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Details

Stereochemistry ABSOLUTE
Molecular Formula C19H23NO3
Molecular Weight 313.3915
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MAVOGLURANT

SMILES

Cc1cccc(C#C[C@@]2(CCC[C@]3([H])[C@@]2([H])CCN3C(=O)OC)O)c1

InChI

InChIKey=ZFPZEYHRWGMJCV-ZHALLVOQSA-N
InChI=1S/C19H23NO3/c1-14-5-3-6-15(13-14)8-11-19(22)10-4-7-17-16(19)9-12-20(17)18(21)23-2/h3,5-6,13,16-17,22H,4,7,9-10,12H2,1-2H3/t16-,17-,19-/m1/s1

HIDE SMILES / InChI

Molecular Formula C19H23NO3
Molecular Weight 313.3915
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

Mavoglurant (AFQ056) was developed as a new metabotropic glutamate receptor 5 (mGluR5) antagonist. The efficacy of mavoglurant in humans has been assessed in L-dopa induced dyskinesia in Parkinson's disease and Fragile X syndrome in proof of principle clinical studies. However, Novartis had announced that the company would be discontinuing its development program in Fragile X following negative results in a large international clinical trial in adults, and more recently in a trial in adolescents. In both placebo-controlled trials, patients taking mavoglurant did not show improvement over placebo in any outcome measures. In patients with L-Dopa-induced dyskinesias studies failed to meet the primary objective of demonstrating improvement of dyskinesia. Mavoglurant was also investigated in phase II clinical trials to reduce chorea in Huntington's disease, but the target result was not achieved. Currently Novartis is conducting a phase II clinical trial to demonstrate whether or not this drug can benificially reduce cocaine use in Cocaine Use Disorder.

CNS Activity

Curator's Comment:: Known to be CNS penetrant in mouse. Human data not available

Originator

Curator's Comment:: # Novartis Institutes for BioMedical Researc

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P41594
Gene ID: 2915.0
Gene Symbol: GRM5
Target Organism: Homo sapiens (Human)
30.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
447 nM
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MAVOGLURANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
832 ng/mL
50 mg single, intravenous
dose: 50 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MAVOGLURANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
6292 nM × h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MAVOGLURANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
1760 ng × h/mL
50 mg single, intravenous
dose: 50 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MAVOGLURANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
12 h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MAVOGLURANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
9.11 h
50 mg single, intravenous
dose: 50 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MAVOGLURANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
400 mg single, oral
Highest studied dose
Dose: 400 mg
Route: oral
Route: single
Dose: 400 mg
Sources:
unhealthy, ADULT
n = 11
Health Status: unhealthy
Condition: gastroesophageal reflux disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 11
Sources:
50 mg single, intravenous
Highest studied dose
Dose: 50 mg
Route: intravenous
Route: single
Dose: 50 mg
Sources: Page: p.2593
healthy, ADULT
n = 12
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 12
Sources: Page: p.2593
Disc. AE: Sinoatrial block...
AEs leading to
discontinuation/dose reduction:
Sinoatrial block (8.3%)
Sources: Page: p.2593
150 mg 2 times / day multiple, oral (max)
Studied dose
Dose: 150 mg, 2 times / day
Route: oral
Route: multiple
Dose: 150 mg, 2 times / day
Sources: Page: p.3
unhealthy, ADULT
n = 21
Health Status: unhealthy
Condition: Huntington's disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 21
Sources: Page: p.3
Disc. AE: Disorientation...
AEs leading to
discontinuation/dose reduction:
Disorientation (4.8%)
Sources: Page: p.3
AEs

AEs

AESignificanceDosePopulation
Sinoatrial block 8.3%
Disc. AE
50 mg single, intravenous
Highest studied dose
Dose: 50 mg
Route: intravenous
Route: single
Dose: 50 mg
Sources: Page: p.2593
healthy, ADULT
n = 12
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 12
Sources: Page: p.2593
Disorientation 4.8%
Disc. AE
150 mg 2 times / day multiple, oral (max)
Studied dose
Dose: 150 mg, 2 times / day
Route: oral
Route: multiple
Dose: 150 mg, 2 times / day
Sources: Page: p.3
unhealthy, ADULT
n = 21
Health Status: unhealthy
Condition: Huntington's disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 21
Sources: Page: p.3
PubMed

PubMed

TitleDatePubMed
AFQ056/mavoglurant, a novel clinically effective mGluR5 antagonist: identification, SAR and pharmacological characterization.
2014 Nov 1
Patents

Patents

Sample Use Guides

l-Dopa-induced dyskinesias: mavoglurant (AFQ056) was up-titrated over two weeks from 25 mg twice daily (bid) to 100 mg bid (L-dopa kept stable), followed by three weeks during which the daily L-dopa dosage was increased by up to 300 mg/day. The study was a randomized, placebo- and active-controlled, 4-period, crossover, conduct of thorough QTc (TQT) study composed of 2 sequential phases. In the pilot phase, the safety and tolerability profile of 10-minute infusions of 25, 37.5, and 50 mg of mavoglurant was assessed in 36 healthy individuals. In the TQT phase, individuals received in random sequence single intravenous doses of mavoglurant (25 and 50 mg) and placebo and an oral dose of moxifloxacin (400 mg).
Route of Administration: Other
AFQ056/mavoglurant was identified by chemical derivatization of a lead compound discovered in a HTS campaign. In vitro, AFQ056/mavoglurant had an IC50 of 30 nM in a functional assay with human mGluR5 and was selective over the other mGluR subtypes, iGluRs and a panel of 238 CNS relevant receptors, transporter or enzymes.
Substance Class Chemical
Created
by admin
on Fri Jun 25 22:53:24 UTC 2021
Edited
by admin
on Fri Jun 25 22:53:24 UTC 2021
Record UNII
GT0I9SV4F6
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MAVOGLURANT
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
1H-INDOLE-1-CARBOXYLIC ACID, OCTAHYDRO-4-HYDROXY-4-((3-METHYLPHENYL)ETHYNYL)-, METHYL ESTER, (3AR,4S,7AR)-
Common Name English
METHYL (3AR,4S,7AR)-4-HYDROXY-4-(2-(3-METHYLPHENYL)ETHYNYL)OCTAHYDRO-1H-INDOLE-1-CARBOXYLATE
Common Name English
(-)-(3AR,4S,7AR)-4-HYDROXY-4-M-TOLYLETHYNYL-OCTAHYDRO-INDOLE-1-CARBOXYLIC ACID METHYL ESTER
Systematic Name English
AFQ-056
Code English
MAVOGLURANT [WHO-DD]
Common Name English
1H-INDOLE-1-CARBOXYLIC ACID, OCTAHYDRO-4-HYDROXY-4-(2-(3-METHYLPHENYL)ETHYNYL)-, METHYL ESTER, (3AR,4S,7AR)-
Common Name English
MAVOGLURANT [USAN]
Common Name English
MAVOGLURANT [INN]
Common Name English
AFQ056
Code English
Classification Tree Code System Code
FDA ORPHAN DRUG 353611
Created by admin on Fri Jun 25 22:53:24 UTC 2021 , Edited by admin on Fri Jun 25 22:53:24 UTC 2021
EU-Orphan Drug EU/3/12/1046
Created by admin on Fri Jun 25 22:53:24 UTC 2021 , Edited by admin on Fri Jun 25 22:53:24 UTC 2021
Code System Code Type Description
INN
9395
Created by admin on Fri Jun 25 22:53:24 UTC 2021 , Edited by admin on Fri Jun 25 22:53:24 UTC 2021
PRIMARY
ChEMBL
CHEMBL3087515
Created by admin on Fri Jun 25 22:53:24 UTC 2021 , Edited by admin on Fri Jun 25 22:53:24 UTC 2021
PRIMARY
PUBCHEM
9926832
Created by admin on Fri Jun 25 22:53:24 UTC 2021 , Edited by admin on Fri Jun 25 22:53:24 UTC 2021
PRIMARY
FDA UNII
GT0I9SV4F6
Created by admin on Fri Jun 25 22:53:24 UTC 2021 , Edited by admin on Fri Jun 25 22:53:24 UTC 2021
PRIMARY
CAS
543906-09-8
Created by admin on Fri Jun 25 22:53:24 UTC 2021 , Edited by admin on Fri Jun 25 22:53:24 UTC 2021
PRIMARY
DRUG BANK
DB13004
Created by admin on Fri Jun 25 22:53:24 UTC 2021 , Edited by admin on Fri Jun 25 22:53:24 UTC 2021
PRIMARY
NCI_THESAURUS
C170154
Created by admin on Fri Jun 25 22:53:24 UTC 2021 , Edited by admin on Fri Jun 25 22:53:24 UTC 2021
PRIMARY
EPA CompTox
543906-09-8
Created by admin on Fri Jun 25 22:53:24 UTC 2021 , Edited by admin on Fri Jun 25 22:53:24 UTC 2021
PRIMARY
WIKIPEDIA
MAVOGLURANT
Created by admin on Fri Jun 25 22:53:24 UTC 2021 , Edited by admin on Fri Jun 25 22:53:24 UTC 2021
PRIMARY
Related Record Type Details
TARGET->ANTAGONIST
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
AMOUNT EXCRETED
FECAL
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
No parent compound was detected in urine
URINE
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METABOLITE -> PARENT
PLASMA; URINE
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
PLASMA
METABOLITE -> PARENT
PLASMA
METABOLITE -> PARENT
PLASMA
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
PLASMA
METABOLITE -> PARENT
PLASMA
METABOLITE -> PARENT
PLASMA
METABOLITE -> PARENT
FECAL
METABOLITE -> PARENT
PLASMA
METABOLITE -> PARENT
PLASMA
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

SINGLE DOSE

Biological Half-life PHARMACOKINETIC SINGLE DOSE

ORAL ADMINISTRATION