Identification

Name
Candesartan cilexetil
Accession Number
DB00796  (APRD00420)
Type
Small Molecule
Groups
Approved
Description

Candesartan is an angiotensin-receptor blocker (ARB) that may be used alone or with other agents to treat hypertension. It is administered orally as the prodrug, candesartan cilexetil, which is rapidly converted to its active metabolite, candesartan, during absorption in the gastrointestinal tract. Candesartan lowers blood pressure by antagonizing the renin-angiotensin-aldosterone system (RAAS); it competes with angiotensin II for binding to the type-1 angiotensin II receptor (AT1) subtype and prevents the blood pressure increasing effects of angiotensin II. Unlike angiotensin-converting enzyme (ACE) inhibitors, ARBs do not have the adverse effect of dry cough. Candesartan may be used to treat hypertension, isolated systolic hypertension, left ventricular hypertrophy and diabetic nephropathy. It may also be used as an alternative agent for the treatment of heart failure, systolic dysfunction, myocardial infarction and coronary artery disease.

Structure
Thumb
Synonyms
Not Available
External IDs
TCV 116 / TCV-116
Active Moieties
NameKindUNIICASInChI Key
CandesartanprodrugS8Q36MD2XX139481-59-7HTQMVQVXFRQIKW-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act CandesartanTablet8 mgOralActavis Pharma Company2011-11-30Not applicableCanada
Act CandesartanTablet32 mgOralActavis Pharma Company2011-11-30Not applicableCanada
Act CandesartanTablet4 mgOralActavis Pharma Company2011-11-30Not applicableCanada
Act CandesartanTablet16 mgOralActavis Pharma Company2011-12-15Not applicableCanada
AtacandTablet32 mgOralAstra Zeneca2008-07-17Not applicableCanada
AtacandTablet8 mg/1OralAstra Zeneca Lp1998-09-14Not applicableUs00186 0008 31 nlmimage10 083a0400
AtacandTablet4 mgOralAstra Zeneca2005-06-28Not applicableCanada
AtacandTablet16 mg/1OralCardinal Health2009-11-112015-04-30Us55154 961020180913 8702 bp0sg0
AtacandTablet4 mg/1OralCarilion Materials Management1998-09-14Not applicableUs
AtacandTablet16 mg/1OralPhysicians Total Care, Inc.2000-11-21Not applicableUs00186 0016 54 nlmimage10 f812fc37
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Accel-candesartanTablet8 mgOralAccel Pharma Inc2017-12-27Not applicableCanada
Accel-candesartanTablet32 mgOralAccel Pharma Inc2017-12-27Not applicableCanada
Accel-candesartanTablet16 mgOralAccel Pharma Inc2017-12-27Not applicableCanada
Accel-candesartanTablet4 mgOralAccel Pharma IncNot applicableNot applicableCanada
Ach-candesartanTablet16 mgOralAccord Healthcare Limited2012-02-16Not applicableCanada
Ach-candesartanTablet8 mgOralAccord Healthcare Limited2012-02-16Not applicableCanada
Ach-candesartanTablet4 mgOralAccord Healthcare Limited2012-02-16Not applicableCanada
Ach-candesartanTablet32 mgOralAccord Healthcare Limited2012-02-16Not applicableCanada
Apo-candesartanTablet8 mgOralApotex Corporation2011-04-26Not applicableCanada
Apo-candesartanTablet32 mgOralApotex Corporation2013-07-16Not applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Accel-candesartan/hctzCandesartan cilexetil (16 mg) + Hydrochlorothiazide (12.5 mg)TabletOralAccel Pharma Inc2017-12-27Not applicableCanada
Accel-candesartan/hctzCandesartan cilexetil (32 mg) + Hydrochlorothiazide (25 mg)TabletOralAccel Pharma Inc2017-12-27Not applicableCanada
Accel-candesartan/hctzCandesartan cilexetil (32 mg) + Hydrochlorothiazide (12.5 mg)TabletOralAccel Pharma Inc2017-12-27Not applicableCanada
Act Candesartan/hctCandesartan cilexetil (16 mg) + Hydrochlorothiazide (12.5 mg)TabletOralActavis Pharma Company2012-09-24Not applicableCanada
Apo-candesartan/hctzCandesartan cilexetil (32 mg) + Hydrochlorothiazide (12.5 mg)TabletOralApotex Corporation2013-03-04Not applicableCanada
Apo-candesartan/hctzCandesartan cilexetil (16.0 mg) + Hydrochlorothiazide (12.5 mg)TabletOralApotex Corporation2012-09-25Not applicableCanada
Apo-candesartan/hctzCandesartan cilexetil (32 mg) + Hydrochlorothiazide (25 mg)TabletOralApotex Corporation2013-03-04Not applicableCanada
Atacand HCTCandesartan cilexetil (32 mg/1) + Hydrochlorothiazide (12.5 mg/1)TabletOralPhysicians Total Care, Inc.2003-11-13Not applicableUs00186 0322 54 nlmimage10 f512fae7
Atacand HCTCandesartan cilexetil (16 mg/1) + Hydrochlorothiazide (12.5 mg/1)TabletOralAstra Zeneca Lp2000-09-28Not applicableUs0186 016220180907 15195 1c9x1u
Atacand HCTCandesartan cilexetil (16 mg/1) + Hydrochlorothiazide (12.5 mg/1)TabletOralPhysicians Total Care, Inc.2003-01-21Not applicableUs00186 0162 54 nlmimage10 e912f487
International/Other Brands
Amias (Eureco (Netherlands), Takeda (United Kingdom)) / Blopress (Takeda)
Categories
UNII
R85M2X0D68
CAS number
145040-37-5
Weight
Average: 610.671
Monoisotopic: 610.253982839
Chemical Formula
C33H34N6O6
InChI Key
GHOSNRCGJFBJIB-UHFFFAOYSA-N
InChI
InChI=1S/C33H34N6O6/c1-3-42-32-34-28-15-9-14-27(31(40)43-21(2)44-33(41)45-24-10-5-4-6-11-24)29(28)39(32)20-22-16-18-23(19-17-22)25-12-7-8-13-26(25)30-35-37-38-36-30/h7-9,12-19,21,24H,3-6,10-11,20H2,1-2H3,(H,35,36,37,38)
IUPAC Name
1-{[(cyclohexyloxy)carbonyl]oxy}ethyl 2-ethoxy-1-{[2'-(1H-1,2,3,4-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl]methyl}-1H-1,3-benzodiazole-7-carboxylate
SMILES
CCOC1=NC2=C(N1CC1=CC=C(C=C1)C1=CC=CC=C1C1=NN=NN1)C(=CC=C2)C(=O)OC(C)OC(=O)OC1CCCCC1

Pharmacology

Indication

May be used as a first line agent to treat uncomplicated hypertension, isolated systolic hypertension and left ventricular hypertrophy. May be used as a first line agent to delay progression of diabetic nephropathy. Candesartan may be also used as a second line agent in the treatment of congestive heart failure, systolic dysfunction, myocardial infarction and coronary artery disease in those intolerant of ACE inhibitors.

Associated Conditions
Pharmacodynamics

Candesartan cilexetil is an ARB prodrug that is rapidly converted to candesartan, its active metabolite, during absorption from the gastrointestinal tract. Candesartan confers blood pressure lowering effects by antagonizing the hypertensive effects of angiotensin II via the RAAS. RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from granular cells of the juxtaglomerular apparatus in the kidneys. Renin cleaves circulating angiotensinogen to angiotensin I, which is cleaved by angiotensin converting enzyme (ACE) to angiotensin II. Angiotensin II increases blood pressure by increasing total peripheral resistance, increasing sodium and water reabsorption in the kidneys via aldosterone secretion, and altering cardiovascular structure. Angiotensin II binds to two receptors: type-1 angiotensin II receptor (AT1) and type-2 angiotensin II receptor (AT2). AT1 is a G-protein coupled receptor (GPCR) that mediates the vasoconstrictive and aldosterone-secreting effects of angiotensin II. Studies performed in recent years suggest that AT2 antagonizes AT1-mediated effects and directly affects long-term blood pressure control by inducing vasorelaxation and increasing urinary sodium excretion. Angiotensin receptor blockers (ARBs) are non-peptide competitive inhibitors of AT1. ARBs block the ability of angiotensin II to stimulate pressor and cell proliferative effects. Unlike ACE inhibitors, ARBs do not affect bradykinin-induced vasodilation. The overall effect of ARBs is a decrease in blood pressure.

Mechanism of action

Candesartan selectively blocks the binding of angiotensin II to AT1 in many tissues including vascular smooth muscle and the adrenal glands. This inhibits the AT1-mediated vasoconstrictive and aldosterone-secreting effects of angiotensin II and results in an overall decrease in blood pressure. Candesartan is greater than 10,000 times more selective for AT1 than AT2. Inhibition of aldosterone secretion may increase sodium and water excretion while decreasing potassium excretion.

TargetActionsOrganism
AType-1 angiotensin II receptor
antagonist
Human
Absorption

Following administration of the candesartan cilexetil prodrug, the absolute bioavailability of candesartan was estimated to be 15%. Food with a high fat content has no effect on the bioavailability of candesartan from candesartan cilexetil.

Volume of distribution
  • 0.13 L/kg
Protein binding

Candesartan is highly bound to plasma proteins (>99%) and does not penetrate red blood cells.

Metabolism

The prodrug candesartan cilexetil undergoes rapid and complete ester hydrolysis in the intestinal wall to form the active drug, candesartan. Elimination of candesartan is primarily as unchanged drug in the urine and, by the biliary route, in the feces. Minor hepatic metabolism of candesartan (<20%) occurs by O-deethylation via cytochrome P450 2C9 to form an inactive metabolite. Candesartan undergoes N-glucuronidation in the tetrazole ring by uridine diphosphate glucuronosyltransferase 1A3 (UGT1A3). O-glucuronidation may also occur. 75% of candesartan is excreted as unchanged drug in urine and feces.

Route of elimination

When candesartan is administered orally, about 26% of the dose is excreted unchanged in urine. Candesartan is mainly excreted unchanged in urine and feces (via bile).

Half life

Approximately 9 hours.

Clearance
  • 0.37 mL/min/kg
Toxicity

No lethality was observed in acute toxicity studies in mice, rats and dogs given single oral doses of up to 2000 mg/kg of candesartan cilexetil or in rats given single oral doses of up to 2000 mg/kg of candesartan cilexetil in combination with 1000 mg/kg of hydrochlorothiazide. In mice given single oral doses of the primary metabolite, candesartan, the minimum lethal dose was greater than 1000 mg/kg but less than 2000 mg/kg.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Candesartan Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(4R)-limoneneThe risk or severity of adverse effects can be increased when Candesartan cilexetil is combined with (4R)-limonene.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypotensive activities of Candesartan cilexetil.
AbirateroneThe metabolism of Candesartan cilexetil can be decreased when combined with Abiraterone.
AcebutololCandesartan cilexetil may increase the hypotensive activities of Acebutolol.
AceclofenacThe risk or severity of adverse effects can be increased when Candesartan cilexetil is combined with Aceclofenac.
AcemetacinThe therapeutic efficacy of Candesartan cilexetil can be decreased when used in combination with Acemetacin.
AcetazolamideThe risk or severity of hypotension can be increased when Candesartan cilexetil is combined with Acetazolamide.
Acetyl sulfisoxazoleThe metabolism of Candesartan cilexetil can be decreased when combined with Acetyl sulfisoxazole.
Acetylsalicylic acidThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Candesartan cilexetil is combined with Acetylsalicylic acid.
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Candesartan cilexetil.
Food Interactions
  • Administer on a regular basis, at about the same time each day.
  • Take without regard to meals.

References

Synthesis Reference

Marina Etinger, Boris Fedotev, Ben-Zion Dolitzky, "Preparation of candesartan cilexetil." U.S. Patent US20050131037, issued June 16, 2005.

US20050131037
General References
  1. Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J, Yusuf S, Pocock S: Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet. 2003 Sep 6;362(9386):759-66. [PubMed:13678868]
  2. Mendis B, Page SR: Candesartan: widening indications for this angiotensin II receptor blocker? Expert Opin Pharmacother. 2009 Aug;10(12):1995-2007. doi: 10.1517/14656560903092197. [PubMed:19563275]
  3. Baguet JP, Barone-Rochette G, Neuder Y: Candesartan cilexetil in the treatment of chronic heart failure. Vasc Health Risk Manag. 2009;5(1):257-64. Epub 2009 Apr 8. [PubMed:19436650]
  4. Stanfield, Cindy L.;Germann, William J. (2009). Principles of Human Physiology (3rd ed.). Benjamin-Cummings Publishing Company. [ISBN:978-0321556660]
  5. Bader, M. (2004). Renin-angiotensin-aldosterone system. In Encyclopedic reference of molecular pharmacology (pp. 810-814). Berlin: Springer. [ISBN:9783540298328]
External Links
KEGG Drug
D00626
PubChem Compound
2540
PubChem Substance
46508342
ChemSpider
2444
BindingDB
50318907
ChEBI
3348
ChEMBL
CHEMBL1014
Therapeutic Targets Database
DAP001442
IUPHAR
587
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Candesartan
AHFS Codes
  • 24:32.08 — Angiotensin Ii Receptor Antagonists
FDA label
Download (49.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedBasic ScienceEsophagus, Barrett1
1Active Not RecruitingOtherMethamphetamine Abuse / Methamphetamine Dependence / Substance Abuse1
1Active Not RecruitingTreatmentHealthy Male Subjects1
1CompletedNot AvailableHealthy Volunteers1
1CompletedNot AvailableHypertension,Essential1
1CompletedBasic ScienceHigh Blood Pressure (Hypertension)1
1CompletedOtherCardiovascular Disease (CVD) / Respiratory Disorders1
1CompletedTreatmentChronic Kidney Disease (CKD) / Hyperphosphataemia1
1CompletedTreatmentHealthy Volunteers4
1CompletedTreatmentHigh Blood Pressure (Hypertension)8
1CompletedTreatmentHypertension,Essential1
1Not Yet RecruitingNot AvailableHealthy Male Subjects1
1Not Yet RecruitingTreatmentHigh Blood Pressure (Hypertension)1
1Unknown StatusBasic ScienceHealthy Volunteers1
1, 2Active Not RecruitingTreatmentCardiorenal Syndrome (CRS)1
2CompletedPreventionCancer, Breast / Heart Failure, Unspecified1
2CompletedTreatmentAging / Cognitive Impairments / High Blood Pressure (Hypertension)1
2CompletedTreatmentBMI >30 kg/m2 / High Blood Pressure (Hypertension)1
2CompletedTreatmentCluster Headache1
2CompletedTreatmentDependence, Cocaine1
2CompletedTreatmentHypertension,Essential3
2CompletedTreatmentType 2 Diabetes Mellitus and Microalbuminuria1
2Not Yet RecruitingTreatmentHigh Blood Pressure (Hypertension)1
2RecruitingTreatmentHypertension,Essential1
2RecruitingTreatmentMild Cognitive Impairment (MCI)1
2Unknown StatusNot AvailableHypertrophic Cardiomyopathy1
2Unknown StatusTreatmentHypertension,Essential1
2WithdrawnTreatmentHepatitis C Viral Infection1
2, 3CompletedTreatmentChronic Migraine / Migraine With Aura / Migraine Without Aura1
2, 3CompletedTreatmentDiabetes Mellitus (DM)1
3Active Not RecruitingPreventionHigh Blood Pressure (Hypertension) / Mild Cognitive Impairment (MCI)1
3CompletedPreventionAtherosclerosis / Cardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Diabetes Mellitus (DM) / High Blood Pressure (Hypertension) / High Cholesterol / Type 2 Diabetes Mellitus1
3CompletedPreventionHigh Blood Pressure (Hypertension)1
3CompletedTreatmentCancer, Breast1
3CompletedTreatmentCholesterolemia / High Blood Pressure (Hypertension)1
3CompletedTreatmentCongestive Heart Failure (CHF)3
3CompletedTreatmentDiabetes, Diabetes Mellitus Type 12
3CompletedTreatmentHeart Failure, Unspecified1
3CompletedTreatmentHigh Blood Pressure (Hypertension)6
3CompletedTreatmentNonvalvular Atrial Fibrillation1
3CompletedTreatmentProteinuria1
3CompletedTreatmentStrokes1
3CompletedTreatmentType 2 Diabetes Mellitus1
3RecruitingTreatmentHigh Blood Pressure (Hypertension)1
3TerminatedTreatmentHeart Failure, Unspecified1
3Unknown StatusNot AvailableHigh Blood Pressure (Hypertension)1
3Unknown StatusTreatmentAortic Valve Stenosis1
3Unknown StatusTreatmentAortic Valve Stenosis / Left Ventricular Hypertrophy / Nonvalvular Atrial Fibrillation1
3Unknown StatusTreatmentCardiovascular Disease (CVD) / High Blood Pressure (Hypertension)1
3Unknown StatusTreatmentHypertension,Essential2
3WithdrawnTreatmentEssential Arterial Hypertension2
3WithdrawnTreatmentHigh Blood Pressure (Hypertension)1
4Active Not RecruitingTreatmentAcute Heart Failure (AHF)1
4CompletedOtherBMI >30 kg/m2 / High Blood Pressure (Hypertension) / Resistant Hypertension / White Coat Hypertension1
4CompletedPreventionCardiovascular Disease (CVD) / Strokes1
4CompletedPreventionCoronary Artery Disease / High Blood Pressure (Hypertension)1
4CompletedScreeningChronic Kidney Disease (CKD) / High Blood Pressure (Hypertension) / Proteinuria1
4CompletedTreatmentAngiotensin Converting Enzyme / Angiotensin Receptor Blockers / Cardiopulmonary Bypass / Coronary Artery Disease / Fibrinolysis / Inflammatory Reaction1
4CompletedTreatmentBMI >30 kg/m2 / High Blood Pressure (Hypertension)2
4CompletedTreatmentCardiovascular Disease (CVD) / Chronic Kidney Disease (CKD) / Hypertension,Essential / Strokes1
4CompletedTreatmentCongestive Heart Failure (CHF) / High Blood Pressure (Hypertension)1
4CompletedTreatmentHealthy Volunteers1
4CompletedTreatmentHeart Failure, Unspecified1
4CompletedTreatmentHeart Failure, Unspecified / Ventricular Dysfunction, Left1
4CompletedTreatmentHigh Blood Pressure (Hypertension)3
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Left Ventricular Hypertrophy1
4CompletedTreatmentMitral Valve Insufficiency1
4CompletedTreatmentNon-diabetic Nephropathy With Hypertension1
4CompletedTreatmentStage II Hypertension1
4Not Yet RecruitingTreatmentHigh Blood Pressure (Hypertension)1
4RecruitingPreventionBlood Pressures / High Blood Pressure (Hypertension) / Strokes1
4TerminatedBasic ScienceDepression / High Blood Pressure (Hypertension)1
4TerminatedTreatmentBMI >30 kg/m2 / Glucose tolerance impaired1
4Unknown StatusEducational/Counseling/TrainingType 2 Diabetes Mellitus1
4Unknown StatusTreatmentAutosomal Dominant Polycystic Kidney Disease (ADPKD)1
4Unknown StatusTreatmentCardiovascular Disease (CVD) / Chronic Renal Failure (CRF)1
4Unknown StatusTreatmentCerebrovascular Accidents / Stroke, Acute1
4Unknown StatusTreatmentHigh Blood Pressure (Hypertension)1
4Unknown StatusTreatmentHigh Blood Pressure (Hypertension) / Human Immunodeficiency Virus (HIV) Infections1
4Unknown StatusTreatmentHypertension,Essential1
4Unknown StatusTreatmentType I Diabetes1
Not AvailableCompletedNot AvailableCardiovascular Disease (CVD) / Heart Diseases / High Blood Pressure (Hypertension)1
Not AvailableCompletedNot AvailableCohort Study / Heart Failure, Unspecified1
Not AvailableCompletedNot AvailableHigh Blood Pressure (Hypertension)3
Not AvailableCompletedPreventionDiabetes, Diabetes Mellitus Type 1 / Hypoglycemia1
Not AvailableCompletedTreatmentDiabetic Nephropathies / High Blood Pressure (Hypertension)1
Not AvailableRecruitingNot AvailableObesity, Morbid1
Not AvailableTerminatedPreventionAcute Coronary Syndromes (ACS) / Acute Myocardial Infarction (AMI) / Angina Pectoris / High Blood Pressure (Hypertension) / Myocardial Ischemia1
Not AvailableUnknown StatusTreatmentHigh Blood Pressure (Hypertension)2

Pharmacoeconomics

Manufacturers
  • Astrazeneca pharmaceuticals lp
Packagers
  • A-S Medication Solutions LLC
  • AstraZeneca Inc.
  • Bryant Ranch Prepack
  • Lake Erie Medical and Surgical Supply
  • Physicians Total Care Inc.
  • Prepak Systems Inc.
  • Resource Optimization and Innovation LLC
  • Southwood Pharmaceuticals
Dosage forms
FormRouteStrength
TabletOral16 mg/1
TabletOral32 mg/1
TabletOral32 mg
TabletOral4 mg
TabletOral4 mg/1
TabletOral8 mg/1
TabletOral
TabletOral16 mg
TabletOral8 mg
Prices
Unit descriptionCostUnit
Atacand 30 4 mg tablet Bottle75.98USD bottle
Atacand 30 8 mg tablet Bottle74.96USD bottle
Atacand hct 32-25 mg tablet3.64USD tablet
Atacand hct 32-12.5 mg tablet3.43USD tablet
Atacand 32 mg tablet3.36USD tablet
Atacand hct 16-12.5 mg tablet3.36USD tablet
Atacand 16 mg tablet2.49USD tablet
Atacand 4 mg tablet2.44USD tablet
Atacand 8 mg tablet2.44USD tablet
Atacand 16 mg Tablet1.28USD tablet
Atacand 32 mg Tablet1.28USD tablet
Atacand 8 mg Tablet1.28USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5534534No1994-01-092014-01-09Us
US5705517No1994-04-182011-04-18Us
CA2083305No2003-12-092012-11-19Canada
CA2040955No1998-02-032011-04-22Canada

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP6.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00204 mg/mLALOGPS
logP5.12ALOGPS
logP7.53ChemAxon
logS-5.5ALOGPS
pKa (Strongest Acidic)4.23ChemAxon
pKa (Strongest Basic)1.45ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area143.34 Å2ChemAxon
Rotatable Bond Count13ChemAxon
Refractivity177.42 m3·mol-1ChemAxon
Polarizability63.94 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.8717
Caco-2 permeable-0.6208
P-glycoprotein substrateSubstrate0.5186
P-glycoprotein inhibitor INon-inhibitor0.848
P-glycoprotein inhibitor IINon-inhibitor0.9115
Renal organic cation transporterNon-inhibitor0.8266
CYP450 2C9 substrateNon-substrate0.7397
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.6504
CYP450 1A2 substrateInhibitor0.5594
CYP450 2C9 inhibitorInhibitor0.5195
CYP450 2D6 inhibitorNon-inhibitor0.889
CYP450 2C19 inhibitorInhibitor0.5151
CYP450 3A4 inhibitorInhibitor0.7392
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7895
Ames testAMES toxic0.556
CarcinogenicityNon-carcinogens0.7561
BiodegradationNot ready biodegradable0.9972
Rat acute toxicity2.5515 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.794
hERG inhibition (predictor II)Non-inhibitor0.5837
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
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

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
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
AGTR1
Uniprot ID
P30556
Uniprot Name
Type-1 angiotensin II receptor
Molecular Weight
41060.53 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Cervenka L, Navar LG: Renal responses of the nonclipped kidney of two-kidney/one-clip Goldblatt hypertensive rats to type 1 angiotensin II receptor blockade with candesartan. J Am Soc Nephrol. 1999 Jan;10 Suppl 11:S197-201. [PubMed:9892163]
  3. Malmqvist K, Kahan T, Dahl M: Angiotensin II type 1 (AT1) receptor blockade in hypertensive women: benefits of candesartan cilexetil versus enalapril or hydrochlorothiazide. Am J Hypertens. 2000 May;13(5 Pt 1):504-11. [PubMed:10826401]
  4. Wada T, Inada Y, Ojima M, Sanada T, Shibouta Y, Nishikawa K: Comparison of the antihypertensive effects of the new angiotensin II (AT1) receptor antagonist candesartan cilexetil (TCV-116) and the angiotensin converting enzyme inhibitor enalapril in rats. Hypertens Res. 1996 Jun;19(2):75-81. [PubMed:10968199]
  5. Engelhorn T, Doerfler A, Heusch G, Schulz R: Reduction of cerebral infarct size by the AT1-receptor blocker candesartan, the HMG-CoA reductase inhibitor rosuvastatin and their combination. An experimental study in rats. Neurosci Lett. 2006 Oct 2;406(1-2):92-6. Epub 2006 Aug 9. [PubMed:16901636]
  6. Caballero-George C, Vanderheyden PM, Solis PN, Gupta MP, Pieters L, Vauquelin G, Vlietinck A: In vitro effect of sanguinarine alkaloid on binding of [3H]candesartan to the human angiotensin AT1 receptor. Eur J Pharmacol. 2003 Jan 5;458(3):257-62. [PubMed:12504781]
  7. McInnes GT, O'Kane KP, Istad H, Keinanen-Kiukaanniemi S, Van Mierlo HF: Comparison of the AT1-receptor blocker, candesartan cilexetil, and the ACE inhibitor, lisinopril, in fixed combination with low dose hydrochlorothiazide in hypertensive patients. J Hum Hypertens. 2000 Apr;14(4):263-9. [PubMed:10805052]
  8. Vauquelin G, Fierens F, Van Liefde I: Long-lasting angiotensin type 1 receptor binding and protection by candesartan: comparison with other biphenyl-tetrazole sartans. J Hypertens Suppl. 2006 Mar;24(1):S23-30. [PubMed:16601569]
  9. Mendis B, Page SR: Candesartan: widening indications for this angiotensin II receptor blocker? Expert Opin Pharmacother. 2009 Aug;10(12):1995-2007. doi: 10.1517/14656560903092197. [PubMed:19563275]
  10. Meredith PA: Candesartan cilexetil--a review of effects on cardiovascular complications in hypertension and chronic heart failure. Curr Med Res Opin. 2007 Jul;23(7):1693-705. [PubMed:17588300]
  11. Baguet JP, Barone-Rochette G, Neuder Y: Candesartan cilexetil in the treatment of chronic heart failure. Vasc Health Risk Manag. 2009;5(1):257-64. Epub 2009 Apr 8. [PubMed:19436650]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. McClellan KJ, Goa KL: Candesartan cilexetil. A review of its use in essential hypertension. Drugs. 1998 Nov;56(5):847-69. [PubMed:9829158]
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. [PubMed:15601807]
  2. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [PubMed:26721703]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A3
Uniprot ID
P35503
Uniprot Name
UDP-glucuronosyltransferase 1-3
Molecular Weight
60337.835 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Takara K, Kakumoto M, Tanigawara Y, Funakoshi J, Sakaeda T, Okumura K: Interaction of digoxin with antihypertensive drugs via MDR1. Life Sci. 2002 Feb 15;70(13):1491-500. [PubMed:11895100]

Drug created on June 13, 2005 07:24 / Updated on September 25, 2018 17:45