Translational Pharmacology in Glaucoma Neuroprotection

2016 ◽  
pp. 209-230 ◽  
Author(s):  
Leonard A. Levin
Keyword(s):  
Translational Pharmacology

scholarly journals Pharmacodynamic Model of Sodium–Glucose Transporter 2 (SGLT2) Inhibition: Implications for Quantitative Translational Pharmacology

2011 ◽  
Vol 13 (4) ◽  
pp. 576-584 ◽  
Author(s):  
Tristan S. Maurer ◽  
Avijit Ghosh ◽  
Nahor Haddish-Berhane ◽  
Aarti Sawant-Basak ◽  
Carine M. Boustany-Kari ◽  
...  
Keyword(s):  
Glucose Transporter ◽  
Pharmacodynamic Model ◽  
Glucose Transporter 2 ◽  
Translational Pharmacology ◽  
Sglt2 Inhibition

Use of real‐world evidence in translational pharmacology research

2021 ◽  
Author(s):  
Mathieu Charvériat ◽  
Stephan J. Darmoni ◽  
Vincent Lafon ◽  
Nicholas Moore ◽  
Régis Bordet ◽  
...  
Keyword(s):  
Real World ◽  
Real World Evidence ◽  
Translational Pharmacology

Diabetes and Phytopharmaceuticals: Translational Pharmacology Perspective

2018 ◽  
pp. 201-223
Author(s):  
Priyanka Ingle-Jadhav ◽  
Trupti Rajkumar Angolkar ◽  
Ginpreet Kaur
Keyword(s):  
Translational Pharmacology

scholarly journals Translational pharmacology of an inhaled small molecule αvβ6 integrin inhibitor for idiopathic pulmonary fibrosis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Alison E. John ◽  
Rebecca H. Graves ◽  
K. Tao Pun ◽  
Giovanni Vitulli ◽  
Ellen J. Forty ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Small Molecule ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Lung Epithelial Cells ◽  
Tgfβ Signaling ◽  
Lung Epithelial ◽  
Translational Pharmacology ◽  
Αvβ6 Integrin

Abstract The αvβ6 integrin plays a key role in the activation of transforming growth factor-β (TGFβ), a pro-fibrotic mediator that is pivotal to the development of idiopathic pulmonary fibrosis (IPF). We identified a selective small molecule αvβ6 RGD-mimetic, GSK3008348, and profiled it in a range of disease relevant pre-clinical systems. To understand the relationship between target engagement and inhibition of fibrosis, we measured pharmacodynamic and disease-related end points. Here, we report, GSK3008348 binds to αvβ6 with high affinity in human IPF lung and reduces downstream pro-fibrotic TGFβ signaling to normal levels. In human lung epithelial cells, GSK3008348 induces rapid internalization and lysosomal degradation of the αvβ6 integrin. In the murine bleomycin-induced lung fibrosis model, GSK3008348 engages αvβ6, induces prolonged inhibition of TGFβ signaling and reduces lung collagen deposition and serum C3M, a marker of IPF disease progression. These studies highlight the potential of inhaled GSK3008348 as an anti-fibrotic therapy.

Target Validation Using PROTACs: Applying the Four Pillars Framework

2020 ◽  
pp. 247255522097958
Author(s):  
Radosław P. Nowak ◽  
Lyn H. Jones
Keyword(s):  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Experimental Methods ◽  
Pharmacological Effects ◽  
Target Validation ◽  
Chemical Probes ◽  
Structure Activity ◽  
Site Of Action ◽  
Translational Pharmacology ◽  
Orally Bioavailable

Proteolysis targeting chimeras (PROTACs) are heterobifunctional compounds that recruit the E3 ubiquitin ligase machinery to proteins of interest, resulting in their ubiquitination and subsequent proteasomal degradation. Targeted protein degradation has generated considerable interest in drug discovery because inhibition of one particular function of a protein often does not deliver the therapeutic efficacy that results from whole-protein depletion. However, the physicochemistry and intrinsically complex pharmacology of PROTACs present challenges, particularly for the development of orally bioavailable drugs. Here we describe the application of a translational pharmacology framework (called the four pillars) to expedite PROTAC development by informing pharmacokinetic–pharmacodynamic (PKPD) understanding and helping elucidate structure–activity relationships. Experimental methods are reviewed that help illuminate exposure of the drug or probe at the site of action (pillar 1) and engagement of its target(s) (pillar 2) that drive functional pharmacological effects (pillar 3) resulting in modulation of a relevant phenotype (pillar 4). We hope the guidance will be useful to those developing targeted protein degraders and help establish PROTAC molecules as robust target validation chemical probes.

scholarly journals A3 TRANSLATIONAL PHARMACOLOGY STRATEGY TO EVALUATE MMP-13 INHIBITORS FOR THE TREATMENT OF OA; USE OF BIOMARKERS

2008 ◽  
Vol 16 ◽  
pp. S14 ◽  
Author(s):  
T. Sunyer ◽  
L.E. Vickery ◽  
O.V. Nemirovskiy ◽  
S.L. Settle ◽  
A. Bendele ◽  
...  
Keyword(s):  
Translational Pharmacology
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