Matches in SemOpenAlex for { <https://semopenalex.org/work/W2469138040> ?p ?o ?g. }
Showing items 1 to 76 of
76
with 100 items per page.
- W2469138040 abstract "Cystic Fibrosis (CF) is a life-threatening autosomal recessive disease affecting 1:3600 children born in Canada. CF is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) chloride channel. The most common disease causing mutation is a deletion of residue F508, resulting in a structurally compromised protein which is retained in the endoplasmic reticulum and targeted for proteasomal degradation. Therapeutic strategies currently being pursued to alleviate the afflictions caused by this and other mutants include the use of corrector compounds to modify the surface expression of the channel, and potentiator compounds to increase cAMP-mediated channel activity. Despite the discovery of a number of small molecules affecting CFTR, much is still unknown about the nature of these interactions. This thesis contains the investigation of two potentiators: VRT-532 and VX-770, and two correctors VX-809 and C18. We assessed the consequences of interactions with these drugs on CFTR channel activity, ATPase activity and phosphorylation. We demonstrated that VRT-532 binds directly to mutant CFTR to modify its channel and ATPase activity. VX-770, known to bind directly to CFTR, can stimulate channel activity in the absence of cAMP stimulation in baby hamster kidney (BHK) cells. Correctors VX-809 and C18, based off the same molecular scaffold, are both capable of acutely augmenting cAMP-stimulated channel activity, providing evidence for potentiator activities in these compounds. Quantitative mass spectrometry (MS) techniques demonstrate a defect in phosphorylation at Ser-660 in the regulatory (R) domain in the major mutant. Treatment with C18 was unable to repair this defect. These novel findings regarding interactions between several small molecules and CFTR contributes to the understanding of the mechanism of action of these compounds, and will help identify how they may be modified for greater efficacy to improve the treatment of CF disease.%%%%PhD" @default.
- W2469138040 created "2016-07-22" @default.
- W2469138040 creator A5080551487 @default.
- W2469138040 date "2014-04-01" @default.
- W2469138040 modified "2023-09-23" @default.
- W2469138040 title "Insights into the Interactions between CFTR and Small Molecule Modulators" @default.
- W2469138040 cites W1955928122 @default.
- W2469138040 cites W1969697265 @default.
- W2469138040 cites W1989182163 @default.
- W2469138040 cites W2004844038 @default.
- W2469138040 cites W2051015480 @default.
- W2469138040 cites W2082006641 @default.
- W2469138040 hasPublicationYear "2014" @default.
- W2469138040 type Work @default.
- W2469138040 sameAs 2469138040 @default.
- W2469138040 citedByCount "0" @default.
- W2469138040 crossrefType "dissertation" @default.
- W2469138040 hasAuthorship W2469138040A5080551487 @default.
- W2469138040 hasConcept C104317684 @default.
- W2469138040 hasConcept C11960822 @default.
- W2469138040 hasConcept C143065580 @default.
- W2469138040 hasConcept C145822097 @default.
- W2469138040 hasConcept C158617107 @default.
- W2469138040 hasConcept C164718446 @default.
- W2469138040 hasConcept C185592680 @default.
- W2469138040 hasConcept C2776938444 @default.
- W2469138040 hasConcept C2777893369 @default.
- W2469138040 hasConcept C2778428886 @default.
- W2469138040 hasConcept C501734568 @default.
- W2469138040 hasConcept C54355233 @default.
- W2469138040 hasConcept C55493867 @default.
- W2469138040 hasConcept C86803240 @default.
- W2469138040 hasConcept C95444343 @default.
- W2469138040 hasConcept C98274493 @default.
- W2469138040 hasConceptScore W2469138040C104317684 @default.
- W2469138040 hasConceptScore W2469138040C11960822 @default.
- W2469138040 hasConceptScore W2469138040C143065580 @default.
- W2469138040 hasConceptScore W2469138040C145822097 @default.
- W2469138040 hasConceptScore W2469138040C158617107 @default.
- W2469138040 hasConceptScore W2469138040C164718446 @default.
- W2469138040 hasConceptScore W2469138040C185592680 @default.
- W2469138040 hasConceptScore W2469138040C2776938444 @default.
- W2469138040 hasConceptScore W2469138040C2777893369 @default.
- W2469138040 hasConceptScore W2469138040C2778428886 @default.
- W2469138040 hasConceptScore W2469138040C501734568 @default.
- W2469138040 hasConceptScore W2469138040C54355233 @default.
- W2469138040 hasConceptScore W2469138040C55493867 @default.
- W2469138040 hasConceptScore W2469138040C86803240 @default.
- W2469138040 hasConceptScore W2469138040C95444343 @default.
- W2469138040 hasConceptScore W2469138040C98274493 @default.
- W2469138040 hasLocation W24691380401 @default.
- W2469138040 hasOpenAccess W2469138040 @default.
- W2469138040 hasPrimaryLocation W24691380401 @default.
- W2469138040 hasRelatedWork W1527010259 @default.
- W2469138040 hasRelatedWork W1574853868 @default.
- W2469138040 hasRelatedWork W1597608099 @default.
- W2469138040 hasRelatedWork W1763513358 @default.
- W2469138040 hasRelatedWork W1991977085 @default.
- W2469138040 hasRelatedWork W2003428468 @default.
- W2469138040 hasRelatedWork W2027207647 @default.
- W2469138040 hasRelatedWork W2034872994 @default.
- W2469138040 hasRelatedWork W2139475301 @default.
- W2469138040 hasRelatedWork W2148311403 @default.
- W2469138040 hasRelatedWork W2151684918 @default.
- W2469138040 hasRelatedWork W2162989130 @default.
- W2469138040 hasRelatedWork W2294720611 @default.
- W2469138040 hasRelatedWork W2801240372 @default.
- W2469138040 hasRelatedWork W2954615196 @default.
- W2469138040 hasRelatedWork W2973515858 @default.
- W2469138040 hasRelatedWork W3134615639 @default.
- W2469138040 hasRelatedWork W3172068665 @default.
- W2469138040 hasRelatedWork W1603944310 @default.
- W2469138040 isParatext "false" @default.
- W2469138040 isRetracted "false" @default.
- W2469138040 magId "2469138040" @default.
- W2469138040 workType "dissertation" @default.