence of between three and ten alpha-amino acids joined by peptide bonds.
Organic compounds
Super Class
Organic acids and derivatives
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Alternative Parents
Tyrosine and derivatives / Phenylalanine and derivatives / Histidine and derivatives / Aspartic acid and derivatives / Isoleucine and derivatives / Valine and derivatives / Proline and derivatives / N-acyl-L-alpha-amino acids / Alpha amino acid amides / Phenylpropanoic acids
show 21 more
Alpha-oligopeptide / Tyrosine or derivatives / Phenylalanine or derivatives / Histidine or derivatives / Aspartic acid or derivatives / Isoleucine or derivatives / N-acyl-alpha-amino acid / N-acyl-alpha amino acid or derivatives / N-acyl-l-alpha-amino acid / Valine or derivatives
show 46 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
angiotensin II (CHEBI:2719) / Angiotensin [KO:K09821] (C02135)


Pharmacological action
General Function
Protein heterodimerization activity
Specific Function
Receptor for angiotensin II. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.
Gene Name
Uniprot ID
Uniprot Name
Type-1 angiotensin II receptor
Molecular Weight
41060.53 Da

Drug created on October 20, 2016 14:53 / Updated on June 12, 2020 10:53

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