U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C21H24N4O2S
Molecular Weight 396.5077
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MIRABEGRON

SMILES

c1ccc(cc1)[C@]([H])(CNCCc2ccc(cc2)NC(=O)Cc3csc(=N)[nH]3)O

InChI

InChIKey=PBAPPPCECJKMCM-IBGZPJMESA-N
InChI=1S/C21H24N4O2S/c22-21-25-18(14-28-21)12-20(27)24-17-8-6-15(7-9-17)10-11-23-13-19(26)16-4-2-1-3-5-16/h1-9,14,19,23,26H,10-13H2,(H2,22,25)(H,24,27)/t19-/m0/s1

HIDE SMILES / InChI

Molecular Formula C21H24N4O2S
Molecular Weight 396.5077
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/?term=20878594

Mirabegron (trade name Myrbetriq in the US and Betmiga in Europe) is a drug for the treatment of overactive bladder (OAB). It was developed by Astellas Pharma and was approved in the United States in July 2012. Originally developed as a treatment for diabetes, the development of mirabegron was later refocused to OAB. Mirabegron is an orally bioavailable agonist of the human beta-3 adrenergic receptor (ADRB3), with muscle relaxing, neuroprotective and potential antineoplastic activities. Upon oral administration, mirabegron binds to and activates ADRB3, which leads to smooth muscle relaxation. Mirabegron also restores sympathetic stimulation in mesenchymal stem cell (MSC) niches, inhibits JAK2-mutated hematopoietic stem cell (HSC) expansion and blocks the progression of myeloproliferative neoplasms (MPNs). Lack of sympathetic stimulation of the MSC and HSC niche is associated with the development of MPNs.

CNS Activity

Curator's Comment:: Mirabegron has a low propensity to cross the blood–brain barrier

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
22.4 nM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
MYRBETRIQ

Approved Use

Indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency.

Launch Date

1.34084166E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
12.8 ng/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MIRABEGRON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
29.4 ng/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MIRABEGRON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
177 ng × h/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MIRABEGRON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
46.82 ng × h/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MIRABEGRON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
41.5 h
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MIRABEGRON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
28.1 h
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MIRABEGRON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
29%
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MIRABEGRON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
200 mg 1 times / day multiple, oral
Studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
healthy, 23.6 years (range: 20–27 years)
n = 8
Health Status: healthy
Age Group: 23.6 years (range: 20–27 years)
Sex: M
Population Size: 8
Sources:
Other AEs: Pulse rate increased...
400 mg single, oral
Highest studied dose
Dose: 400 mg
Route: oral
Route: single
Dose: 400 mg
Sources:
healthy, 23.8 years (range: 20–27 years)
n = 6
Health Status: healthy
Age Group: 23.8 years (range: 20–27 years)
Sex: M
Population Size: 6
Sources:
200 mg 1 times / day multiple, oral
Studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
unhealthy, 58.0±13.7 years
n = 167
Health Status: unhealthy
Condition: overactive bladder
Age Group: 58.0±13.7 years
Sex: M+F
Population Size: 167
Sources:
Other AEs: Cardiac disorders, Eye disorders...
Other AEs:
Cardiac disorders (3%)
Eye disorders (3.6%)
Constipation (1.8%)
Dyspepsia (2.4%)
Sources:
25 mg 1 times / day steady, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: steady
Dose: 25 mg, 1 times / day
Sources: Page: p. 300
unhealthy, adult
n = 2736
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 2736
Sources: Page: p. 300
Disc. AE: Constipation, Hypertension...
AEs leading to
discontinuation/dose reduction:
Constipation (0.2%)
Hypertension (0.2%)
Tachycardia (0.1%)
Atrial fibrillation (0.5%)
Palpitations (0.5%)
Edema peripheral (0.5%)
Pyrexia (0.5%)
ALT increased (0.4%)
AST increased (0.4%)
Bilirubin increased (0.4%)
Liver enzyme abnormal (0.4%)
Hypertensive crisis (0.3%)
Sources: Page: p. 300
AEs

AEs

AESignificanceDosePopulation
Pulse rate increased 2%
200 mg 1 times / day multiple, oral
Studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
healthy, 23.6 years (range: 20–27 years)
n = 8
Health Status: healthy
Age Group: 23.6 years (range: 20–27 years)
Sex: M
Population Size: 8
Sources:
Constipation 1.8%
200 mg 1 times / day multiple, oral
Studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
unhealthy, 58.0±13.7 years
n = 167
Health Status: unhealthy
Condition: overactive bladder
Age Group: 58.0±13.7 years
Sex: M+F
Population Size: 167
Sources:
Dyspepsia 2.4%
200 mg 1 times / day multiple, oral
Studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
unhealthy, 58.0±13.7 years
n = 167
Health Status: unhealthy
Condition: overactive bladder
Age Group: 58.0±13.7 years
Sex: M+F
Population Size: 167
Sources:
Cardiac disorders 3%
200 mg 1 times / day multiple, oral
Studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
unhealthy, 58.0±13.7 years
n = 167
Health Status: unhealthy
Condition: overactive bladder
Age Group: 58.0±13.7 years
Sex: M+F
Population Size: 167
Sources:
Eye disorders 3.6%
200 mg 1 times / day multiple, oral
Studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
unhealthy, 58.0±13.7 years
n = 167
Health Status: unhealthy
Condition: overactive bladder
Age Group: 58.0±13.7 years
Sex: M+F
Population Size: 167
Sources:
Tachycardia 0.1%
Disc. AE
25 mg 1 times / day steady, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: steady
Dose: 25 mg, 1 times / day
Sources: Page: p. 300
unhealthy, adult
n = 2736
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 2736
Sources: Page: p. 300
Constipation 0.2%
Disc. AE
25 mg 1 times / day steady, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: steady
Dose: 25 mg, 1 times / day
Sources: Page: p. 300
unhealthy, adult
n = 2736
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 2736
Sources: Page: p. 300
Hypertension 0.2%
Disc. AE
25 mg 1 times / day steady, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: steady
Dose: 25 mg, 1 times / day
Sources: Page: p. 300
unhealthy, adult
n = 2736
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 2736
Sources: Page: p. 300
Hypertensive crisis 0.3%
Disc. AE
25 mg 1 times / day steady, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: steady
Dose: 25 mg, 1 times / day
Sources: Page: p. 300
unhealthy, adult
n = 2736
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 2736
Sources: Page: p. 300
ALT increased 0.4%
Disc. AE
25 mg 1 times / day steady, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: steady
Dose: 25 mg, 1 times / day
Sources: Page: p. 300
unhealthy, adult
n = 2736
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 2736
Sources: Page: p. 300
AST increased 0.4%
Disc. AE
25 mg 1 times / day steady, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: steady
Dose: 25 mg, 1 times / day
Sources: Page: p. 300
unhealthy, adult
n = 2736
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 2736
Sources: Page: p. 300
Bilirubin increased 0.4%
Disc. AE
25 mg 1 times / day steady, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: steady
Dose: 25 mg, 1 times / day
Sources: Page: p. 300
unhealthy, adult
n = 2736
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 2736
Sources: Page: p. 300
Liver enzyme abnormal 0.4%
Disc. AE
25 mg 1 times / day steady, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: steady
Dose: 25 mg, 1 times / day
Sources: Page: p. 300
unhealthy, adult
n = 2736
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 2736
Sources: Page: p. 300
Atrial fibrillation 0.5%
Disc. AE
25 mg 1 times / day steady, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: steady
Dose: 25 mg, 1 times / day
Sources: Page: p. 300
unhealthy, adult
n = 2736
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 2736
Sources: Page: p. 300
Edema peripheral 0.5%
Disc. AE
25 mg 1 times / day steady, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: steady
Dose: 25 mg, 1 times / day
Sources: Page: p. 300
unhealthy, adult
n = 2736
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 2736
Sources: Page: p. 300
Palpitations 0.5%
Disc. AE
25 mg 1 times / day steady, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: steady
Dose: 25 mg, 1 times / day
Sources: Page: p. 300
unhealthy, adult
n = 2736
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 2736
Sources: Page: p. 300
Pyrexia 0.5%
Disc. AE
25 mg 1 times / day steady, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: steady
Dose: 25 mg, 1 times / day
Sources: Page: p. 300
unhealthy, adult
n = 2736
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 2736
Sources: Page: p. 300
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
moderate
yes (co-administration study)
Comment: Cmax and AUC of metoprolol increased by 90% and 229% and of desipramine by 79% and 241%, respectively; The Cmax and AUC of tamsulosin was increased by 60% when co-administered with mirabegron
Page: 27.0
no
no
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
weak
weak
weak
weak
yes (co-administration study)
Comment: The Cmax and AUC of tamsulosin (a CYP2D6 and CYP3A4 substrate) was increased by 60% when co-administered with mirabegron
Page: 30.0
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
yes (co-administration study)
Comment: Ketoconazole (inhibitor) increased the Cmax and AUC of mirabegron by 45% and 81%; rifampin (inducer) reduced the Cmax and AUC by 35% and 44%, respectively;
Page: 27.0
minor
minor
minor
no
no
yes
yes
yes
yes
yes
yes (co-administration study)
Comment: Ketoconazole (inhibitor) increased the Cmax and AUC of mirabegron by 45% and 81%; rifampin (inducer) reduced the Cmax and AUC by 35% and 44%, respectively;
Page: 27.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Beta3-adrenoceptors in human detrusor muscle.
2002 May
Relaxation of human detrusor muscle by selective beta-2 and beta-3 agonists and endogenous catecholamines.
2007 Apr
Effect of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl} acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function.
2007 May
Gateways to clinical trials.
2008 Jun
Effect of pre-contraction on β-adrenoceptor-mediated relaxation of rat urinary bladder.
2009 Dec
Pharmacotherapy of the overactive bladder.
2009 Oct
Tissue functions mediated by beta(3)-adrenoceptors-findings and challenges.
2010 Aug
Beta3-adrenoceptor agonists: possible role in the treatment of overactive bladder.
2010 Dec
Mirabegron, a β₃-adrenoceptor agonist for the potential treatment of urinary frequency, urinary incontinence or urgency associated with overactive bladder.
2010 Oct
The pharmacokinetic evaluation of mirabegron as an overactive bladder therapy option.
2013 May
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.
2015 May 18
Patents

Sample Use Guides

25 mg once daily, with or without food. 25 mg is effective within 8 weeks. Based on individual efficacy and tolerability, may increase dose to 50 mg once daily.
Route of Administration: Oral
In Vitro Use Guide
Mirabegron increased cAMP accumulation with EC(50) value = 19 nmol/L in CHO cells expressing rat β(3)-adrenoceptors.
Substance Class Chemical
Created
by admin
on Sat Jun 26 06:07:21 UTC 2021
Edited
by admin
on Sat Jun 26 06:07:21 UTC 2021
Record UNII
MVR3JL3B2V
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MIRABEGRON
DASH   INN   JAN   MART.   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
MIRABEGRON [USAN]
Common Name English
YM178
Code English
MIRABEGRON [INN]
Common Name English
4-THIAZOLEACETAMIDE, 2-AMINO-N-(4-(2-(((2R)-2-HYDROXY-2-PHENYLETHYL)AMINO)ETHYL)PHENYL)-
Systematic Name English
BETMIGA
Brand Name English
2-(2-AMINOTHIAZOL-4-YL)-N-(4-(2-(((2R)-2-HYDROXY-2-PHENYLETHYL)AMINO)ETHYL)PHENYL)ACETAMIDE
Systematic Name English
YM-178
Code English
MYRBETRIQ
Brand Name English
MIRABEGRON [ORANGE BOOK]
Common Name English
BETANIS
Brand Name English
MIRABEGRON [WHO-DD]
Common Name English
MIRABEGRON [MART.]
Common Name English
MIRABEGRON [VANDF]
Common Name English
MIRABEGRON [MI]
Common Name English
MIRABEGRON [JAN]
Common Name English
2-(2-AMINO-1,3-THIAZOL-4-YL)-N-(4-(2-(((2R)-2-HYDROXY-2-PHENYLETHYL)AMINO)ETHYL)PHENYL)ACETAMIDE
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C48149
Created by admin on Sat Jun 26 06:07:21 UTC 2021 , Edited by admin on Sat Jun 26 06:07:21 UTC 2021
LIVERTOX 642
Created by admin on Sat Jun 26 06:07:21 UTC 2021 , Edited by admin on Sat Jun 26 06:07:21 UTC 2021
NDF-RT N0000185008
Created by admin on Sat Jun 26 06:07:21 UTC 2021 , Edited by admin on Sat Jun 26 06:07:21 UTC 2021
WHO-VATC QG04BD12
Created by admin on Sat Jun 26 06:07:21 UTC 2021 , Edited by admin on Sat Jun 26 06:07:21 UTC 2021
WHO-ATC G04BD12
Created by admin on Sat Jun 26 06:07:21 UTC 2021 , Edited by admin on Sat Jun 26 06:07:21 UTC 2021
EMA ASSESSMENT REPORTS BETMIGA (AUTHORIZED: URINARY BLADDER, OVERACTIVE)
Created by admin on Sat Jun 26 06:07:21 UTC 2021 , Edited by admin on Sat Jun 26 06:07:21 UTC 2021
Code System Code Type Description
DRUG BANK
DB08893
Created by admin on Sat Jun 26 06:07:21 UTC 2021 , Edited by admin on Sat Jun 26 06:07:21 UTC 2021
PRIMARY
INN
8907
Created by admin on Sat Jun 26 06:07:21 UTC 2021 , Edited by admin on Sat Jun 26 06:07:21 UTC 2021
PRIMARY
PUBCHEM
9865528
Created by admin on Sat Jun 26 06:07:21 UTC 2021 , Edited by admin on Sat Jun 26 06:07:21 UTC 2021
PRIMARY
LACTMED
Mirabegron
Created by admin on Sat Jun 26 06:07:21 UTC 2021 , Edited by admin on Sat Jun 26 06:07:21 UTC 2021
PRIMARY
WIKIPEDIA
Mirabegron
Created by admin on Sat Jun 26 06:07:21 UTC 2021 , Edited by admin on Sat Jun 26 06:07:21 UTC 2021
PRIMARY
ChEMBL
CHEMBL2095212
Created by admin on Sat Jun 26 06:07:21 UTC 2021 , Edited by admin on Sat Jun 26 06:07:21 UTC 2021
PRIMARY
NDF-RT
N0000185007
Created by admin on Sat Jun 26 06:07:21 UTC 2021 , Edited by admin on Sat Jun 26 06:07:21 UTC 2021
PRIMARY Adrenergic beta3-Agonists [MoA]
MERCK INDEX
M11690
Created by admin on Sat Jun 26 06:07:21 UTC 2021 , Edited by admin on Sat Jun 26 06:07:21 UTC 2021
PRIMARY
FDA UNII
MVR3JL3B2V
Created by admin on Sat Jun 26 06:07:21 UTC 2021 , Edited by admin on Sat Jun 26 06:07:21 UTC 2021
PRIMARY
JAPANESE REVIEW
BETANIS
Created by admin on Sat Jun 26 06:07:21 UTC 2021 , Edited by admin on Sat Jun 26 06:07:21 UTC 2021
PRIMARY APPROVED JUNE 2011
CAS
223673-61-8
Created by admin on Sat Jun 26 06:07:21 UTC 2021 , Edited by admin on Sat Jun 26 06:07:21 UTC 2021
PRIMARY
IUPHAR
7445
Created by admin on Sat Jun 26 06:07:21 UTC 2021 , Edited by admin on Sat Jun 26 06:07:21 UTC 2021
PRIMARY
NDF-RT
N0000182137
Created by admin on Sat Jun 26 06:07:21 UTC 2021 , Edited by admin on Sat Jun 26 06:07:21 UTC 2021
PRIMARY Cytochrome P450 2D6 Inhibitors [MoA]
EVMPD
SUB32690
Created by admin on Sat Jun 26 06:07:21 UTC 2021 , Edited by admin on Sat Jun 26 06:07:21 UTC 2021
PRIMARY
NCI_THESAURUS
C90633
Created by admin on Sat Jun 26 06:07:21 UTC 2021 , Edited by admin on Sat Jun 26 06:07:21 UTC 2021
PRIMARY
RXCUI
1300786
Created by admin on Sat Jun 26 06:07:21 UTC 2021 , Edited by admin on Sat Jun 26 06:07:21 UTC 2021
PRIMARY RxNorm
DRUG CENTRAL
4382
Created by admin on Sat Jun 26 06:07:21 UTC 2021 , Edited by admin on Sat Jun 26 06:07:21 UTC 2021
PRIMARY
Related Record Type Details
TARGET -> AGONIST
SHORT-ACTING
Related Record Type Details
METABOLITE -> PARENT
CYP 3A4 is the primary responsible isoenzyme for in vitro hepatic oxidative metabolism of mirabegron, with a minor role of CYP2D6
METABOLITE -> PARENT
PLASMA; URINE
METABOLITE -> PARENT
PLASMA; URINE
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
In vitro studies suggest a role for CYP2D6 and CYP3A4 in the oxidative metabolism of mirabegron
METABOLITE -> PARENT
PLASMA; URINE
METABOLITE INACTIVE -> PARENT
METABOLITE -> PARENT
PLASMA; URINE
METABOLITE INACTIVE -> PARENT
In vitro and ex vivo studies have shown the involvement of uridine diphospho-glucuronosyltransferases (UGT)
METABOLITE -> PARENT
PLASMA
METABOLITE -> PARENT
URINE
METABOLITE INACTIVE -> PARENT
MAJOR
PLASMA; URINE
METABOLITE INACTIVE -> PARENT
MAJOR
PLASMA; URINE
METABOLITE -> PARENT
PLASMA; URINE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC Elimination
PHARMACOKINETIC