Expert opinion on drug discovery
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Expert Opin Drug Discov · Aug 2020
Review Comparative StudyThe preclinical discovery and development of the combination of ivacaftor + tezacaftor used to treat cystic fibrosis.
Cystic Fibrosis (CF) is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. The most common mutation, F508del, induces protein misprocessing and loss of CFTR function. The discovery through in vitro studies of the CFTR correctors (i.e. lumacaftor, tezacaftor) that partially rescue the misprocessing of F508del-CFTR with the potentiator ivacaftor is promising in giving an unprecedented clinical benefit in affected patients. ⋯ CF patient-derived tissue models are being explored to determine donor-specific response to current approved and future novel CFTR modulators for F508del and other rare mutations. The discovery and validation of biomarkers of CFTR modulation will complement these studies in the long term and in real-life world.
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Expert Opin Drug Discov · Aug 2020
ReviewIn vivo near-infrared fluorescent optical imaging for CNS drug discovery.
In vivo imaging technologies have become integral and essential component of drug discovery, development, and clinical assessment for central nervous system (CNS) diseases. Near-infrared (NIR) fluorescence imaging in the range of 650-950 nm is widely used for pre-clinical in vivo imaging studies. The recent expansion of NIR imaging into the shortwave infrared (SWIR, 1000-1700 nm) window enabled improvements in tissue penetration and resolution required for anatomical, dynamic, and molecular neuroimaging with high potential for clinical translation. ⋯ Propelled through concomitant technological advancements in imaging instrumentation, algorithms and new SWIR emitters, SWIR imaging has addressed key barriers to optical imaging modalities used in pre-clinical studies addressing the CNS. Development of biocompatible SWIR emitters and adoption of SWIR into multi-modal imaging modalities promise to rapidly advance optical imaging into translational studies and clinical applications.