LymphedemaV1, Main, Exploration, bibRecord, 001893

Repurposing Auranofin as a Lead Candidate for Treatment of Lymphatic Filariasis and Onchocerciasis

Identifieur interne : 001893 ( Main/Exploration ); précédent : 001892; suivant : 001894

Repurposing Auranofin as a Lead Candidate for Treatment of Lymphatic Filariasis and Onchocerciasis

Auteurs : Christina A. Bulman [États-Unis] ; Chelsea M. Bidlow [États-Unis] ; Sara Lustigman [États-Unis] ; Fidelis Cho-Ngwa [Cameroun] ; David Williams [États-Unis] ; Alberto A. Rasc N Jr [États-Unis] ; Nancy Tricoche [États-Unis] ; Moses Samje [Cameroun] ; Aaron Bell [États-Unis] ; Brian Suzuki [États-Unis] ; K. C. Lim [États-Unis] ; Nonglak Supakorndej [États-Unis] ; Prasit Supakorndej [États-Unis] ; Alan R. Wolfe [États-Unis] ; Giselle M. Knudsen [États-Unis] ; Steven Chen [États-Unis] ; Chris Wilson [États-Unis] ; Kean-Hooi Ang [États-Unis] ; Michelle Arkin [États-Unis] ; Jiri Gut [États-Unis] ; Chris Franklin [États-Unis] ; Chris Marcellino [États-Unis] ; James H. Mckerrow [États-Unis] ; Anjan Debnath [États-Unis] ; Judy A. Sakanari [États-Unis]

Source :

PLoS Neglected Tropical Diseases [ 1935-2727 ] ; 2015.

RBID : PMC:4336141

Descripteurs français

KwdFr :
- Adulte, Albendazole (usage thérapeutique), Animaux, Antihelminthiques (usage thérapeutique), Auranofine (usage thérapeutique), Bovins, Brugia malayi (), Diéthylcarbamazine (usage thérapeutique), Femelle, Filaricides (usage thérapeutique), Filariose lymphatique (parasitologie), Filariose lymphatique (traitement médicamenteux), Gerbillinae, Haplorhini, Humains, Ivermectine (usage thérapeutique), Lignée cellulaire, Loa (), Loase (parasitologie), Loase (traitement médicamenteux), Microfilaria (), Onchocerca volvulus (), Onchocercose (parasitologie), Onchocercose (traitement médicamenteux), Repositionnement des médicaments.
MESH :
- parasitologie : Filariose lymphatique, Loase, Onchocercose.
- traitement médicamenteux : Filariose lymphatique, Loase, Onchocercose.
- usage thérapeutique : Albendazole, Antihelminthiques, Auranofine, Diéthylcarbamazine, Filaricides, Ivermectine.
- Adulte, Animaux, Bovins, Brugia malayi, Femelle, Gerbillinae, Haplorhini, Humains, Lignée cellulaire, Loa, Microfilaria, Onchocerca volvulus, Repositionnement des médicaments.

English descriptors

KwdEn :
- Adult, Albendazole (therapeutic use), Animals, Anthelmintics (therapeutic use), Auranofin (therapeutic use), Brugia malayi (drug effects), Cattle, Cell Line, Diethylcarbamazine (therapeutic use), Drug Repositioning, Elephantiasis, Filarial (drug therapy), Elephantiasis, Filarial (parasitology), Female, Filaricides (therapeutic use), Gerbillinae, Haplorhini, Humans, Ivermectin (therapeutic use), Loa (drug effects), Loiasis (drug therapy), Loiasis (parasitology), Microfilariae (drug effects), Onchocerca volvulus (drug effects), Onchocerciasis (drug therapy), Onchocerciasis (parasitology).
MESH :
- chemical , therapeutic use : Albendazole, Anthelmintics, Auranofin, Diethylcarbamazine, Filaricides, Ivermectin.
- drug effects : Brugia malayi, Loa, Microfilariae, Onchocerca volvulus.
- drug therapy : Elephantiasis, Filarial, Loiasis, Onchocerciasis.
- parasitology : Elephantiasis, Filarial, Loiasis, Onchocerciasis.
- Adult, Animals, Cattle, Cell Line, Drug Repositioning, Female, Gerbillinae, Haplorhini, Humans.

Abstract

Two major human diseases caused by filariid nematodes are onchocerciasis, or river blindness, and lymphatic filariasis, which can lead to elephantiasis. The drugs ivermectin, diethylcarbamazine (DEC), and albendazole are used in control programs for these diseases, but are mainly effective against the microfilarial stage and have minimal or no effect on adult worms. Adult Onchocerca volvulus and Brugia malayi worms (macrofilariae) can live for up to 15 years, reproducing and allowing the infection to persist in a population. Therefore, to support control or elimination of these two diseases, effective macrofilaricidal drugs are necessary, in addition to current drugs. In an effort to identify macrofilaricidal drugs, we screened an FDA-approved library with adult worms of Brugia spp. and Onchocerca ochengi, third-stage larvae (L3s) of Onchocerca volvulus, and the microfilariae of both O. ochengi and Loa loa. We found that auranofin, a gold-containing drug used for rheumatoid arthritis, was effective in vitro in killing both Brugia spp. and O. ochengi adult worms and in inhibiting the molting of L3s of O. volvulus with IC₅₀ values in the low micromolar to nanomolar range. Auranofin had an approximately 43-fold higher IC₅₀ against the microfilariae of L. loa compared with the IC₅₀ for adult female O. ochengi, which may be beneficial if used in areas where Onchocerca and Brugia are co-endemic with L. loa, to prevent severe adverse reactions to the drug-induced death of L. loa microfilariae. Further testing indicated that auranofin is also effective in reducing Brugia adult worm burden in infected gerbils and that auranofin may be targeting the thioredoxin reductase in this nematode.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336141

DOI: 10.1371/journal.pntd.0003534
PubMed: 25700363
PubMed Central: 4336141

Affiliations:

Le document en format XML

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<author><name sortKey="Ang, Kean Hooi" sort="Ang, Kean Hooi" uniqKey="Ang K" first="Kean-Hooi" last="Ang">Kean-Hooi Ang</name>
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<author><name sortKey="Arkin, Michelle" sort="Arkin, Michelle" uniqKey="Arkin M" first="Michelle" last="Arkin">Michelle Arkin</name>
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<author><name sortKey="Franklin, Chris" sort="Franklin, Chris" uniqKey="Franklin C" first="Chris" last="Franklin">Chris Franklin</name>
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<placeName><region type="state">Ohio</region>
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<wicri:regionArea>Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, California</wicri:regionArea>
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<author><name sortKey="Debnath, Anjan" sort="Debnath, Anjan" uniqKey="Debnath A" first="Anjan" last="Debnath">Anjan Debnath</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Repurposing Auranofin as a Lead Candidate for Treatment of Lymphatic Filariasis and Onchocerciasis</title>
<author><name sortKey="Bulman, Christina A" sort="Bulman, Christina A" uniqKey="Bulman C" first="Christina A." last="Bulman">Christina A. Bulman</name>
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<author><name sortKey="Bidlow, Chelsea M" sort="Bidlow, Chelsea M" uniqKey="Bidlow C" first="Chelsea M." last="Bidlow">Chelsea M. Bidlow</name>
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</affiliation>
</author>
<author><name sortKey="Lustigman, Sara" sort="Lustigman, Sara" uniqKey="Lustigman S" first="Sara" last="Lustigman">Sara Lustigman</name>
<affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Cho Ngwa, Fidelis" sort="Cho Ngwa, Fidelis" uniqKey="Cho Ngwa F" first="Fidelis" last="Cho-Ngwa">Fidelis Cho-Ngwa</name>
<affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Department of Biochemistry and Molecular Biology, University of Buea, Buea, SW Region, Cameroon</addr-line>
</nlm:aff>
<country xml:lang="fr">Cameroun</country>
<wicri:regionArea>Department of Biochemistry and Molecular Biology, University of Buea, Buea, SW Region</wicri:regionArea>
<wicri:noRegion>SW Region</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Williams, David" sort="Williams, David" uniqKey="Williams D" first="David" last="Williams">David Williams</name>
<affiliation wicri:level="2"><nlm:aff id="aff004"><addr-line>Department of Immunology and Microbiology, Rush University Medical Center, Chicago, Illinois, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Immunology and Microbiology, Rush University Medical Center, Chicago, Illinois</wicri:regionArea>
<placeName><region type="state">Illinois</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Rasc N Jr, Alberto A" sort="Rasc N Jr, Alberto A" uniqKey="Rasc N Jr A" first="Alberto A." last="Rasc N Jr">Alberto A. Rasc N Jr</name>
<affiliation wicri:level="2"><nlm:aff id="aff001"><addr-line>Center for Discovery and Innovation in Parasitic Diseases, University of California San Francisco, San Francisco, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Discovery and Innovation in Parasitic Diseases, University of California San Francisco, San Francisco, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="aff005"><addr-line>Department of Chemistry, San Jose State University, San Jose, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Chemistry, San Jose State University, San Jose, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tricoche, Nancy" sort="Tricoche, Nancy" uniqKey="Tricoche N" first="Nancy" last="Tricoche">Nancy Tricoche</name>
<affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Samje, Moses" sort="Samje, Moses" uniqKey="Samje M" first="Moses" last="Samje">Moses Samje</name>
<affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Department of Biochemistry and Molecular Biology, University of Buea, Buea, SW Region, Cameroon</addr-line>
</nlm:aff>
<country xml:lang="fr">Cameroun</country>
<wicri:regionArea>Department of Biochemistry and Molecular Biology, University of Buea, Buea, SW Region</wicri:regionArea>
<wicri:noRegion>SW Region</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Bell, Aaron" sort="Bell, Aaron" uniqKey="Bell A" first="Aaron" last="Bell">Aaron Bell</name>
<affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Suzuki, Brian" sort="Suzuki, Brian" uniqKey="Suzuki B" first="Brian" last="Suzuki">Brian Suzuki</name>
<affiliation wicri:level="2"><nlm:aff id="aff001"><addr-line>Center for Discovery and Innovation in Parasitic Diseases, University of California San Francisco, San Francisco, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Discovery and Innovation in Parasitic Diseases, University of California San Francisco, San Francisco, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lim, K C" sort="Lim, K C" uniqKey="Lim K" first="K. C." last="Lim">K. C. Lim</name>
<affiliation wicri:level="2"><nlm:aff id="aff001"><addr-line>Center for Discovery and Innovation in Parasitic Diseases, University of California San Francisco, San Francisco, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Discovery and Innovation in Parasitic Diseases, University of California San Francisco, San Francisco, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Supakorndej, Nonglak" sort="Supakorndej, Nonglak" uniqKey="Supakorndej N" first="Nonglak" last="Supakorndej">Nonglak Supakorndej</name>
<affiliation wicri:level="2"><nlm:aff id="aff006"><addr-line>FilariaTech, Athens, Georgia, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>FilariaTech, Athens, Georgia</wicri:regionArea>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Supakorndej, Prasit" sort="Supakorndej, Prasit" uniqKey="Supakorndej P" first="Prasit" last="Supakorndej">Prasit Supakorndej</name>
<affiliation wicri:level="2"><nlm:aff id="aff007"><addr-line>Department of Infectious Diseases, University of Georgia, Athens, Georgia, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Infectious Diseases, University of Georgia, Athens, Georgia</wicri:regionArea>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wolfe, Alan R" sort="Wolfe, Alan R" uniqKey="Wolfe A" first="Alan R." last="Wolfe">Alan R. Wolfe</name>
<affiliation wicri:level="2"><nlm:aff id="aff008"><addr-line>Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Knudsen, Giselle M" sort="Knudsen, Giselle M" uniqKey="Knudsen G" first="Giselle M." last="Knudsen">Giselle M. Knudsen</name>
<affiliation wicri:level="2"><nlm:aff id="aff009"><addr-line>UCSF Mass Spectrometry Facility, Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>UCSF Mass Spectrometry Facility, Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Chen, Steven" sort="Chen, Steven" uniqKey="Chen S" first="Steven" last="Chen">Steven Chen</name>
<affiliation wicri:level="2"><nlm:aff id="aff010"><addr-line>Small Molecule Discovery Center, University of California San Francisco, San Francisco, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Small Molecule Discovery Center, University of California San Francisco, San Francisco, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wilson, Chris" sort="Wilson, Chris" uniqKey="Wilson C" first="Chris" last="Wilson">Chris Wilson</name>
<affiliation wicri:level="2"><nlm:aff id="aff010"><addr-line>Small Molecule Discovery Center, University of California San Francisco, San Francisco, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Small Molecule Discovery Center, University of California San Francisco, San Francisco, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ang, Kean Hooi" sort="Ang, Kean Hooi" uniqKey="Ang K" first="Kean-Hooi" last="Ang">Kean-Hooi Ang</name>
<affiliation wicri:level="2"><nlm:aff id="aff010"><addr-line>Small Molecule Discovery Center, University of California San Francisco, San Francisco, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Small Molecule Discovery Center, University of California San Francisco, San Francisco, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Arkin, Michelle" sort="Arkin, Michelle" uniqKey="Arkin M" first="Michelle" last="Arkin">Michelle Arkin</name>
<affiliation wicri:level="2"><nlm:aff id="aff010"><addr-line>Small Molecule Discovery Center, University of California San Francisco, San Francisco, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Small Molecule Discovery Center, University of California San Francisco, San Francisco, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gut, Jiri" sort="Gut, Jiri" uniqKey="Gut J" first="Jiri" last="Gut">Jiri Gut</name>
<affiliation wicri:level="2"><nlm:aff id="aff001"><addr-line>Center for Discovery and Innovation in Parasitic Diseases, University of California San Francisco, San Francisco, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Discovery and Innovation in Parasitic Diseases, University of California San Francisco, San Francisco, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Franklin, Chris" sort="Franklin, Chris" uniqKey="Franklin C" first="Chris" last="Franklin">Chris Franklin</name>
<affiliation wicri:level="2"><nlm:aff id="aff001"><addr-line>Center for Discovery and Innovation in Parasitic Diseases, University of California San Francisco, San Francisco, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Discovery and Innovation in Parasitic Diseases, University of California San Francisco, San Francisco, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Marcellino, Chris" sort="Marcellino, Chris" uniqKey="Marcellino C" first="Chris" last="Marcellino">Chris Marcellino</name>
<affiliation wicri:level="2"><nlm:aff id="aff011"><addr-line>Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Case Western Reserve University School of Medicine, Cleveland, Ohio</wicri:regionArea>
<placeName><region type="state">Ohio</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mckerrow, James H" sort="Mckerrow, James H" uniqKey="Mckerrow J" first="James H." last="Mckerrow">James H. Mckerrow</name>
<affiliation wicri:level="2"><nlm:aff id="aff012"><addr-line>Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Debnath, Anjan" sort="Debnath, Anjan" uniqKey="Debnath A" first="Anjan" last="Debnath">Anjan Debnath</name>
<affiliation wicri:level="2"><nlm:aff id="aff012"><addr-line>Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Sakanari, Judy A" sort="Sakanari, Judy A" uniqKey="Sakanari J" first="Judy A." last="Sakanari">Judy A. Sakanari</name>
<affiliation wicri:level="2"><nlm:aff id="aff001"><addr-line>Center for Discovery and Innovation in Parasitic Diseases, University of California San Francisco, San Francisco, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Discovery and Innovation in Parasitic Diseases, University of California San Francisco, San Francisco, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">PLoS Neglected Tropical Diseases</title>
<idno type="ISSN">1935-2727</idno>
<idno type="eISSN">1935-2735</idno>
<imprint><date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term>
<term>Albendazole (therapeutic use)</term>
<term>Animals</term>
<term>Anthelmintics (therapeutic use)</term>
<term>Auranofin (therapeutic use)</term>
<term>Brugia malayi (drug effects)</term>
<term>Cattle</term>
<term>Cell Line</term>
<term>Diethylcarbamazine (therapeutic use)</term>
<term>Drug Repositioning</term>
<term>Elephantiasis, Filarial (drug therapy)</term>
<term>Elephantiasis, Filarial (parasitology)</term>
<term>Female</term>
<term>Filaricides (therapeutic use)</term>
<term>Gerbillinae</term>
<term>Haplorhini</term>
<term>Humans</term>
<term>Ivermectin (therapeutic use)</term>
<term>Loa (drug effects)</term>
<term>Loiasis (drug therapy)</term>
<term>Loiasis (parasitology)</term>
<term>Microfilariae (drug effects)</term>
<term>Onchocerca volvulus (drug effects)</term>
<term>Onchocerciasis (drug therapy)</term>
<term>Onchocerciasis (parasitology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term>
<term>Albendazole (usage thérapeutique)</term>
<term>Animaux</term>
<term>Antihelminthiques (usage thérapeutique)</term>
<term>Auranofine (usage thérapeutique)</term>
<term>Bovins</term>
<term>Brugia malayi ()</term>
<term>Diéthylcarbamazine (usage thérapeutique)</term>
<term>Femelle</term>
<term>Filaricides (usage thérapeutique)</term>
<term>Filariose lymphatique (parasitologie)</term>
<term>Filariose lymphatique (traitement médicamenteux)</term>
<term>Gerbillinae</term>
<term>Haplorhini</term>
<term>Humains</term>
<term>Ivermectine (usage thérapeutique)</term>
<term>Lignée cellulaire</term>
<term>Loa ()</term>
<term>Loase (parasitologie)</term>
<term>Loase (traitement médicamenteux)</term>
<term>Microfilaria ()</term>
<term>Onchocerca volvulus ()</term>
<term>Onchocercose (parasitologie)</term>
<term>Onchocercose (traitement médicamenteux)</term>
<term>Repositionnement des médicaments</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Albendazole</term>
<term>Anthelmintics</term>
<term>Auranofin</term>
<term>Diethylcarbamazine</term>
<term>Filaricides</term>
<term>Ivermectin</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Brugia malayi</term>
<term>Loa</term>
<term>Microfilariae</term>
<term>Onchocerca volvulus</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Elephantiasis, Filarial</term>
<term>Loiasis</term>
<term>Onchocerciasis</term>
</keywords>
<keywords scheme="MESH" qualifier="parasitologie" xml:lang="fr"><term>Filariose lymphatique</term>
<term>Loase</term>
<term>Onchocercose</term>
</keywords>
<keywords scheme="MESH" qualifier="parasitology" xml:lang="en"><term>Elephantiasis, Filarial</term>
<term>Loiasis</term>
<term>Onchocerciasis</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Filariose lymphatique</term>
<term>Loase</term>
<term>Onchocercose</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Albendazole</term>
<term>Antihelminthiques</term>
<term>Auranofine</term>
<term>Diéthylcarbamazine</term>
<term>Filaricides</term>
<term>Ivermectine</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Animals</term>
<term>Cattle</term>
<term>Cell Line</term>
<term>Drug Repositioning</term>
<term>Female</term>
<term>Gerbillinae</term>
<term>Haplorhini</term>
<term>Humans</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adulte</term>
<term>Animaux</term>
<term>Bovins</term>
<term>Brugia malayi</term>
<term>Femelle</term>
<term>Gerbillinae</term>
<term>Haplorhini</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Loa</term>
<term>Microfilaria</term>
<term>Onchocerca volvulus</term>
<term>Repositionnement des médicaments</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Two major human diseases caused by filariid nematodes are onchocerciasis, or river blindness, and lymphatic filariasis, which can lead to elephantiasis. The drugs ivermectin, diethylcarbamazine (DEC), and albendazole are used in control programs for these diseases, but are mainly effective against the microfilarial stage and have minimal or no effect on adult worms. Adult <italic>Onchocerca volvulus</italic>
 and <italic>Brugia malayi</italic>
 worms (macrofilariae) can live for up to 15 years, reproducing and allowing the infection to persist in a population. Therefore, to support control or elimination of these two diseases, effective macrofilaricidal drugs are necessary, in addition to current drugs. In an effort to identify macrofilaricidal drugs, we screened an FDA-approved library with adult worms of <italic>Brugia</italic>
 spp. and <italic>Onchocerca ochengi</italic>
, third-stage larvae (L3s) of <italic>Onchocerca volvulus</italic>
, and the microfilariae of both <italic>O. ochengi</italic>
 and <italic>Loa loa</italic>
. We found that auranofin, a gold-containing drug used for rheumatoid arthritis, was effective <italic>in vitro</italic>
 in killing both <italic>Brugia</italic>
 spp. and <italic>O. ochengi</italic>
 adult worms and in inhibiting the molting of L3s of <italic>O. volvulus</italic>
 with IC<sub>50</sub>
 values in the low micromolar to nanomolar range. Auranofin had an approximately 43-fold higher IC<sub>50</sub>
 against the microfilariae of <italic>L. loa</italic>
 compared with the IC<sub>50</sub>
 for adult female <italic>O. ochengi</italic>
, which may be beneficial if used in areas where <italic>Onchocerca</italic>
 and <italic>Brugia</italic>
 are co-endemic with <italic>L. loa</italic>
, to prevent severe adverse reactions to the drug-induced death of <italic>L. loa</italic>
 microfilariae. Further testing indicated that auranofin is also effective in reducing <italic>Brugia</italic>
 adult worm burden in infected gerbils and that auranofin may be targeting the thioredoxin reductase in this nematode.</p>
</div>
</front>
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<name sortKey="Knudsen, Giselle M" sort="Knudsen, Giselle M" uniqKey="Knudsen G" first="Giselle M." last="Knudsen">Giselle M. Knudsen</name>
<name sortKey="Lim, K C" sort="Lim, K C" uniqKey="Lim K" first="K. C." last="Lim">K. C. Lim</name>
<name sortKey="Lustigman, Sara" sort="Lustigman, Sara" uniqKey="Lustigman S" first="Sara" last="Lustigman">Sara Lustigman</name>
<name sortKey="Marcellino, Chris" sort="Marcellino, Chris" uniqKey="Marcellino C" first="Chris" last="Marcellino">Chris Marcellino</name>
<name sortKey="Mckerrow, James H" sort="Mckerrow, James H" uniqKey="Mckerrow J" first="James H." last="Mckerrow">James H. Mckerrow</name>
<name sortKey="Rasc N Jr, Alberto A" sort="Rasc N Jr, Alberto A" uniqKey="Rasc N Jr A" first="Alberto A." last="Rasc N Jr">Alberto A. Rasc N Jr</name>
<name sortKey="Rasc N Jr, Alberto A" sort="Rasc N Jr, Alberto A" uniqKey="Rasc N Jr A" first="Alberto A." last="Rasc N Jr">Alberto A. Rasc N Jr</name>
<name sortKey="Sakanari, Judy A" sort="Sakanari, Judy A" uniqKey="Sakanari J" first="Judy A." last="Sakanari">Judy A. Sakanari</name>
<name sortKey="Supakorndej, Nonglak" sort="Supakorndej, Nonglak" uniqKey="Supakorndej N" first="Nonglak" last="Supakorndej">Nonglak Supakorndej</name>
<name sortKey="Supakorndej, Prasit" sort="Supakorndej, Prasit" uniqKey="Supakorndej P" first="Prasit" last="Supakorndej">Prasit Supakorndej</name>
<name sortKey="Suzuki, Brian" sort="Suzuki, Brian" uniqKey="Suzuki B" first="Brian" last="Suzuki">Brian Suzuki</name>
<name sortKey="Tricoche, Nancy" sort="Tricoche, Nancy" uniqKey="Tricoche N" first="Nancy" last="Tricoche">Nancy Tricoche</name>
<name sortKey="Williams, David" sort="Williams, David" uniqKey="Williams D" first="David" last="Williams">David Williams</name>
<name sortKey="Wilson, Chris" sort="Wilson, Chris" uniqKey="Wilson C" first="Chris" last="Wilson">Chris Wilson</name>
<name sortKey="Wolfe, Alan R" sort="Wolfe, Alan R" uniqKey="Wolfe A" first="Alan R." last="Wolfe">Alan R. Wolfe</name>
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<country name="Cameroun"><noRegion><name sortKey="Cho Ngwa, Fidelis" sort="Cho Ngwa, Fidelis" uniqKey="Cho Ngwa F" first="Fidelis" last="Cho-Ngwa">Fidelis Cho-Ngwa</name>
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<name sortKey="Samje, Moses" sort="Samje, Moses" uniqKey="Samje M" first="Moses" last="Samje">Moses Samje</name>
</country>
</tree>
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</record>

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HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001893 | SxmlIndent | more

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{{Explor lien
   |wiki=    Wicri/Sante
   |area=    LymphedemaV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     PMC:4336141
   |texte=   Repurposing Auranofin as a Lead Candidate for Treatment of Lymphatic Filariasis and Onchocerciasis
}}

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This area was generated with Dilib version V0.6.31.
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Serveur d'exploration sur le lymphœdème

Repurposing Auranofin as a Lead Candidate for Treatment of Lymphatic Filariasis and Onchocerciasis

Repurposing Auranofin as a Lead Candidate for Treatment of Lymphatic Filariasis and Onchocerciasis

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	Serveur d'exploration sur le lymphœdème
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