A5078010008- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Eosinophilic Disorders and Syndromes
- Cancer-related gene regulation
- Sarcoidosis and Beryllium Toxicity Research
- Protein Tyrosine Phosphatases
- Neonatal Respiratory Health Research
- Ubiquitin and proteasome pathways
- Wnt/β-catenin signaling in development and cancer
- Virus-based gene therapy research
- Platelet Disorders and Treatments
- Inhalation and Respiratory Drug Delivery
- Pulmonary Hypertension Research and Treatments
- Pleural and Pulmonary Diseases
- Barrier Structure and Function Studies
- Cell Adhesion Molecules Research
- Protein Kinase Regulation and GTPase Signaling
GlaxoSmithKline (United Kingdom)
2016-2021
Age UK
2002
Research Triangle Park Foundation
2000
Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal of all fibrotic conditions with no curative therapies. Common pathomechanisms between IPF cancer are increasingly recognised, including dysfunctional pan-PI3 kinase (PI3K) signalling as a driver aberrant proliferative responses. GSK2126458 novel, potent, PI3K/mammalian target rapamycin (mTOR) inhibitor which has recently completed phase I trials in oncology setting. Our aim was to establish scientific dosing...
Phosphatidylinositol 3-kinases (PI3Ks) and mammalian target of rapamycin (mTOR) play a role in the pathogenesis idiopathic pulmonary fibrosis (IPF). Omipalisib (GSK2126458) is potent inhibitor PI3K/mTOR. A randomised, placebo-controlled, double-blind, repeat dose escalation, experimental medicine study omipalisib subjects with IPF was conducted ( NCT01725139 ) to test safety, tolerability, pharmacokinetics pharmacodynamics. dosed at 0.25 mg, 1 mg 2 twice daily for 8 days four cohorts...
Abstract The αvβ6 integrin plays a key role in the activation of transforming growth factor-β (TGFβ), pro-fibrotic mediator that is pivotal to development idiopathic pulmonary fibrosis (IPF). We identified selective small molecule RGD-mimetic, GSK3008348, and profiled it range disease relevant pre-clinical systems. To understand relationship between target engagement inhibition fibrosis, we measured pharmacodynamic disease-related end points. Here, report, GSK3008348 binds with high affinity...
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Tight junctions (TJ) are essential components of polarized epithelia, and E-cadherin is important for their formation maintenance. The bronchial epithelial cell line, 16HBE14o- expresses E- P-cadherin, but not N-cadherin. P-cadherin levels changed during culture, the former increasing after confluence, latter were markedly reduced. All detectable was bound to g - n -catenins. We investigated involvement with integrity using an specific, function-blocking antibody, SHE78-7....