BASIMGLURANT SULFATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C18H13ClFN3.H2O4S
Molecular Weight	423.846
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OS(O)(=O)=O.CC1=NC(C#CC2=CC(Cl)=NC=C2)=C(C)N1C3=CC=C(F)C=C3

InChI

InChIKey=RPRPXJNEEIIWAL-UHFFFAOYSA-N

InChI=1S/C18H13ClFN3.H2O4S/c1-12-17(8-3-14-9-10-21-18(19)11-14)22-13(2)23(12)16-6-4-15(20)5-7-16;1-5(2,3)4/h4-7,9-11H,1-2H3;(H2,1,2,3,4)

HIDE SMILES / InChI

Molecular Formula	C18H13ClFN3
Molecular Weight	325.767
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	H2O4S
Molecular Weight	98.078
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25665805
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800024877 https://www.ncbi.nlm.nih.gov/pubmed/26219727

Basimglurant is a potent, selective, and safe mGlu5 inhibitor with good oral bioavailability and long half-life supportive of once-daily administration, good brain penetration, and high in vivo potency. It has antidepressant properties that are corroborated by its functional magnetic imaging profile as well as anxiolytic-like and antinociceptive features. In electroencephalography recordings, basimglurant shows wake-promoting effects followed by increased delta power during subsequent non-rapid eye movement sleep. Basimglurant has favorable drug-like properties, a differentiated molecular mechanism of action, and antidepressant-like features that suggest the possibility of also addressing important comorbidities of MDD including anxiety and pain as well as daytime sleepiness and apathy or lethargy. Basimglurant is being under development by Roche for the treatment of treatment-resistant depression (as an adjunct). It is in phase II clinical trials for this indication.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Metabotropic glutamate receptor 5 39 Target ID: CHEMBL3227 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25565255 https://www.ncbi.nlm.nih.gov/pubmed/25665805	Negative Allosteric Modulator 42		7.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Major depressive disorder 173 Sources: https://clinicaltrials.gov/ct2/show/NCT01437657	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
16.3 ng × eq/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27123695	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:		BASIMGLURANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
296 ng × eq × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27123695	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:		BASIMGLURANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
178 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27123695	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:		BASIMGLURANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	substrate 1037	substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2B6 664 CYP2E1 667 CYP2C8 693 UGT1A1 418 CYP4A11 119 UGT1A6 307 UGT1A4 347 CYP1A2 1054 CYP3A4/5 85 CYP2C19 991 UGT1A9 380 UGT2B7 389 UGT1A3 422 CYP1A1 349 UGT1A7 236 CYP2A6 543 UGT1A8 283 UGT2B10 127 UGT1A10 291 P-gp 1537 UGT2B4 249 UGT2B15 203 UGT2B17 213

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
UGT2B17 213	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	likely	M1 13
UGT2B17 213	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	likely	M2 9
UGT2B7 389	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	likely	M2 9
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	major [Km 6.8 uM]		yes (co-administration study) Comment: Fluvoxamine increased AUC by 60%. Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/
UGT1A9 380	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	major	M1 13
UGT1A9 380	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	major	M2 9
UGT1A10 291	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	minor	M2 9
UGT1A7 236	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	minor	M2 9
CYP3A4/5 85	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	minor		yes (co-administration study) Comment: Ketoconazole increased Cmax and AUC by 3% and 24%. Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/
CYP2A6 543	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	no
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	no
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	no
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	no
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	no
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	no
CYP4A11 119	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	no
P-gp 1537	substrate 3367 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363680975	no
UGT1A1 418	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	no	M1 13
UGT1A1 418	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	no	M2 9
UGT1A10 291	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	no	M1 13
UGT1A3 422	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	no	M2 9
UGT1A4 347	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	no	M1 13
UGT1A4 347	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	no	M2 9
UGT1A6 307	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	no	M1 13
UGT1A6 307	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	no	M2 9
UGT1A8 283	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	no	M1 13
UGT1A8 283	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	no	M2 9
UGT2B10 127	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	no	M1 13
UGT2B10 127	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	no	M2 9
UGT2B15 203	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	no	M1 13
UGT2B15 203	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	no	M2 9
UGT2B4 249	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	no	M1 13
UGT2B4 249	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	no	M2 9
CYP1A1 349	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	yes [Km 4.2 uM]
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	yes [Km 48 uM]
UGT1A3 422	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	yes	M1 13
UGT1A7 236	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	yes	M1 13
UGT2B7 389	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27821711/	yes	M1 13

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/25565255/

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00G44Q	https://www.1pchem.com/search?query=1P00G44Q
A2B Chem	AH51050	http://a2bchem.com/prod/AH51050
AChemBlock	L13487	http://www.achemblock.com/catalogsearch/result/?q=L13487
ApexBio Technology	B4808	https://www.apexbt.com/catalogsearch/result/?q=B4808
AstaTech	P14045	http://astatechinc.com/CPSResult.php?CRNO=P14045
BLD Pharm	BD301060	http://www.bldpharm.com/search/Search.html?keyword=BD301060
Chem Scene	CS-3388	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3388
Combi-Blocks	QM-8773	http://www.combi-blocks.com/cgi-bin/find.cgi?QM-8773
KeyOrganics	AS-51978	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-51978
Lab Network	LN01341873	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01341873
MedChem Express	HY-15446	https://www.medchemexpress.com/search.html?q=HY-15446&ft=&fa=&fp=
MolPort	MolPort-039-063-482	https://www.molport.com/shop/molecule-link/MolPort-039-063-482
MuseChem	I003950	https://www.musechem.com/product/I003950.html
ShangHai Biochempartner	BCP15864	http://www.biochempartner.com/search_BCP15864
eMolecules	50281307	https://orderbb.emolecules.com/search/#?query=50281307
mcule	MCULE-4074341289	https://mcule.com/MCULE-4074341289/

PubMed

Title	Date	PubMed
Pharmacology of basimglurant (RO4917523, RG7090), a unique metabotropic glutamate receptor 5 negative allosteric modulator in clinical development for depression.	2015 Apr	25665805

Patents

Sample Use Guides

In Vivo Use Guide

Participants will receive once-daily oral basimglurant capsules in a multiple ascending dose regimen. Basimglurant dose will be titrated over 22 days; dose escalations will be separated by at least 4 days, with the final dose administered for a minimum of 14 days. The minimum starting dose will be 1.5 mg, which can be titrated up to a maximum dose of 4.0 mg. Intrapatient dose increments will not exceed 1.0 mg every 4 days.

Route of Administration: Oral

In Vitro Use Guide

Basimglurant bound with a nanomolar affinity (Ki 36nM) to the allosteric binding sites of the 3H-MPEP, the classical mGlu5 NAM, in the TM domains. In HEK293 cells stably expressing human mGlu5, basimglurant inhibited quisqualate-induced Ca2+ mobilization, with an IC50 7.0 nM, and [3H]inositol phosphate accumulation, with an IC50 5.9 nM

Substance Class	Chemical Created by `admin` on `Fri Dec 15 17:33:45 GMT 2023` Edited by `admin` on `Fri Dec 15 17:33:45 GMT 2023`
Record UNII	MQ04IL403Q
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BASIMGLURANT SULFATE

Common Name

English

RO-4917523 SULPHATE

Common Name

English

NOE-101 SULFATE

Code

English

PYRIDINE, 2-CHLORO-4-(2-(1-(4-FLUOROPHENYL)-2,5-DIMETHYL-1H-IMIDAZOL-4-YL)ETHYNYL)-, SULFATE (1:1)

Systematic Name

English

RO4917523 SULPHATE

Common Name

English

Code System Code Type Description

PUBCHEM

131634700

Created by admin on Fri Dec 15 17:33:45 GMT 2023 , Edited by admin on Fri Dec 15 17:33:45 GMT 2023

PRIMARY

FDA UNII

MQ04IL403Q

Created by admin on Fri Dec 15 17:33:45 GMT 2023 , Edited by admin on Fri Dec 15 17:33:45 GMT 2023

PRIMARY

CAS

1034442-21-1

Created by admin on Fri Dec 15 17:33:45 GMT 2023 , Edited by admin on Fri Dec 15 17:33:45 GMT 2023

PRIMARY

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BASIMGLURANT

PARENT -> SALT/SOLVATE

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					3110E3AO8S

BASIMGLURANT

ACTIVE MOIETY

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/25665805Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800024877 https://www.ncbi.nlm.nih.gov/pubmed/26219727

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Cmax

AUC

T1/2

Overview

OverviewOther

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25665805
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800024877 https://www.ncbi.nlm.nih.gov/pubmed/26219727

C_max

T_1/2