Potentiation of ΔF508- and G551D-CFTR-Mediated Cl- Current by Novel Hydroxypyrazolines
The most common mutation of CFTR, affecting approximately 90% of CF patients, is a deletion of phenylalanine at position 508 (F508del, ΔF508). Misfolding of ΔF508-CFTR impairs both its trafficking to the plasma membrane and its chloride channel activity. To identify small molecules that can restore...
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| creator | Park, Jinhong Khloya, Poonam Seo, Yohan Kumar, Satish Lee, Ho K Jeon, Dong-Kyu Jo, Sungwoo Sharma, Pawan K Namkung, Wan |
| description | The most common mutation of CFTR, affecting approximately 90% of CF patients, is a deletion of phenylalanine at position 508 (F508del, ΔF508). Misfolding of ΔF508-CFTR impairs both its trafficking to the plasma membrane and its chloride channel activity. To identify small molecules that can restore channel activity of ΔF508-CFTR, we synthesized and evaluated eighteen novel hydroxypyrazoline analogues as CFTR potentiators. To elucidate potentiation activities of hydroxypyrazolines for ΔF508-CFTR, CFTR activity was measured using a halide-sensitive YFP assay, Ussing chamber assay and patch-clamp technique. Compounds 7p, 7q and 7r exhibited excellent potentiation with EC50 value |
| doi_str_mv | 10.1371/journal.pone.0149131 |
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Misfolding of ΔF508-CFTR impairs both its trafficking to the plasma membrane and its chloride channel activity. To identify small molecules that can restore channel activity of ΔF508-CFTR, we synthesized and evaluated eighteen novel hydroxypyrazoline analogues as CFTR potentiators. To elucidate potentiation activities of hydroxypyrazolines for ΔF508-CFTR, CFTR activity was measured using a halide-sensitive YFP assay, Ussing chamber assay and patch-clamp technique. Compounds 7p, 7q and 7r exhibited excellent potentiation with EC50 value <10 μM. Among the compounds, 7q (a novel CFTR potentiator, CP7q) showed the highest potentiation activity with EC50 values of 0.88 ± 0.11 and 4.45 ± 0.31 μM for wild-type and ΔF508-CFTR, respectively. In addition, CP7q significantly potentiated chloride conductance of G551D-CFTR, a CFTR gating mutant; its maximal potentiation activity was 1.9 fold higher than the well-known CFTR potentiator genistein. Combination treatment with CP7q and VX-809, a corrector of ΔF508-CFTR, significantly enhanced functional rescue of ΔF508-CFTR compared with VX-809 alone. CP7q did not alter the cytosolic cAMP level and showed no cytotoxicity at the concentration showing maximum efficacy. The hydroxypyrazolines may be potential development candidates for drug therapy of cystic fibrosis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0149131</identifier><identifier>PMID: 26863533</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aminopyridines - therapeutic use ; Animals ; Bacterial Proteins - chemistry ; Benzodioxoles - therapeutic use ; Biology and Life Sciences ; Cell Line ; Cell Line, Tumor ; Cell Membrane - metabolism ; Cell Proliferation ; Channel gating ; Chemical synthesis ; Chloride ; Chloride conductance ; Chlorides ; Chlorides - chemistry ; Clinical trials ; Cyclic AMP - metabolism ; Cystic fibrosis ; Cystic Fibrosis - drug therapy ; Cystic Fibrosis - genetics ; Cystic Fibrosis Transmembrane Conductance Regulator - genetics ; Cytotoxicity ; Defects ; Epithelial Cells - cytology ; Gene Deletion ; Genistein ; Genistein - chemistry ; Humans ; Kinases ; Luminescent Proteins - chemistry ; Medicine and Health Sciences ; Membrane trafficking ; Mutation ; Nose - physiology ; Patch-Clamp Techniques ; Pharmaceutical sciences ; Pharmacy ; Phenylalanine ; Phenylalanine - genetics ; Physical Sciences ; Plasma ; Potentiation ; Proteins ; Pyrazoles - therapeutic use ; Rats ; Research and analysis methods ; Resistance ; Structure-Activity Relationship ; Sulfonamides - therapeutic use ; Toxicity</subject><ispartof>PloS one, 2016-02, Vol.11 (2), p.e0149131-e0149131</ispartof><rights>2016 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Park et al 2016 Park et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-4a1574d842f37daf52694465339fb40195f45522501e7e1c9168a8b03720ad23</citedby><cites>FETCH-LOGICAL-c526t-4a1574d842f37daf52694465339fb40195f45522501e7e1c9168a8b03720ad23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749168/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749168/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26863533$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, Jinhong</creatorcontrib><creatorcontrib>Khloya, Poonam</creatorcontrib><creatorcontrib>Seo, Yohan</creatorcontrib><creatorcontrib>Kumar, Satish</creatorcontrib><creatorcontrib>Lee, Ho K</creatorcontrib><creatorcontrib>Jeon, Dong-Kyu</creatorcontrib><creatorcontrib>Jo, Sungwoo</creatorcontrib><creatorcontrib>Sharma, Pawan K</creatorcontrib><creatorcontrib>Namkung, Wan</creatorcontrib><title>Potentiation of ΔF508- and G551D-CFTR-Mediated Cl- Current by Novel Hydroxypyrazolines</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The most common mutation of CFTR, affecting approximately 90% of CF patients, is a deletion of phenylalanine at position 508 (F508del, ΔF508). Misfolding of ΔF508-CFTR impairs both its trafficking to the plasma membrane and its chloride channel activity. To identify small molecules that can restore channel activity of ΔF508-CFTR, we synthesized and evaluated eighteen novel hydroxypyrazoline analogues as CFTR potentiators. To elucidate potentiation activities of hydroxypyrazolines for ΔF508-CFTR, CFTR activity was measured using a halide-sensitive YFP assay, Ussing chamber assay and patch-clamp technique. Compounds 7p, 7q and 7r exhibited excellent potentiation with EC50 value <10 μM. Among the compounds, 7q (a novel CFTR potentiator, CP7q) showed the highest potentiation activity with EC50 values of 0.88 ± 0.11 and 4.45 ± 0.31 μM for wild-type and ΔF508-CFTR, respectively. In addition, CP7q significantly potentiated chloride conductance of G551D-CFTR, a CFTR gating mutant; its maximal potentiation activity was 1.9 fold higher than the well-known CFTR potentiator genistein. Combination treatment with CP7q and VX-809, a corrector of ΔF508-CFTR, significantly enhanced functional rescue of ΔF508-CFTR compared with VX-809 alone. CP7q did not alter the cytosolic cAMP level and showed no cytotoxicity at the concentration showing maximum efficacy. The hydroxypyrazolines may be potential development candidates for drug therapy of cystic fibrosis.</description><subject>Aminopyridines - therapeutic use</subject><subject>Animals</subject><subject>Bacterial Proteins - chemistry</subject><subject>Benzodioxoles - therapeutic use</subject><subject>Biology and Life Sciences</subject><subject>Cell Line</subject><subject>Cell Line, Tumor</subject><subject>Cell Membrane - metabolism</subject><subject>Cell Proliferation</subject><subject>Channel gating</subject><subject>Chemical synthesis</subject><subject>Chloride</subject><subject>Chloride conductance</subject><subject>Chlorides</subject><subject>Chlorides - chemistry</subject><subject>Clinical trials</subject><subject>Cyclic AMP - metabolism</subject><subject>Cystic fibrosis</subject><subject>Cystic Fibrosis - drug therapy</subject><subject>Cystic Fibrosis - genetics</subject><subject>Cystic Fibrosis Transmembrane Conductance Regulator - genetics</subject><subject>Cytotoxicity</subject><subject>Defects</subject><subject>Epithelial Cells - cytology</subject><subject>Gene Deletion</subject><subject>Genistein</subject><subject>Genistein - chemistry</subject><subject>Humans</subject><subject>Kinases</subject><subject>Luminescent Proteins - chemistry</subject><subject>Medicine and Health Sciences</subject><subject>Membrane trafficking</subject><subject>Mutation</subject><subject>Nose - physiology</subject><subject>Patch-Clamp Techniques</subject><subject>Pharmaceutical sciences</subject><subject>Pharmacy</subject><subject>Phenylalanine</subject><subject>Phenylalanine - genetics</subject><subject>Physical Sciences</subject><subject>Plasma</subject><subject>Potentiation</subject><subject>Proteins</subject><subject>Pyrazoles - therapeutic use</subject><subject>Rats</subject><subject>Research and analysis methods</subject><subject>Resistance</subject><subject>Structure-Activity Relationship</subject><subject>Sulfonamides - therapeutic use</subject><subject>Toxicity</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptUttu1DAUtBAVLYU_QGCJF16y9d3OCxIKbFupLQitxKPlxE7JyhsvdlIRvoPv4pvwdtOqRTzZOmdmzpyjAeAVRgtMJT5ZhzH2xi-2oXcLhFmJKX4CjnBJSSEIok8f_A_B85TWCHGqhHgGDolQgnJKj8C3L2Fw_dCZoQs9DC3883vJkSqg6S085Rx_LKrl6mtx6WzGOAsrX8BqjDGTYD3Bq3DjPDybbAw_p-0Uza_gu96lF-CgNT65l_N7DFbLT6vqrLj4fHpefbgoGk7EUDCDuWRWMdJSaU2biyVjIlsr25ohXPKWcU4IR9hJh5sSC2VUjagkyFhCj8GbvezWh6TnkySNpWCUES55RpzvETaYtd7GbmPipIPp9G0hxGtt4tA13mkhsjpxpkYKMSeFqm2eJZtaSeUUrrPW-3naWG-cbfINovGPRB93-u67vg43mkm2c54F3s0CMfwYXRr0pkuN8970Loy3vjnGVAiZoW__gf5_O7ZHNTGkFF17bwYjvYvJHUvvYqLnmGTa64eL3JPuckH_AuqiuIw</recordid><startdate>20160210</startdate><enddate>20160210</enddate><creator>Park, Jinhong</creator><creator>Khloya, Poonam</creator><creator>Seo, Yohan</creator><creator>Kumar, Satish</creator><creator>Lee, Ho K</creator><creator>Jeon, Dong-Kyu</creator><creator>Jo, Sungwoo</creator><creator>Sharma, Pawan K</creator><creator>Namkung, Wan</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160210</creationdate><title>Potentiation of ΔF508- and G551D-CFTR-Mediated Cl- Current by Novel Hydroxypyrazolines</title><author>Park, Jinhong ; Khloya, Poonam ; Seo, Yohan ; Kumar, Satish ; Lee, Ho K ; Jeon, Dong-Kyu ; Jo, Sungwoo ; Sharma, Pawan K ; Namkung, Wan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-4a1574d842f37daf52694465339fb40195f45522501e7e1c9168a8b03720ad23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Aminopyridines - therapeutic use</topic><topic>Animals</topic><topic>Bacterial Proteins - chemistry</topic><topic>Benzodioxoles - therapeutic use</topic><topic>Biology and Life Sciences</topic><topic>Cell Line</topic><topic>Cell Line, Tumor</topic><topic>Cell Membrane - metabolism</topic><topic>Cell Proliferation</topic><topic>Channel gating</topic><topic>Chemical synthesis</topic><topic>Chloride</topic><topic>Chloride conductance</topic><topic>Chlorides</topic><topic>Chlorides - chemistry</topic><topic>Clinical trials</topic><topic>Cyclic AMP - metabolism</topic><topic>Cystic fibrosis</topic><topic>Cystic Fibrosis - drug therapy</topic><topic>Cystic Fibrosis - genetics</topic><topic>Cystic Fibrosis Transmembrane Conductance Regulator - genetics</topic><topic>Cytotoxicity</topic><topic>Defects</topic><topic>Epithelial Cells - cytology</topic><topic>Gene Deletion</topic><topic>Genistein</topic><topic>Genistein - chemistry</topic><topic>Humans</topic><topic>Kinases</topic><topic>Luminescent Proteins - chemistry</topic><topic>Medicine and Health Sciences</topic><topic>Membrane trafficking</topic><topic>Mutation</topic><topic>Nose - physiology</topic><topic>Patch-Clamp Techniques</topic><topic>Pharmaceutical sciences</topic><topic>Pharmacy</topic><topic>Phenylalanine</topic><topic>Phenylalanine - genetics</topic><topic>Physical Sciences</topic><topic>Plasma</topic><topic>Potentiation</topic><topic>Proteins</topic><topic>Pyrazoles - therapeutic use</topic><topic>Rats</topic><topic>Research and analysis methods</topic><topic>Resistance</topic><topic>Structure-Activity Relationship</topic><topic>Sulfonamides - therapeutic use</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Jinhong</creatorcontrib><creatorcontrib>Khloya, Poonam</creatorcontrib><creatorcontrib>Seo, Yohan</creatorcontrib><creatorcontrib>Kumar, Satish</creatorcontrib><creatorcontrib>Lee, Ho K</creatorcontrib><creatorcontrib>Jeon, Dong-Kyu</creatorcontrib><creatorcontrib>Jo, Sungwoo</creatorcontrib><creatorcontrib>Sharma, Pawan K</creatorcontrib><creatorcontrib>Namkung, Wan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Jinhong</au><au>Khloya, Poonam</au><au>Seo, Yohan</au><au>Kumar, Satish</au><au>Lee, Ho K</au><au>Jeon, Dong-Kyu</au><au>Jo, Sungwoo</au><au>Sharma, Pawan K</au><au>Namkung, Wan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Potentiation of ΔF508- and G551D-CFTR-Mediated Cl- Current by Novel Hydroxypyrazolines</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-02-10</date><risdate>2016</risdate><volume>11</volume><issue>2</issue><spage>e0149131</spage><epage>e0149131</epage><pages>e0149131-e0149131</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The most common mutation of CFTR, affecting approximately 90% of CF patients, is a deletion of phenylalanine at position 508 (F508del, ΔF508). Misfolding of ΔF508-CFTR impairs both its trafficking to the plasma membrane and its chloride channel activity. To identify small molecules that can restore channel activity of ΔF508-CFTR, we synthesized and evaluated eighteen novel hydroxypyrazoline analogues as CFTR potentiators. To elucidate potentiation activities of hydroxypyrazolines for ΔF508-CFTR, CFTR activity was measured using a halide-sensitive YFP assay, Ussing chamber assay and patch-clamp technique. Compounds 7p, 7q and 7r exhibited excellent potentiation with EC50 value <10 μM. Among the compounds, 7q (a novel CFTR potentiator, CP7q) showed the highest potentiation activity with EC50 values of 0.88 ± 0.11 and 4.45 ± 0.31 μM for wild-type and ΔF508-CFTR, respectively. In addition, CP7q significantly potentiated chloride conductance of G551D-CFTR, a CFTR gating mutant; its maximal potentiation activity was 1.9 fold higher than the well-known CFTR potentiator genistein. Combination treatment with CP7q and VX-809, a corrector of ΔF508-CFTR, significantly enhanced functional rescue of ΔF508-CFTR compared with VX-809 alone. CP7q did not alter the cytosolic cAMP level and showed no cytotoxicity at the concentration showing maximum efficacy. The hydroxypyrazolines may be potential development candidates for drug therapy of cystic fibrosis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26863533</pmid><doi>10.1371/journal.pone.0149131</doi><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2016-02, Vol.11 (2), p.e0149131-e0149131 |
| issn | 1932-6203 1932-6203 |
| language | eng |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Aminopyridines - therapeutic use Animals Bacterial Proteins - chemistry Benzodioxoles - therapeutic use Biology and Life Sciences Cell Line Cell Line, Tumor Cell Membrane - metabolism Cell Proliferation Channel gating Chemical synthesis Chloride Chloride conductance Chlorides Chlorides - chemistry Clinical trials Cyclic AMP - metabolism Cystic fibrosis Cystic Fibrosis - drug therapy Cystic Fibrosis - genetics Cystic Fibrosis Transmembrane Conductance Regulator - genetics Cytotoxicity Defects Epithelial Cells - cytology Gene Deletion Genistein Genistein - chemistry Humans Kinases Luminescent Proteins - chemistry Medicine and Health Sciences Membrane trafficking Mutation Nose - physiology Patch-Clamp Techniques Pharmaceutical sciences Pharmacy Phenylalanine Phenylalanine - genetics Physical Sciences Plasma Potentiation Proteins Pyrazoles - therapeutic use Rats Research and analysis methods Resistance Structure-Activity Relationship Sulfonamides - therapeutic use Toxicity |
| title | Potentiation of ΔF508- and G551D-CFTR-Mediated Cl- Current by Novel Hydroxypyrazolines |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T08%3A04%3A15IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Potentiation%20of%20%CE%94F508-%20and%20G551D-CFTR-Mediated%20Cl-%20Current%20by%20Novel%20Hydroxypyrazolines&rft.jtitle=PloS%20one&rft.au=Park,%20Jinhong&rft.date=2016-02-10&rft.volume=11&rft.issue=2&rft.spage=e0149131&rft.epage=e0149131&rft.pages=e0149131-e0149131&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0149131&rft_dat=%3Cproquest_plos_%3E1765113667%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1764342575&rft_id=info:pmid/26863533&rft_doaj_id=oai_doaj_org_article_661682eab0804e768bda8b7cb878e81b&rfr_iscdi=true |