GSK3494245 / GSK - LARVOL DELTA

Safety, Tolerability and Pharmacokinetics (PK) Investigation of GSK3494245 in Healthy Participants (clinicaltrials.gov) - P1 | N=59 | Completed | Sponsor: GlaxoSmithKline | Recruiting ➔ Completed | Trial completion date: Jun 2024 ➔ Jan 2024 | Trial primary completion date: Jun 2024 ➔ Jan 2024

Trial completion • Trial completion date • Trial primary completion date • Infectious Disease

Structure-Guided Design and Synthesis of a Pyridazinone Series of Trypanosoma cruzi Proteasome Inhibitors. (PubMed, J Med Chem) - "We previously reported on the discovery of GSK3494245/DDD01305143, a preclinical candidate for visceral leishmaniasis which acted through inhibition of the Leishmania proteasome...Alongside this, optimization of the absorption, distribution, metabolism, and excretion (ADME) properties afforded a suitable compound for mouse efficacy studies. The outcome of these studies is discussed, alongside future plans to further understand the series and its potential to deliver a new treatment for Chagas disease."

Journal • Infectious Disease

Safety, Tolerability and Pharmacokinetics (PK) Investigation of GSK3494245 in Healthy Participants (clinicaltrials.gov) - P1 | N=54 | Recruiting | Sponsor: GlaxoSmithKline | Trial completion date: Apr 2023 ➔ Jun 2024 | Trial primary completion date: Apr 2023 ➔ Jun 2024 | Suspended ➔ Recruiting

Enrollment open • Trial completion date • Trial primary completion date • Infectious Disease

Safety, Tolerability and Pharmacokinetics (PK) Investigation of GSK3494245 in Healthy Participants (clinicaltrials.gov) - P1 | N=54 | Recruiting | Sponsor: GlaxoSmithKline | Suspended ➔ Recruiting

Enrollment open • Infectious Disease

Safety, Tolerability and Pharmacokinetics (PK) Investigation of GSK3494245 in Healthy Participants (clinicaltrials.gov) - P1 | N=54 | Suspended | Sponsor: GlaxoSmithKline | Recruiting ➔ Suspended

Trial suspension • Infectious Disease

Safety, Tolerability and Pharmacokinetics (PK) Investigation of GSK3494245 in Healthy Participants (clinicaltrials.gov) - P1 | N=54 | Recruiting | Sponsor: GlaxoSmithKline | Suspended ➔ Recruiting | Trial completion date: Oct 2022 ➔ Apr 2023 | Trial primary completion date: Oct 2022 ➔ Apr 2023

Enrollment open • Trial completion date • Trial primary completion date • Infectious Disease

Small molecules as kinetoplastid specific proteasome inhibitors for Leishmaniasis: a patent review from 1998 to 2021. (PubMed, Expert Opin Ther Pat) - "LXE408 and GSK3494245 are two KSPIs in different phases of clinical trials. The KSPIs are promising next-generation orally active patient compliant drugs against kinetoplastid diseases, including leishmaniasis. However, the main challenge to discover the KSPIs will be the resistance development and their selectivity against the proteasome of eukaryotic cells."

Journal • Review • Infectious Disease

Safety, Tolerability and Pharmacokinetics (PK) Investigation of GSK3494245 in Healthy Participants (clinicaltrials.gov) - P1; N=54; Suspended; Sponsor: GlaxoSmithKline; Trial completion date: May 2022 ➔ Oct 2022; Recruiting ➔ Suspended; Trial primary completion date: May 2022 ➔ Oct 2022

Clinical • Trial completion date • Trial primary completion date • Trial suspension • Infectious Disease

Safety, Tolerability and Pharmacokinetics (PK) Investigation of GSK3494245 in Healthy Participants (clinicaltrials.gov) - P1; N=54; Recruiting; Sponsor: GlaxoSmithKline; Trial completion date: Jun 2021 ➔ May 2022; Trial primary completion date: Jun 2021 ➔ May 2022

Clinical • Trial completion date • Trial primary completion date • Infectious Disease

Scaffold-Hopping Strategy on a Series of Proteasome Inhibitors Led to a Preclinical Candidate for the Treatment of Visceral Leishmaniasis. (PubMed, J Med Chem) - "We previously reported on the discovery of GSK3494245/DDD01305143 (1) as a preclinical candidate for VL and, herein, we report on the medicinal chemistry program that led to its identification...The work on the original scaffold failed to lead to developable compounds, so an extensive scaffold-hopping exercise involving medicinal chemistry design, in silico profiling, and subsequent synthesis was utilized, leading to the preclinical candidate. The compound was shown to act via proteasome inhibition, and we report on the modeling of different scaffolds into a cryo-EM structure and the impact this has on our understanding of the series' structure-activity relationships."

Journal • Preclinical • Infectious Disease

Safety, Tolerability and Pharmacokinetics (PK) Investigation of GSK3494245 in Healthy Participants (clinicaltrials.gov) - P1; N=54; Recruiting; Sponsor: GlaxoSmithKline; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Infectious Disease