GSK2556286 / GSK - LARVOL DELTA

A Study to Evaluate Safety, Tolerability and Pharmacokinetics of GSK2556286 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=92 | Terminated | Sponsor: GlaxoSmithKline | Trial completion date: Jul 2024 ➔ Nov 2024 | Recruiting ➔ Terminated | Trial primary completion date: Jul 2024 ➔ Nov 2024; A decision to stop the study was made by the site and GSK project team based on pre-defined stopping criteria in the protocol

Trial completion date • Trial primary completion date • Trial termination • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

In Silico ADMET Studies, Molecular Docking and Molecular Dynamics Simulation of Thiadiazole Derivatives for the Identification of Putative HsaA Monooxygenase Inhibitors. (PubMed, Curr Med Chem) - "All these findings demonstrated that AK05 and AK13 could be used as potent compounds for the development of HsaA monooxygenase inhibitors."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Pyrimidine-Based Compounds in Tuberculosis Management: A Review of their Biological and Medicinal Importance. (PubMed, Med Chem) - "Three medications-GSK-286, TBA- 7371, and SPR-720 are now undergoing clinical testing. This study aims to emphasize the structural variety of anti-tuberculosis pyrimidine-containing compounds by providing an overview of current developments in drug discovery investigations."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Bactericidal and sterilizing activity of novel regimens combining bedaquiline or TBAJ-587 with GSK2556286 and TBA-7371 in a mouse model of tuberculosis. (PubMed, Antimicrob Agents Chemother) - "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."

Journal • Preclinical • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

A minimal PBPK model to accelerate preclinical development of drugs against tuberculosis. (PubMed, Front Pharmacol) - " The model has been successfully tested and validated against 11 anti-TB compounds-rifampicin, rifapentine, pyrazinamide, ethambutol, isoniazid, moxifloxacin, delamanid, pretomanid, bedaquiline, OPC-167832, GSK2556286 - showing robust predictability power in recapitulating PK dynamics in mice. Discrepancies in plasma and lung levels for the latest BPaMZ and HPMZ regimens have been analyzed in terms of their impact on preclinical experiment design and on PK/PD indices. The framework we developed requires limited drug- and species-specific information to reconstruct accurate PK dynamics, delivering a unified viewpoint on anti-TB drug distribution at the site-of-action and a flexible fit-for-purpose tool to accelerate model-informed drug design pipelines and facilitate translation into the clinic."

Journal • Preclinical • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

A Study to Evaluate Safety, Tolerability and Pharmacokinetics of GSK2556286 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=120 | Recruiting | Sponsor: GlaxoSmithKline | Trial completion date: Dec 2023 ➔ Jul 2024 | Trial primary completion date: Dec 2023 ➔ Jul 2024

Trial completion date • Trial primary completion date • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

A Study to Evaluate Safety, Tolerability and Pharmacokinetics of GSK2556286 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=120 | Recruiting | Sponsor: GlaxoSmithKline | Trial completion date: Jun 2023 ➔ Dec 2023 | Trial primary completion date: Jun 2023 ➔ Dec 2023

Trial completion date • Trial primary completion date • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Cyclic AMP-Mediated Inhibition of Cholesterol Catabolism in Mycobacterium tuberculosis by the Novel Drug Candidate GSK2556286. (PubMed, Antimicrob Agents Chemother) - "Together, these data establish that GSK286 is an Rv1625c agonist and sheds light on how cAMP signaling can be manipulated as a novel antibiotic strategy to shorten TB treatments. Nevertheless, the detailed mechanism of action of these compounds remains to be elucidated."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Pyrimidine derivatives with antitubercular activity. (PubMed, Eur J Med Chem) - "Small molecules with antitubercular activity containing the pyrimidine motif in their structure have gained more attention after three drugs, namely GSK 2556286 (GSK-286), TBA-7371 and SPR720, have entered clinical trials. In the first part, the review discusses the pyrimidine compounds according to their targets, pinpointing the structure-activity relationships of each pyrimidine family. The second part of this review is concentrated on antitubercular pyrimidine derivatives with a yet unexplored or speculative target, dividing the compounds according to their structural types."

Journal • Review • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

GSK2556286 Is a Novel Antitubercular Drug Candidate Effective In Vivo with the Potential To Shorten Tuberculosis Treatment. (PubMed, Antimicrob Agents Chemother) - P1 | "These features indicate a compound with a novel mode of action, although still not fully defined, that is effective against both multidrug-resistant (MDR) or extensively drug-resistant (XDR) and drug-sensitive (DS) M. tuberculosis with the potential to shorten the duration of treatment in novel combination drug regimens. (This study has been registered at ClinicalTrials.gov under identifier NCT04472897)."

Journal • Preclinical • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

A Study to Evaluate Safety, Tolerability and Pharmacokinetics of GSK2556286 in Healthy Adult Participants (clinicaltrials.gov) - P1; N=96; Recruiting; Sponsor: GlaxoSmithKline; Trial completion date: May 2022 ➔ Jun 2023; Trial primary completion date: May 2022 ➔ Jun 2023

Clinical • Trial completion date • Trial primary completion date • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

A Study to Evaluate Safety, Tolerability and Pharmacokinetics of GSK2556286 in Healthy Adult Participants (clinicaltrials.gov) - P1; N=96; Recruiting; Sponsor: GlaxoSmithKline; Not yet recruiting ➔ Recruiting; Trial completion date: Nov 2021 ➔ Apr 2022; Trial primary completion date: Nov 2021 ➔ Apr 2022

Clinical • Enrollment open • Trial completion date • Trial primary completion date • Infectious Disease • Respiratory Diseases • Tuberculosis

A Study to Evaluate Safety, Tolerability and Pharmacokinetics of GSK2556286 in Healthy Adult Participants (clinicaltrials.gov) - P1; N=96; Not yet recruiting; Sponsor: GlaxoSmithKline

Clinical • New P1 trial • Infectious Disease • Tuberculosis