VIXOTRIGINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H19FN2O2
Molecular Weight	314.3541
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC(=O)[C@@H]1CC[C@@H](N1)C2=CC=C(OCC3=CC=CC=C3F)C=C2

InChI

InChIKey=JESCETIFNOFKEU-SJORKVTESA-N

InChI=1S/C18H19FN2O2/c19-15-4-2-1-3-13(15)11-23-14-7-5-12(6-8-14)16-9-10-17(21-16)18(20)22/h1-8,16-17,21H,9-11H2,(H2,20,22)/t16-,17+/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=RAXATRIGINE

Raxatrigine also known as GSK1014802 and CNV-1014802, is a novel analgesic under development by Convergence Pharmaceuticals for the treatment of lumbosacral radiculopathy (sciatica) and trigeminal neuralgia (TGN). It is a novel state dependent small molecule sodium channel blocker that preferentially inhibits the Nav 1.7 ion channel, a therapeutic target implicated by genetics in human pain conditions. Raxatrigine is thought to penetrate the central nervous system and block Nav channels in a novel manner. CNV1014802 was granted orphan drug designation in 2013 by the US Food and Drug Administration (FDA) for the treatment of trigeminal neuralgia.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Sodium channel protein type IX alpha subunit 21 Target ID: CHEMBL4296 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26646477	Blocker 537

Conditions

Condition	Modality	Highest Phase	Product
Trigeminal neuralgia 9 Sources: https://clinicaltrials.gov/ct2/show/NCT01540630	Palliative	Phase II 1132	Unknown Approved Use Unknown
Lumbosacral radiculopathy 5 Sources: https://clinicaltrials.gov/ct2/show/NCT01561027	Palliative	Phase II 1132	Unknown Approved Use Unknown
Bipolar disorder 34 Sources: https://clinicaltrials.gov/ct2/show/NCT00908154	Palliative	Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
4410 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30144099	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		RAXATRIGINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3780 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30144099	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		RAXATRIGINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
60100 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30144099	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		RAXATRIGINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
38700 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30144099	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		RAXATRIGINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.91 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30144099	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		RAXATRIGINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 substrate 1737	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C8 911 CYP2A6 707 CYP2C19 1478 P-gp 1461 OATP1B1 788 OATP1B3 706 BCRP 699 OAT1 599 Nav1.5 97 CYP2B6 810 OCT2 647	CYPs 33 UGTs 13 UGT2B7 389 UGT1A3 422

Drug as perpetrator

Target	Modality	Activity
CYP2A6 739	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32945812/	no [IC50 >100 uM]
CYP2C8 965	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32945812/	no [IC50 >100 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32945812/	no [IC50 >100 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32945812/	no [IC50 >100 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32945812/	no [IC50 >100 uM]
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32945812/	no [Inhibition 100 uM]
BCRP 773	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32945812/	no
OAT1 603	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32945812/	no
OATP1B1 803	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32945812/	no
OATP1B3 715	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32945812/	no
OCT2 648	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32945812/	no
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32945812/	weak [IC50 79 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32945812/	yes [IC50 13 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32945812/	yes [IC50 31 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
UGTs 13	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/32564301/ \| https://pubmed.ncbi.nlm.nih.gov/31650711/	major	yes (co-administration study) Comment: Carbamazepine decreased AUCtau and Cmax by 31.6% and 26.3%. Sources: https://pubmed.ncbi.nlm.nih.gov/32564301/ \| https://pubmed.ncbi.nlm.nih.gov/31650711/
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/31650711/	minor
CYPs 33	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/32564301/	minor	(co-administration study) Sources: https://pubmed.ncbi.nlm.nih.gov/32564301/
UGT1A3 422	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/31650711/	yes
UGT2B7 389	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/31650711/	yes	yes (co-administration study) Comment: Carbamazepine decreased AUCtau and Cmax by 31.6% and 26.3%. Sources: https://pubmed.ncbi.nlm.nih.gov/31650711/

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
Nav1.5 100	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/33298520/
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/32945812/

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P0039QY	https://www.1pchem.com/search?query=1P0039QY
1PlusChem LLC	1P00GUOW	https://www.1pchem.com/search?query=1P00GUOW
1PlusChem LLC	1P01DK95	https://www.1pchem.com/search?query=1P01DK95
A2B Chem	AX11593	http://a2bchem.com/prod/AX11593
AChemBlock	H-8916	http://www.achemblock.com/catalogsearch/result/?q=H-8916
Ambeed	A139957	http://www.ambeed.com/search/Search.html?keyword=A139957
Angene	AGN-PC-0WH9ZT	http://www.angenechemical.com/productshow/AGN-PC-0WH9ZT.html
ApexBio Technology	B5927	https://www.apexbt.com/catalogsearch/result/?q=B5927
AstaTech	I10406	http://astatechinc.com/CPSResult.php?CRNO=I10406
AstaTech	W11967	http://astatechinc.com/CPSResult.php?CRNO=W11967
Axon MedChem	1899	https://www.axonmedchem.com/product/1899
Axon MedChem	2548	https://www.axonmedchem.com/product/2548
BLD Pharm	BD292205	http://www.bldpharm.com/search/Search.html?keyword=BD292205
BLD Pharm	BD302241	http://www.bldpharm.com/search/Search.html?keyword=BD302241
Chem Scene	CS-0047524	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0047524
Chem Scene	CS-4038	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-4038
Chem Scene	CS-4039	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-4039
ChemShuttle	134202	https://www.chemshuttle.com/catalogsearch/result/?q=134202
Combi-Blocks	QV-3166	http://www.combi-blocks.com/cgi-bin/find.cgi?QV-3166
Fluorochem	501198	http://www.fluorochem.co.uk/Products/Product?code=501198
Hairui	RACQ030	http://www.hairuichem.com/en/product/search.do?q=RACQ030
KeyOrganics	AS-49442	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-49442
KeyOrganics	AS-56210	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-56210
KeyOrganics	AS-71639	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-71639
Lab Network	LN01342413	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01342413
Lab Network	LN01342414	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01342414
Lab Network	LN02184702	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN02184702
Matrix Scientific	153879	http://www.matrixscientific.com/153879.html
MedChem Express	HY-12796	https://www.medchemexpress.com/search.html?q=HY-12796A&ft=&fa=&fp=
MedChem Express	HY-12796A	https://www.medchemexpress.com/search.html?q=HY-12796A&ft=&fa=&fp=
MolPort	MolPort-028-720-421	https://www.molport.com/shop/molecule-link/MolPort-028-720-421
MolPort	MolPort-039-137-020	https://www.molport.com/shop/molecule-link/MolPort-039-137-020
MolPort	MolPort-046-591-460	https://www.molport.com/shop/molecule-link/MolPort-046-591-460
Molnova	M16676	https://www.molnova.com/en/serch-list.html?keywords=M16676
Molnova	M16677	https://www.molnova.com/en/serch-list.html?keywords=M16677
MuseChem	I008980	https://www.musechem.com/product/I008980.html
MuseChem	I008981	https://www.musechem.com/product/I008981.html
Ryan Scientific	PF_431396	https://ryansci.com/products?q=PF_431396&list_q=&search_type=exact
ShangHai Biochempartner	BCP000767	http://www.biochempartner.com/search_BCP000767
TargetMol	T2342	https://www.targetmol.com/search?keyword=T2342
Toronto Research Chemicals	R128055	https://www.trc-canada.com/product-detail/?CatNum=R128055
eMolecules	195315690	https://orderbb.emolecules.com/search/#?query=195315690
eMolecules	266610487	https://orderbb.emolecules.com/search/#?query=266610487
eMolecules	44818030	https://orderbb.emolecules.com/search/#?query=44818030
eMolecules	53744810	https://orderbb.emolecules.com/search/#?query=53744810
eMolecules	95575190	https://orderbb.emolecules.com/search/#?query=95575190
eNovation Chemicals	D501824	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D501824&searchbtn.x=0&searchbtn.y=0
eNovation Chemicals	D521798	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D521798&searchbtn.x=0&searchbtn.y=0
eNovation Chemicals	D774572	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D774572&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-1569438066	https://mcule.com/MCULE-1569438066/
mcule	MCULE-3210241523	https://mcule.com/MCULE-3210241523/
mcule	MCULE-7010850478	https://mcule.com/MCULE-7010850478/

PubMed

Title	Date	PubMed
		252160552

Patents

Sample Use Guides

In Vivo Use Guide

Trigeminal Neuralgia: 21 days of 50mg three times a day Lumbosacral Radiculopathy: 350mg twice (two times) a day for 21 days

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

VIXOTRIGINE

Official Name

English

VIXOTRIGINE [USAN]

Common Name

English

Vixotrigine [WHO-DD]

Common Name

English

vixotrigine [INN]

Common Name

English

(2S,5R)-5-(4-((2-FLUOROPHENYL)METHOXY)PHENYL)PYRROLIDINE-2-CARBOXAMIDE

Systematic Name

English

CNV-1014802

Code

English

BIIB-074

Code

English

CNV1014802

Code

English

GSK-1014802

Code

English

RAXATRIGINE

Official Name

English

2-PYRROLIDINECARBOXAMIDE, 5-(4-((2-FLUOROPHENYL)METHOXY)PHENYL)-, (2S,5R)-

Systematic Name

English

GSK1014802

Code

English

BIIB074

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C241