Delving into the Latest Updates on GSK-2018682 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

S1PR1

Mechanism

S1PR1 agonists(Sphingosine 1-phosphate receptor Edg-1 agonists)

Therapeutic Areas

Immune System DiseasesNervous System DiseasesOther Diseases

Active Indication-

Inactive Indication

Multiple Sclerosis, Relapsing-Remitting

Originator Organization

GSK Plc

Active Organization-

Inactive Organization

GSK Plc

Drug Highest PhasePendingPhase 1

First Approval Date-

Regulation-

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Structure

Molecular FormulaC22H21ClN4O4

InChIKeyNFIGDBFIDKDNIG-UHFFFAOYSA-N

CAS Registry1034688-30-6

GSK2018682 is a potent and selective agonist for the sphingosine-1- phosphate receptor subtype 1 (S1P1) with the potential to be an effective treatment for multiple sclerosis (MS). The immunomodulatory properties of GSK2018682 are related to functional antagonism of S1P1 on lymphocytes, resulting in sequestration of lymphocytes within the lymphoid organs, rendering them incapable of migrating to sites of inflammation and leading to lymphopenia. Orally administered GSK2018682 is very effective in murine experimental autoimmune encephalomyelitis (EAE), an animal model of human MS. This study will assess the relative bioavailability of different oral formulations of GSK2018682 in healthy volunteers. A tablet formulation is desired for progression into future clinical safety and efficacy studies as the current capsule formulation is not suited to large scale manufacture. The information obtained in this study will help to establish the optimal dosing form for future studies, and also determine the effect of food on the pharmacokinetics of GSK2018682.

Start Date22 Dec 2010

Sponsor / Collaborator

GSK Plc

NCT01431937 / CompletedPhase 1

A Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Repeat Ascending Doses of GSK2018682 (S1P1 Agonist) in Healthy Volunteers

The study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of repeat ascending doses of GSK2018682. The study will also provide further evidence of the potential therapeutic dose-range by measuring the inhibitory effect of GSK2018682 on Absolute Lymphocyte Counts (ALC).

Start Date10 Oct 2010

Sponsor / Collaborator

GSK Plc

NCT01387217 / CompletedPhase 1

A Single-blind, Placebo-controlled, Two Part Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Doses of GSK2018682 in Healthy Volunteers

This protocol describes the first administration of GSK2018682 to humans. The study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single ascending doses of GSK2018682. The study will also provide preliminary evidence of the potential therapeutic dose-range by measuring the inhibitory effect of GSK2018682 on total lymphocyte counts.

Start Date21 May 2010

Sponsor / Collaborator

GSK Plc

100 Clinical Results associated with GSK-2018682

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100 Translational Medicine associated with GSK-2018682

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100 Patents (Medical) associated with GSK-2018682

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4

Literatures (Medical) associated with GSK-2018682

01 Jan 2018·Biomedical ChromatographyQ4 · MEDICINE

A review of bioanalytical quantitative methods for selected sphingosine 1‐phosphate receptor modulators

Q4 · MEDICINE

Review

Author: Rais, Rana ; Srinivas, Nuggehally R. ; Dash, Ranjeet Prasad

AbstractSphingosine 1‐phosphate (S1P1) modulators provide an emerging therapeutic approach for various autoimmune disorders such as multiple sclerosis and psoriasis. Fingolimod is the first approved orally active, selective and potent drug of this class. Other drugs belonging to this class include siponimod, ponesimod, ceralifimod, amiselimod, CS‐0777 and GSK2018682. However, owing to the high protein binding, polarity and zwitter‐ionic nature of the phosphate metabolite of parent drugs, it becomes challenging to optimize the extraction method for this class of compounds. Although, there are individual published bioanalytical methods for the analysis of selected S1P1 modulators to support preclinical and clinical drug development, no extensive review compiling all the bioanalytical methods for the important drugs in the class is available. Thus, we attempted to prepare a comprehensive review on various bioanalytical methods for selected S1P1 modulators which will provide all the relevant bioanalytical information as required by bioanalytical researchers. This review focuses on the various liquid chromatography with tandem mass spectrometry methods that have been used to quantify S1P1 modulators in various biological matrices. Extraction methods included liquid–liquid extraction, solid‐phase extraction and one‐step protein precipitation for extracting the analytes. This review captures key information regarding sample processing options and chromatographic/detection conditions.

01 Oct 2017·NeurotherapeuticsQ2 · MEDICINE

Sphingosine 1-Phosphate Receptor Modulators for the Treatment of Multiple Sclerosis

Q2 · MEDICINE

Review

Author: Chaudhry, Burhan Z ; Cohen, Jeffrey A ; Conway, Devon S

Sphingosine 1-phosphate receptor (S1PR) modulators possess a unique mechanism of action in the treatment of multiple sclerosis (MS). Subtype 1 of the S1PR is expressed on the surface of lymphocytes and is important in regulating egression from lymph nodes. The S1PR modulators indirectly antagonize the receptor's function leading to sequestration of lymphocytes in the lymph nodes. Fingolimod was the first S1PR modulator to receive regulatory approval for relapsing-remitting MS after 2 phase III trials demonstrated potent efficacy, safety, and tolerability. Fingolimod can cause undesirable effects as a result of its interaction with other S1PR subtypes, which are expressed in diverse tissues, including cardiac myocytes. As such, agents that more selectively target subtype 1 of the S1PR are of interest and are at various stages of development. These include ponesimod (ACT128800), siponimod (BAF312), ozanimod (RPC1063), ceralifimod (ONO-4641), GSK2018682, and MT-1303. Data from phase II trials and early results from phase III studies have been promising and will be presented in this review. Of special interest are results from the EXPAND study of siponimod, which suggest a potential role for S1PR modulators in secondary progressive MS.

01 Jul 2015·CNS DrugsQ2 · MEDICINE

Sphingosine 1-Phosphate Receptor Modulators in Multiple Sclerosis

Q2 · MEDICINE

Review

Author: Jeffrey A. Cohen ; Adnan M. Subei

Sphingosine 1-phosphate (S1P) receptor modulators possess a unique mechanism of action as disease-modifying therapy for multiple sclerosis (MS). Subtype 1 S1P receptors are expressed on the surfaces of lymphocytes and are important in regulating egression from lymph nodes. The S1P receptor modulators indirectly antagonize the receptor's function and sequester lymphocytes in lymph nodes. Fingolimod was the first S1P agent approved in the USA in 2010 for relapsing MS after two phase III trials (FREEDOMS and TRANSFORMS) demonstrated potent efficacy, and good safety and tolerability. Post-marketing experience, as well as a third phase III trial (FREEDOMS II), also showed favorable results. More selective S1P receptor agents-ponesimod (ACT128800), siponimod (BAF312), ozanimod (RPC1063), ceralifimod (ONO-4641), GSK2018682, and MT-1303-are still in relatively early stages of development, but phase I and II trials showed promising efficacy and safety. However, these observations have yet to be reproduced in phase III clinical trials.

100 Deals associated with GSK-2018682

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