Details
Stereochemistry | RACEMIC |
Molecular Formula | C21H27NO3 |
Molecular Weight | 341.444 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCCNCC(O)COC1=C(C=CC=C1)C(=O)CCC2=CC=CC=C2
InChI
InChIKey=JWHAUXFOSRPERK-UHFFFAOYSA-N
InChI=1S/C21H27NO3/c1-2-14-22-15-18(23)16-25-21-11-7-6-10-19(21)20(24)13-12-17-8-4-3-5-9-17/h3-11,18,22-23H,2,12-16H2,1H3
Molecular Formula | C21H27NO3 |
Molecular Weight | 341.444 |
Charge | 0 |
Count |
|
Stereochemistry | RACEMIC |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Optical Activity | ( + / - ) |
DescriptionCurator's Comment: description was created based on several sources, including
https://www.drugbank.ca/drugs/DB01182 | http://reference.medscape.com/drug/rythmol-propafenone-342307 | https://www.drugs.com/pro/propafenone.html | https://www.ncbi.nlm.nih.gov/pubmed/26588045
Curator's Comment: description was created based on several sources, including
https://www.drugbank.ca/drugs/DB01182 | http://reference.medscape.com/drug/rythmol-propafenone-342307 | https://www.drugs.com/pro/propafenone.html | https://www.ncbi.nlm.nih.gov/pubmed/26588045
Propafenone (brand name Rythmol SR or Rytmonorm) is a class 1C anti-arrhythmic medication, which treats illnesses associated with rapid heartbeats such as atrial and ventricular arrhythmias. The electrophysiological effect of propafenone manifests itself in a reduction of upstroke velocity (Phase 0) of the monophasic action potential. In Purkinje fibers, and to a lesser extent myocardial fibers, propafenone reduces the fast inward current carried by sodium ions, which is responsible for the drugs antiarrhythmic actions. Diastolic excitability threshold is increased and effective refractory period prolonged. Propafenone reduces spontaneous automaticity and depresses triggered activity. At very high concentrations in vitro, propafenone can inhibit the slow inward current carried by calcium but this calcium antagonist effect probably does not contribute to antiarrhythmic efficacy. Propafenone is metabolized primarily in the liver. Because of its short half-life, it requires dosing two or three times daily to maintain steady blood levels. The long-term safety of propafenone is unknown. Because it is structurally similar to another anti-arrhythmic medicine, flecainide, similar cautions should be exercised in its use. Flecainide and propafenone, like other antiarrhythmic drugs, have been shown to increase the occurrence of arrhythmias (5.3% for propafenone, Teva physician prescribing information), primarily in patients with underlying heart disease. However, their use in structurally normal hearts is considered safe.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2321615 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26588045 |
7.6 nM [IC50] | ||
Target ID: CHEMBL2321613 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26588045 |
5.1 µM [IC50] | ||
Target ID: CHEMBL1980 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21955244 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | RYTHMOL Approved UsePropafenone HCl Extended Release Capsules is indicated to prolong the time to recurrence of symptomatic atrial fibrillation (AF) in patients with episodic (most likely paroxysmal or persistent) AF who do not have structural heart disease. Usage Considerations: •The use of propafenone ER capsules in patients with permanent AF or in patients exclusively with atrial flutter or paroxysmal supraventricular tachycardia (PSVT) has not been evaluated. Do not use propafenone ER capsules to control ventricular rate during AF. •Some patients with atrial flutter treated with propafenone have developed 1:1 conduction, producing an increase in ventricular rate. Concomitant treatment with drugs that increase the functional atrioventricular (AV) nodal refractory period is recommended. • The effect of propafenone on mortality has not been determined [see BOXED WARNING Launch Date1989 |
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Primary | RYTHMOL Approved UsePropafenone HCl Extended Release Capsules is indicated to prolong the time to recurrence of symptomatic atrial fibrillation (AF) in patients with episodic (most likely paroxysmal or persistent) AF who do not have structural heart disease. Usage Considerations: •The use of propafenone ER capsules in patients with permanent AF or in patients exclusively with atrial flutter or paroxysmal supraventricular tachycardia (PSVT) has not been evaluated. Do not use propafenone ER capsules to control ventricular rate during AF. •Some patients with atrial flutter treated with propafenone have developed 1:1 conduction, producing an increase in ventricular rate. Concomitant treatment with drugs that increase the functional atrioventricular (AV) nodal refractory period is recommended. • The effect of propafenone on mortality has not been determined [see BOXED WARNING Launch Date1989 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
314 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3606933 |
300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered: |
PROPAFENONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
189.94 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19402341 |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
PROPAFENONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2900 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3606933 |
300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered: |
PROPAFENONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
322.43 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19402341 |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
PROPAFENONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3.61 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3606933 |
300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered: |
PROPAFENONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
4.1% EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/2753068 |
PROPAFENONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
425 mg 2 times / day multiple, oral Highest studied dose Dose: 425 mg, 2 times / day Route: oral Route: multiple Dose: 425 mg, 2 times / day Sources: |
unhealthy, adult n = 135 Health Status: unhealthy Condition: atrial fibrillation Age Group: adult Sex: M+F Population Size: 135 Sources: |
Other AEs: Monocyte count increased, Eosinophil count increased... Other AEs: Monocyte count increased (0.7%) Sources: Eosinophil count increased (0.7%) Platelet count decreased (0.7%) Cardiac failure congestive (1.5%) Coronary artery disease NOS (0.7%) Myocardial infarction (0.7%) Abdominal pain NOS (0.7%) Diarrhea NOS (0.7%) Chest pain (1.5%) Pneumonia NOS (0.7%) Urinary tract infection NOS (0.7%) Prothrombin level decreased (0.7%) Headache (0.7%) Syncope (0.7%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Abdominal pain NOS | 0.7% | 425 mg 2 times / day multiple, oral Highest studied dose Dose: 425 mg, 2 times / day Route: oral Route: multiple Dose: 425 mg, 2 times / day Sources: |
unhealthy, adult n = 135 Health Status: unhealthy Condition: atrial fibrillation Age Group: adult Sex: M+F Population Size: 135 Sources: |
Coronary artery disease NOS | 0.7% | 425 mg 2 times / day multiple, oral Highest studied dose Dose: 425 mg, 2 times / day Route: oral Route: multiple Dose: 425 mg, 2 times / day Sources: |
unhealthy, adult n = 135 Health Status: unhealthy Condition: atrial fibrillation Age Group: adult Sex: M+F Population Size: 135 Sources: |
Diarrhea NOS | 0.7% | 425 mg 2 times / day multiple, oral Highest studied dose Dose: 425 mg, 2 times / day Route: oral Route: multiple Dose: 425 mg, 2 times / day Sources: |
unhealthy, adult n = 135 Health Status: unhealthy Condition: atrial fibrillation Age Group: adult Sex: M+F Population Size: 135 Sources: |
Eosinophil count increased | 0.7% | 425 mg 2 times / day multiple, oral Highest studied dose Dose: 425 mg, 2 times / day Route: oral Route: multiple Dose: 425 mg, 2 times / day Sources: |
unhealthy, adult n = 135 Health Status: unhealthy Condition: atrial fibrillation Age Group: adult Sex: M+F Population Size: 135 Sources: |
Headache | 0.7% | 425 mg 2 times / day multiple, oral Highest studied dose Dose: 425 mg, 2 times / day Route: oral Route: multiple Dose: 425 mg, 2 times / day Sources: |
unhealthy, adult n = 135 Health Status: unhealthy Condition: atrial fibrillation Age Group: adult Sex: M+F Population Size: 135 Sources: |
Monocyte count increased | 0.7% | 425 mg 2 times / day multiple, oral Highest studied dose Dose: 425 mg, 2 times / day Route: oral Route: multiple Dose: 425 mg, 2 times / day Sources: |
unhealthy, adult n = 135 Health Status: unhealthy Condition: atrial fibrillation Age Group: adult Sex: M+F Population Size: 135 Sources: |
Myocardial infarction | 0.7% | 425 mg 2 times / day multiple, oral Highest studied dose Dose: 425 mg, 2 times / day Route: oral Route: multiple Dose: 425 mg, 2 times / day Sources: |
unhealthy, adult n = 135 Health Status: unhealthy Condition: atrial fibrillation Age Group: adult Sex: M+F Population Size: 135 Sources: |
Platelet count decreased | 0.7% | 425 mg 2 times / day multiple, oral Highest studied dose Dose: 425 mg, 2 times / day Route: oral Route: multiple Dose: 425 mg, 2 times / day Sources: |
unhealthy, adult n = 135 Health Status: unhealthy Condition: atrial fibrillation Age Group: adult Sex: M+F Population Size: 135 Sources: |
Pneumonia NOS | 0.7% | 425 mg 2 times / day multiple, oral Highest studied dose Dose: 425 mg, 2 times / day Route: oral Route: multiple Dose: 425 mg, 2 times / day Sources: |
unhealthy, adult n = 135 Health Status: unhealthy Condition: atrial fibrillation Age Group: adult Sex: M+F Population Size: 135 Sources: |
Prothrombin level decreased | 0.7% | 425 mg 2 times / day multiple, oral Highest studied dose Dose: 425 mg, 2 times / day Route: oral Route: multiple Dose: 425 mg, 2 times / day Sources: |
unhealthy, adult n = 135 Health Status: unhealthy Condition: atrial fibrillation Age Group: adult Sex: M+F Population Size: 135 Sources: |
Syncope | 0.7% | 425 mg 2 times / day multiple, oral Highest studied dose Dose: 425 mg, 2 times / day Route: oral Route: multiple Dose: 425 mg, 2 times / day Sources: |
unhealthy, adult n = 135 Health Status: unhealthy Condition: atrial fibrillation Age Group: adult Sex: M+F Population Size: 135 Sources: |
Urinary tract infection NOS | 0.7% | 425 mg 2 times / day multiple, oral Highest studied dose Dose: 425 mg, 2 times / day Route: oral Route: multiple Dose: 425 mg, 2 times / day Sources: |
unhealthy, adult n = 135 Health Status: unhealthy Condition: atrial fibrillation Age Group: adult Sex: M+F Population Size: 135 Sources: |
Cardiac failure congestive | 1.5% | 425 mg 2 times / day multiple, oral Highest studied dose Dose: 425 mg, 2 times / day Route: oral Route: multiple Dose: 425 mg, 2 times / day Sources: |
unhealthy, adult n = 135 Health Status: unhealthy Condition: atrial fibrillation Age Group: adult Sex: M+F Population Size: 135 Sources: |
Chest pain | 1.5% | 425 mg 2 times / day multiple, oral Highest studied dose Dose: 425 mg, 2 times / day Route: oral Route: multiple Dose: 425 mg, 2 times / day Sources: |
unhealthy, adult n = 135 Health Status: unhealthy Condition: atrial fibrillation Age Group: adult Sex: M+F Population Size: 135 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes [IC50 1 uM] | ||||
yes [IC50 19.9 uM] | ||||
yes [IC50 21.3 uM] | ||||
yes [IC50 6.8 uM] | ||||
yes [Ki 74.2 uM] | ||||
yes | ||||
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
yes | ||||
yes | yes (co-administration study) Comment: amiodarone and tobacco (CYP1A2 inhibitor) can be expected to cause increased plasma levels of propafenone |
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yes | yes (co-administration study) Comment: ketoconazole, erythromycin, saquinavir, and grapefruit juice for (CYP3A4 inhibitors) can be expected to cause increased plasma levels of propafenone; The combination of CYP3A4 inhibition and either CYP2D6 deficiency or CYP2D6 sinhibition with the simultaneous administration of propafenone may significantly increase the concentration of propafenone and thereby increase the risk of proarrhythmia and other adverse event |
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yes | yes (pharmacogenomic study) Comment: Multiple studies have found that genetic variants in the CYP2D6 gene influence the plasma drug levels of propafenone Sources: https://www.ncbi.nlm.nih.gov/books/NBK425391/ |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
An organic psychosis due to a venlafaxine-propafenone interaction. | 2001 |
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[Comparison of efficacy, safety and cost-effectiveness of intravenous versus oral propafenone in paroxysmal atrial fibrillation]. | 2001 Aug |
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Single oral loading dose of propafenone for pharmacological cardioversion of recent-onset atrial fibrillation. | 2001 Feb |
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Evaluation of CYP2D6 oxidation of dextromethorphan and propafenone in a Chinese population with atrial fibrillation. | 2001 Jan |
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Intravenous antiarrhythmic agents. | 2001 Jan |
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Efficacy of sequential antiarrhythmic treatment in sinus rhythm maintenance after successful electrocardioversion in patients with chronic non-valvular atrial fibrillation. | 2001 Jan-Feb |
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Global distribution of atrial ectopic foci triggering recurrence of atrial tachyarrhythmia after electrical cardioversion of long-standing atrial fibrillation: a bi-atrial basket mapping study. | 2001 Mar 1 |
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Giant inverted T waves. | 2001 Nov |
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Late-breaking clinical trials at the American Heart Association's scientific sessions 2001. | 2001 Nov 20 |
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Long-term efficacy and safety of propafenone and sotalol for the maintenance of sinus rhythm after conversion of recurrent symptomatic atrial fibrillation. | 2001 Sep 15 |
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Oral mucosal drug delivery: clinical pharmacokinetics and therapeutic applications. | 2002 |
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Risk of mortality in a cohort of patients newly diagnosed with chronic atrial fibrillation. | 2002 |
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Adverse drug events in hospitalized patients treated with cardiovascular drugs and anticoagulants. | 2002 Apr-May |
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Congenital junctional ectopic tachycardia in children and adolescents: a 20 year experience based study. | 2002 Aug |
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Efficacy and safety of propafenone sustained release in the prophylaxis of symptomatic paroxysmal atrial fibrillation (The European Rythmol/Rytmonorm Atrial Fibrillation Trial [ERAFT] Study). | 2002 Dec 15 |
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[Disclosure of "Brugada's syndrome" with intravenous propafenone]. | 2002 Jan-Mar |
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Propafenone-related cholestatic hepatitis in an elderly patient. | 2002 Jul |
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[The treatment of postoperative junctional ectopic tachycardia]. | 2002 Jun |
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Intermittent Brugada syndrome misdiagnosed as acute myocardial infarction and unmasked with propafenone. | 2002 Jun |
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Human variability in polymorphic CYP2D6 metabolism: is the kinetic default uncertainty factor adequate? | 2002 Nov |
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[Recent onset atrial fibrillation at a unit of internal medicine]. | 2002 Oct |
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New insights into the mechanisms and management of atrial fibrillation. | 2002 Oct 29 |
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Maintaining stability of sinus rhythm in atrial fibrillation: antiarrhythmic drugs versus ablation. | 2002 Sep |
|
High-throughput screening to estimate single or multiple enzymes involved in drug metabolism: microtitre plate assay using a combination of recombinant CYP2D6 and human liver microsomes. | 2003 Aug |
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Oral loading single dose flecainide for pharmacological cardioversion of recent-onset atrial fibrillation. | 2003 Feb |
|
A novel two-pore domain K+ channel, TRESK, is localized in the spinal cord. | 2003 Jul 25 |
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[Drug therapy of atrial fibrillation]. | 2003 Jun 15 |
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Propafenone versus ibutilide for post operative atrial fibrillation following cardiac surgery: neither strategy improves outcomes compared to rate control alone (the PIPAF study). | 2003 Mar |
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In silico screening with benzofurane- and benzopyrane-type MDR-modulators. | 2003 Mar |
Patents
Sample Use Guides
Initiate therapy with 150 mg given every 8 hours.
As needed, uptitrate in 3-4 days to 225-300 mg every 8 hours
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24385693
Hela cells were used for activity evaluation. Proliferation percentage was determined by the SRB assay. Cells were incubated with the Propafenone at the concentrations of 0.005-0.2 g/L for 48 h, and the cell proliferation/viability was determined using the survival percentage with the cells treated only with dimethyl sulfoxide (DMSO) at 0.1% as a reference
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 15:30:38 GMT 2023
by
admin
on
Fri Dec 15 15:30:38 GMT 2023
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Record UNII |
68IQX3T69U
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Record Status |
Validated (UNII)
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Record Version |
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NCI_THESAURUS |
C93038
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LIVERTOX |
NBK548005
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NDF-RT |
N0000175426
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NCI_THESAURUS |
C47793
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WHO-VATC |
QC01BC03
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WHO-ATC |
C01BC03
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DTXSID9045184
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DB01182
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2561
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2291
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258-955-6
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PROPAFENONE
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CHEMBL631
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68IQX3T69U
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Propafenone
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4932
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54063-53-5
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100000081149
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63619
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m9178
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D011405
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C61909
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68IQX3T69U
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SUB10094MIG
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Related Record | Type | Details | ||
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TRANSPORTER -> INHIBITOR | |||
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BINDER->LIGAND | |||
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METABOLIC ENZYME -> INHIBITOR |
IC50
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SALT/SOLVATE -> PARENT |
Related Record | Type | Details | ||
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METABOLITE ACTIVE -> PARENT | |||
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METABOLITE ACTIVE -> PARENT | |||
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METABOLITE ACTIVE -> PARENT |
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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Elimination PHARMACOKINETIC PHARMACOKINETIC |
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Volume of Distribution | PHARMACOKINETIC |
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Population PHARMACOKINETIC |
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