Delving into the Latest Updates on GSK-2556286 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

Rv1625c

Mechanism

Rv1625c modulators

Therapeutic Areas

Infectious Diseases

Active Indication

Tuberculosis

Inactive Indication-

Originator Organization

GSK Plc

Active Organization

GSK Plc

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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This is a first time in human (FTIH) study to evaluate the safety, tolerability and pharmacokinetics (PK) of single and repeat ascending doses of GSK2556286 in healthy adult participants. Food effect (FE) cohorts will investigate the influence of food on the PK of GSK2556286. The study will be conducted in two parts. Part A will be a single ascending dose (SAD) including up to 11 cohorts (Cohort 1A to cohort 11A) and Part B will be a multiple ascending dose (MAD), including up to 4 cohorts (Cohort 1B to cohort 4B).

Start Date30 Oct 2020

Sponsor / Collaborator

GSK Plc

100 Clinical Results associated with GSK-2556286

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100 Translational Medicine associated with GSK-2556286

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100 Patents (Medical) associated with GSK-2556286

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4

Literatures (Medical) associated with GSK-2556286

03 Apr 2024·Antimicrobial Agents and Chemotherapy

Bactericidal and sterilizing activity of novel regimens combining bedaquiline or TBAJ-587 with GSK2556286 and TBA-7371 in a mouse model of tuberculosis

Article

Author: Barros-Aguirre, David ; Li, Si-Yang ; Ballell, Lluís ; Jimenez-Navarro, Elena ; Converse, Paul J ; Mdluli, Khisimuzi ; Nuermberger, Eric L ; Upton, Anna M ; Betoudji, Fabrice ; Soni, Heena ; Tyagi, Sandeep ; Fotouhi, Nader

ABSTRACTThe combination of bedaquiline, pretomanid, and linezolid (BPaL) has become a preferred regimen for treating multidrug- and extensively drug-resistant tuberculosis (TB). However, treatment-limiting toxicities of linezolid and reports of emerging bedaquiline and pretomanid resistance necessitate efforts to develop new short-course oral regimens. We recently found that the addition of GSK2556286 increases the bactericidal and sterilizing activity of BPa-containing regimens in a well-established BALB/c mouse model of tuberculosis. Here, we used this model to evaluate the potential of new regimens combining bedaquiline or the more potent diarylquinoline TBAJ-587 with GSK2556286 and the DprE1 inhibitor TBA-7371, all of which are currently in early-phase clinical trials. We found the combination of bedaquiline, GSK2556286, and TBA-7371 to be more active than the first-line regimen and nearly as effective as BPaL in terms of bactericidal and sterilizing activity. In addition, we found that GSK2556286 and TBA-7371 were as effective as pretomanid and the novel oxazolidinone TBI-223 when either drug pair was combined with TBAJ-587 and that the addition of GSK2556286 increased the bactericidal activity of the TBAJ-587, pretomanid, and TBI-223 combination. We conclude that GSK2556286 and TBA-7371 have the potential to replace pretomanid, an oxazolidinone, or both components, in combination with bedaquiline or TBAJ-587.

24 Jan 2023·Antimicrobial Agents and Chemotherapy

Cyclic AMP-Mediated Inhibition of Cholesterol Catabolism in Mycobacterium tuberculosis by the Novel Drug Candidate GSK2556286

Article

Author: Ballell, Lluís ; Montague, Christine R. ; Wilburn, Kaley M. ; Grigg, Jason C. ; Brown, Kirstin L. ; Sanz, Olalla ; Pérez-Herrán, Esther ; Eltis, Lindsay D. ; Barros, David ; VanderVen, Brian C.

Despite the deployment of combination tuberculosis (TB) chemotherapy, efforts to identify shorter, nonrelapsing treatments have resulted in limited success. Recent evidence indicates that GSK2556286 (GSK286), which acts via Rv1625c, a membrane-bound adenylyl cyclase in Mycobacterium tuberculosis , shortens treatment in rodents relative to standard of care drugs.

21 Jun 2022·Antimicrobial Agents and Chemotherapy

GSK2556286 Is a Novel Antitubercular Drug Candidate Effective In Vivo with the Potential To Shorten Tuberculosis Treatment

Article

Author: Esquivias, Jorge ; Bates, Robert H. ; Tasneen, Rokeya ; Besra, Gurdyal S. ; Alonso, Marta ; Cammack, Nicholas C. ; Rullas-Trincado, Joaquin ; Robertson, Gregory T. ; Converse, Paul J. ; Nuermberger, Eric L. ; Li, Si-Yang ; Barros, David ; Siles, Juan Miguel ; Martínez-Martínez, Maria Santos ; Urones, Beatriz ; Boyle, Gary W. ; Soni, Heena ; Ballell, Lluís ; Fotouhi, Nader ; Escribano, Jaime ; Sanz, Olalla ; Abrahams, Katherine A. ; Turner, Sam ; Pérez-Herrán, Esther ; Tyagi, Sandeep ; Lelievre, Joel ; Upton, Anna M. ; Maher-Edwards, Gareth ; Mdluli, Khisimuzi ; Boshoff, Helena I. ; Jiménez, Elena

As a result of a high-throughput compound screening campaign using Mycobacterium tuberculosis -infected macrophages, a new drug candidate for the treatment of tuberculosis has been identified. GSK2556286 inhibits growth within human macrophages (50% inhibitory concentration [IC 50 ] = 0.07 μM), is active against extracellular bacteria in cholesterol-containing culture medium, and exhibits no cross-resistance with known antitubercular drugs.

100 Deals associated with GSK-2556286

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