INTEPIRDINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H19N3O2S
Molecular Weight	353.438
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O=S(=O)(C1=CC=CC=C1)C2=CC3=CC=CC(N4CCNCC4)=C3N=C2

InChI

InChIKey=JJZFWROHYSMCMU-UHFFFAOYSA-N

InChI=1S/C19H19N3O2S/c23-25(24,16-6-2-1-3-7-16)17-13-15-5-4-8-18(19(15)21-14-17)22-11-9-20-10-12-22/h1-8,13-14,20H,9-12H2

HIDE SMILES / InChI

Molecular Formula	C19H19N3O2S
Molecular Weight	353.438
Charge	0
Count

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

Description
Sources: http://www.alzforum.org/therapeutics/intepirdine
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/20043816

Intepirdine, also known as SB-742457, RVT-101, was originally developed by GlaxoSmithKline (GSK) as an antagonist of the serotonin receptor 6 (5-HT6). GSK sold the rights for further study of this drug to Axovant Sciences in 2014. Intepirdine is in phase 3 clinical trial for Alzheimer's and in a phase 2 trial for dementia with Lewy bodies.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serotonin 6 (5-HT6) receptor 45 Target ID: CHEMBL3371 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27914038	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Alzheimer’s disease 272 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20872778	Primary		Phase III 656	Unknown Approved Use Unknown
Dementia with lewy bodies 1 Sources: https://clinicaltrials.gov/ct2/show/NCT02669433	Primary		Phase II 1132	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
50 mg 1 times / day steady-state, oral Highest studied dose Dose: 50 mg, 1 times / day Route: oral Route: steady-state Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21223356 Page: p.912	healthy, ADULT n = 19 Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Population Size: 19 Sources: https://pubmed.ncbi.nlm.nih.gov/21223356 Page: p.912	Sources: https://pubmed.ncbi.nlm.nih.gov/21223356 Page: p.912
35 mg 1 times / day multiple, oral Studied dose Dose: 35 mg, 1 times / day Route: oral Route: multiple Dose: 35 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20043816 Page: p.382	unhealthy, ADULT n = 121 Health Status: unhealthy Condition: Alzheimer disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 121 Sources: https://pubmed.ncbi.nlm.nih.gov/20043816 Page: p.382	Disc. AE: Ischemic stroke... AEs leading to discontinuation/dose reduction: Ischemic stroke (grade 2, 0.8%) Sources: https://pubmed.ncbi.nlm.nih.gov/20043816 Page: p.382

AEs

AE	Significance	Dose	Population
Ischemic stroke	grade 2, 0.8% Disc. AE	35 mg 1 times / day multiple, oral Studied dose Dose: 35 mg, 1 times / day Route: oral Route: multiple Dose: 35 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20043816 Page: p.382	unhealthy, ADULT n = 121 Health Status: unhealthy Condition: Alzheimer disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 121 Sources: https://pubmed.ncbi.nlm.nih.gov/20043816 Page: p.382

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 1537

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=363680156	inconclusive [IC50 37.9083 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=363680156	inconclusive [IC50 6.0081 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/gene/1559	yes [IC50 0.3379 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363680156	no

PubMed

Title	Date	PubMed
Double-blind, controlled phase II study of a 5-HT6 receptor antagonist, SB-742457, in Alzheimer's disease.	2010 Aug	20043816
SB-742457 and donepezil in Alzheimer disease: a randomized, placebo-controlled study.	2011 May	20872778
Effects of risperidone, clozapine and the 5-HT6 antagonist GSK-742457 on PCP-induced deficits in reversal learning in the two-lever operant task in male Sprague Dawley rats.	2013 May 1	23384714

Patents

Sample Use Guides

In Vivo Use Guide

RVT-101 (INTEPIRDINE) at doses of 70 mg and 35 mg daily will be evaluated over a 24-week double-blind treatment period

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Fri Dec 15 18:07:34 UTC 2023` Edited by `admin` on `Fri Dec 15 18:07:34 UTC 2023`
Record UNII	2IOB2M82HY
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

INTEPIRDINE

Official Name

English

GSK742457

Code

English

Intepirdine [WHO-DD]

Common Name

English

3-PHENYLSULFONYL-8-(PIPERAZIN-1-YL)QUINOLINE

Systematic Name

English

INTEPIRDINE [USAN]

Common Name

English

RVT-101

Code

English

GSK-742457

Code

English

QUINOLINE, 3-(PHENYLSULFONYL)-8-(1-PIPERAZINYL)-

Systematic Name

English

intepirdine [INN]

Common Name

English

SB-742457

Code

English

Code System Code Type Description

USAN

DE-64