- IRAK4 INHIBITING AGENTS
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Provided are compounds of Formula (I), or pharmaceutically acceptable salts thereof, and methods for their use and production.
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Page/Page column 282
(2016/03/13)
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- Development of Fluorine-18 Labeled Metabolically Activated Tracers for Imaging of Drug Efflux Transporters with Positron Emission Tomography
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Increased activity of efflux transporters, e.g., P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), at the blood-brain barrier is a pathological hallmark of many neurological diseases, and the resulting multiple drug resistance represents a major clinical challenge. Noninvasive imaging of transporter activity can help to clarify the underlying mechanisms of drug resistance and facilitate diagnosis, patient stratification, and treatment monitoring. We have developed a metabolically activated radiotracer for functional imaging of P-gp/BCRP activity with positron emission tomography (PET). In preclinical studies, the tracer showed excellent initial brain uptake and clean conversion to the desired metabolite, although at a sluggish rate. Blocking with P-gp/BCRP modulators led to increased levels of brain radioactivity; however, dynamic PET did not show differential clearance rates between treatment and control groups. Our results provide proof-of-concept for development of prodrug tracers for imaging of P-gp/BCRP function in vivo but also highlight some challenges associated with this strategy.
- Sander, Kerstin,Galante, Eva,Gendron, Thibault,Yiannaki, Elena,Patel, Niral,Kalber, Tammy L.,Badar, Adam,Robson, Mathew,Johnson, Sean P.,Bauer, Florian,Mairinger, Severin,Stanek, Johann,Wanek, Thomas,Kuntner, Claudia,Kottke, Tim,Weizel, Lilia,Dickens, David,Erlandsson, Kjell,Hutton, Brian F.,Lythgoe, Mark F.,Stark, Holger,Langer, Oliver,Koepp, Matthias,?rstad, Erik
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p. 6058 - 6080
(2015/08/24)
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- Syntheses of fluorinated ligands to probe binding of antigenic determinants of Vibrio cholerae O:1, serotypes Inaba and Ogawa, to antibodies
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Derivatives of methyl α-glycosides of antigenic determinants of Vibrio cholerae O:1, serotypes Inaba and Ogawa, specifically fluorinated at position 2' or 4' have been synthesized by coupling the appropriately fluorinated derivatives of 3-deoxy-L-glycero-tetronic acid with the methyl α-glycosides of perosamine. The compound having the fluorine atom at position 2 was obtained by electrophilic addition of fluorine to the glycal derived from the parent antigenic determinant, serotypes Inaba, using Selectfluor((TM)) as a fluorination reagent. Copyright (C) 2000 Elsevier Science Ltd.
- Chang, Alex H.C.,Horton, Derek,Kovac, Pavol
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p. 595 - 606
(2007/10/03)
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