GSK-356278

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H25N7O2S
Molecular Weight	439.534
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCN1N=CC2=C(NC3CCOCC3)C(=CN=C12)C4=NN=C(CC5=C(C)N=C(C)S5)O4

InChI

InChIKey=AWDJJMXJUOHGLC-UHFFFAOYSA-N

InChI=1S/C21H25N7O2S/c1-4-28-20-15(11-23-28)19(25-14-5-7-29-8-6-14)16(10-22-20)21-27-26-18(30-21)9-17-12(2)24-13(3)31-17/h10-11,14H,4-9H2,1-3H3,(H,22,25)

HIDE SMILES / InChI

Molecular Formula	C21H25N7O2S
Molecular Weight	439.534
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/28737056 | https://clinicaltrials.gov/ct2/show/NCT01573819 | https://clinicaltrials.gov/ct2/show/NCT01031186

GlaxoSmithKline is developing GSK-356278 as a selective, brain-penetrant phosphodiesterase 4 (PDE4) inhibitor that demonstrates anxiolytic and cognition-enhancing effects. Small molecule phosphodiesterase (PDE) 4 inhibitors have long been known to show therapeutic benefit in various preclinical models of psychiatric and neurologic diseases because of their ability to elevate cAMP in various cell types of the central nervous system. The drug was studied for the treatment of Huntington's disease, depressive and anxiety disorders. GSK-356278 has completed phase I clinical trials for evaluation of the safety, tolerability, and pharmacokinetics in male volunteers with the therapeutic dose for future clinical development.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Phosphodiesterase 4A 13 Target ID: CHEMBL254 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24784567	Inhibitor 8504	8.6 null [pIC50]
Phosphodiesterase 4B 11 Target ID: CHEMBL275 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24784567	Inhibitor 8504	8.8 null [pIC50]
Phosphodiesterase 4D 14 Target ID: CHEMBL288 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24784567	Inhibitor 8504	8.7 null [pIC50]

PubMed

Title	Date	PubMed
Quantification of human brain PDE4 occupancy by GSK356278: A [11C](R)-rolipram PET study.	2018-11	28737056
GSK356278, a potent, selective, brain-penetrant phosphodiesterase 4 inhibitor that demonstrates anxiolytic and cognition-enhancing effects without inducing side effects in preclinical species.	2014-07	24784567

Patents

Sample Use Guides

In Vivo Use Guide

In Dosing Session 1, the subjects will be administered 0.5 mg GSK356278 and placebo in a fasted state. In Dosing Session 2, the subjects will be administered GSK356278 (0.5 mg and 1.5 mg) and placebo in a fasted state. In Dosing Session 3, the subjects will be administered GSK356278 (1.5 mg and 4 mg) and placebo in a fasted state.

Route of Administration: Oral

Substance Class	Chemical Created by `admin` on `Mon Mar 31 21:19:11 GMT 2025` Edited by `admin` on `Mon Mar 31 21:19:11 GMT 2025`
Record UNII	1QTA9P992C
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

GSK-356278

Code

English

GSK356278

Preferred Name

English

1H-PYRAZOLO(3,4-B)PYRIDIN-4-AMINE, 5-(5-((2,4-DIMETHYL-5-THIAZOLYL)METHYL)-1,3,4-OXADIAZOL-2-YL)-1-ETHYL-N-(TETRAHYDRO-2H-PYRAN-4-YL)-

Systematic Name

English

GSK356278B

Code

English

Code System Code Type Description

EPA CompTox

DTXSID40222401