Antimalarial Activity of KAF156 in Falciparum and Vivax Malaria
With the emergence and spread of artemisinin resistance, new therapies for malaria are needed. This study shows that the imidazolopiperazine KAF156, a new antimalarial compound, has in vivo antimalarial activity. Expanding artemisinin resistance and worsening partner-drug resistance in Southeast Asi...
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| Veröffentlicht in: | The New England journal of medicine 2016-09, Vol.375 (12), p.1152-1160 |
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| creator | White, Nicholas J Duong, Tran T Uthaisin, Chirapong Nosten, François Phyo, Aung P Hanboonkunupakarn, Borimas Pukrittayakamee, Sasithon Jittamala, Podjanee Chuthasmit, Kittiphum Cheung, Ming S Feng, Yiyan Li, Ruobing Magnusson, Baldur Sultan, Marc Wieser, Daniela Xun, Xiaolei Zhao, Rong Diagana, Thierry T Pertel, Peter Leong, F. Joel |
| description | With the emergence and spread of artemisinin resistance, new therapies for malaria are needed. This study shows that the imidazolopiperazine KAF156, a new antimalarial compound, has in vivo antimalarial activity.
Expanding artemisinin resistance and worsening partner-drug resistance in Southeast Asia threaten the global control of
Plasmodium falciparum
malaria.
1
–
5
New drugs are needed. KAF156 represents a new class of antimalarial agents (imidazolopiperazines)
6
identified by high-throughput phenotypic screening. KAF156 has potent in vitro activity against both asexual and sexual blood stages and the preerythrocytic liver stages of the malarial parasite.
7
The mechanism of antimalarial action is unknown, but drug resistance, mediated by mutations in the
P. falciparum
cyclic amine resistance locus (
PfCARL
) gene, which encodes a protein of unknown function, can be selected.
7
In a study of 70 healthy . . . |
| doi_str_mv | 10.1056/NEJMoa1602250 |
| format | Article |
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Expanding artemisinin resistance and worsening partner-drug resistance in Southeast Asia threaten the global control of
Plasmodium falciparum
malaria.
1
–
5
New drugs are needed. KAF156 represents a new class of antimalarial agents (imidazolopiperazines)
6
identified by high-throughput phenotypic screening. KAF156 has potent in vitro activity against both asexual and sexual blood stages and the preerythrocytic liver stages of the malarial parasite.
7
The mechanism of antimalarial action is unknown, but drug resistance, mediated by mutations in the
P. falciparum
cyclic amine resistance locus (
PfCARL
) gene, which encodes a protein of unknown function, can be selected.
7
In a study of 70 healthy . . .</description><identifier>ISSN: 0028-4793</identifier><identifier>EISSN: 1533-4406</identifier><identifier>DOI: 10.1056/NEJMoa1602250</identifier><identifier>PMID: 27653565</identifier><language>eng</language><publisher>United States: Massachusetts Medical Society</publisher><subject>Administration, Oral ; Adult ; Antimalarial activity ; Antimalarial agents ; Antimalarials - administration & dosage ; Antimalarials - adverse effects ; Antimalarials - pharmacokinetics ; Antiparasitic agents ; Bradycardia ; Clinical trials ; Drug therapy ; Female ; Fever ; Humans ; Hyperbilirubinemia ; Hypokalemia ; Imidazoles - administration & dosage ; Imidazoles - adverse effects ; Imidazoles - pharmacokinetics ; Liver ; Malaria ; Malaria, Falciparum - drug therapy ; Malaria, Vivax - drug therapy ; Male ; Middle Aged ; Parasite Load ; Parasites ; Patients ; Piperazines - administration & dosage ; Piperazines - adverse effects ; Piperazines - pharmacokinetics ; Plasmodium falciparum - isolation & purification ; Plasmodium vivax - isolation & purification ; Thrombocytopenia ; Vomiting ; Young Adult</subject><ispartof>The New England journal of medicine, 2016-09, Vol.375 (12), p.1152-1160</ispartof><rights>Copyright © 2016 Massachusetts Medical Society. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c511t-a0122aff1b354ae701890cfff04e3a5073b37f77626f80069e4c88f78948c4f43</citedby><cites>FETCH-LOGICAL-c511t-a0122aff1b354ae701890cfff04e3a5073b37f77626f80069e4c88f78948c4f43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.nejm.org/doi/pdf/10.1056/NEJMoa1602250$$EPDF$$P50$$Gmms$$H</linktopdf><linktohtml>$$Uhttps://www.nejm.org/doi/full/10.1056/NEJMoa1602250$$EHTML$$P50$$Gmms$$H</linktohtml><link.rule.ids>230,314,776,780,881,2746,2747,26080,27901,27902,52357,54039</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27653565$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>White, Nicholas J</creatorcontrib><creatorcontrib>Duong, Tran T</creatorcontrib><creatorcontrib>Uthaisin, Chirapong</creatorcontrib><creatorcontrib>Nosten, François</creatorcontrib><creatorcontrib>Phyo, Aung P</creatorcontrib><creatorcontrib>Hanboonkunupakarn, Borimas</creatorcontrib><creatorcontrib>Pukrittayakamee, Sasithon</creatorcontrib><creatorcontrib>Jittamala, Podjanee</creatorcontrib><creatorcontrib>Chuthasmit, Kittiphum</creatorcontrib><creatorcontrib>Cheung, Ming S</creatorcontrib><creatorcontrib>Feng, Yiyan</creatorcontrib><creatorcontrib>Li, Ruobing</creatorcontrib><creatorcontrib>Magnusson, Baldur</creatorcontrib><creatorcontrib>Sultan, Marc</creatorcontrib><creatorcontrib>Wieser, Daniela</creatorcontrib><creatorcontrib>Xun, Xiaolei</creatorcontrib><creatorcontrib>Zhao, Rong</creatorcontrib><creatorcontrib>Diagana, Thierry T</creatorcontrib><creatorcontrib>Pertel, Peter</creatorcontrib><creatorcontrib>Leong, F. Joel</creatorcontrib><title>Antimalarial Activity of KAF156 in Falciparum and Vivax Malaria</title><title>The New England journal of medicine</title><addtitle>N Engl J Med</addtitle><description>With the emergence and spread of artemisinin resistance, new therapies for malaria are needed. This study shows that the imidazolopiperazine KAF156, a new antimalarial compound, has in vivo antimalarial activity.
Expanding artemisinin resistance and worsening partner-drug resistance in Southeast Asia threaten the global control of
Plasmodium falciparum
malaria.
1
–
5
New drugs are needed. KAF156 represents a new class of antimalarial agents (imidazolopiperazines)
6
identified by high-throughput phenotypic screening. KAF156 has potent in vitro activity against both asexual and sexual blood stages and the preerythrocytic liver stages of the malarial parasite.
7
The mechanism of antimalarial action is unknown, but drug resistance, mediated by mutations in the
P. falciparum
cyclic amine resistance locus (
PfCARL
) gene, which encodes a protein of unknown function, can be selected.
7
In a study of 70 healthy . . .</description><subject>Administration, Oral</subject><subject>Adult</subject><subject>Antimalarial activity</subject><subject>Antimalarial agents</subject><subject>Antimalarials - administration & dosage</subject><subject>Antimalarials - adverse effects</subject><subject>Antimalarials - pharmacokinetics</subject><subject>Antiparasitic agents</subject><subject>Bradycardia</subject><subject>Clinical trials</subject><subject>Drug therapy</subject><subject>Female</subject><subject>Fever</subject><subject>Humans</subject><subject>Hyperbilirubinemia</subject><subject>Hypokalemia</subject><subject>Imidazoles - administration & dosage</subject><subject>Imidazoles - adverse effects</subject><subject>Imidazoles - pharmacokinetics</subject><subject>Liver</subject><subject>Malaria</subject><subject>Malaria, Falciparum - drug therapy</subject><subject>Malaria, Vivax - drug therapy</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Parasite Load</subject><subject>Parasites</subject><subject>Patients</subject><subject>Piperazines - administration & dosage</subject><subject>Piperazines - adverse effects</subject><subject>Piperazines - pharmacokinetics</subject><subject>Plasmodium falciparum - isolation & purification</subject><subject>Plasmodium vivax - isolation & purification</subject><subject>Thrombocytopenia</subject><subject>Vomiting</subject><subject>Young Adult</subject><issn>0028-4793</issn><issn>1533-4406</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp1kDtPwzAURi0EoqUwsqJIiDHgt5MFFFUtrxYWYLVc1wZXeRQnqei_xyilogNe7uBzz_30AXCK4CWCjF89jR6mlUIcYszgHugjRkhMKeT7oA8hTmIqUtIDR3W9gOEhmh6CHhacEcZZH9xkZeMKlSvvVB5lunEr16yjykaP2RgxHrkyGqtcu6XybRGpch69uZX6iqbdzjE4sCqvzclmDsDrePQyvIsnz7f3w2wSa4ZQEyuIMFbWohlhVBkBUZJCba2F1BDFoCAzIqwQHHObQMhTQ3WSWJGkNNHUUjIA15132c4KM9embLzK5dKH8H4tK-Xk7k_pPuR7tZIMURzKCYLzjcBXn62pG7moWl-GzBIlGFMWIBaouKO0r-raG7u9gKD86Vvu9B34s7-xtvRvwQG46ICiqGVpFsU_om-An4Tt</recordid><startdate>20160922</startdate><enddate>20160922</enddate><creator>White, Nicholas J</creator><creator>Duong, Tran T</creator><creator>Uthaisin, Chirapong</creator><creator>Nosten, François</creator><creator>Phyo, Aung P</creator><creator>Hanboonkunupakarn, Borimas</creator><creator>Pukrittayakamee, Sasithon</creator><creator>Jittamala, Podjanee</creator><creator>Chuthasmit, Kittiphum</creator><creator>Cheung, Ming S</creator><creator>Feng, Yiyan</creator><creator>Li, Ruobing</creator><creator>Magnusson, Baldur</creator><creator>Sultan, Marc</creator><creator>Wieser, Daniela</creator><creator>Xun, Xiaolei</creator><creator>Zhao, Rong</creator><creator>Diagana, Thierry T</creator><creator>Pertel, Peter</creator><creator>Leong, F. 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Joel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antimalarial Activity of KAF156 in Falciparum and Vivax Malaria</atitle><jtitle>The New England journal of medicine</jtitle><addtitle>N Engl J Med</addtitle><date>2016-09-22</date><risdate>2016</risdate><volume>375</volume><issue>12</issue><spage>1152</spage><epage>1160</epage><pages>1152-1160</pages><issn>0028-4793</issn><eissn>1533-4406</eissn><abstract>With the emergence and spread of artemisinin resistance, new therapies for malaria are needed. This study shows that the imidazolopiperazine KAF156, a new antimalarial compound, has in vivo antimalarial activity.
Expanding artemisinin resistance and worsening partner-drug resistance in Southeast Asia threaten the global control of
Plasmodium falciparum
malaria.
1
–
5
New drugs are needed. KAF156 represents a new class of antimalarial agents (imidazolopiperazines)
6
identified by high-throughput phenotypic screening. KAF156 has potent in vitro activity against both asexual and sexual blood stages and the preerythrocytic liver stages of the malarial parasite.
7
The mechanism of antimalarial action is unknown, but drug resistance, mediated by mutations in the
P. falciparum
cyclic amine resistance locus (
PfCARL
) gene, which encodes a protein of unknown function, can be selected.
7
In a study of 70 healthy . . .</abstract><cop>United States</cop><pub>Massachusetts Medical Society</pub><pmid>27653565</pmid><doi>10.1056/NEJMoa1602250</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The New England journal of medicine, 2016-09, Vol.375 (12), p.1152-1160 |
| issn | 0028-4793 1533-4406 |
| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; New England Journal of Medicine |
| subjects | Administration, Oral Adult Antimalarial activity Antimalarial agents Antimalarials - administration & dosage Antimalarials - adverse effects Antimalarials - pharmacokinetics Antiparasitic agents Bradycardia Clinical trials Drug therapy Female Fever Humans Hyperbilirubinemia Hypokalemia Imidazoles - administration & dosage Imidazoles - adverse effects Imidazoles - pharmacokinetics Liver Malaria Malaria, Falciparum - drug therapy Malaria, Vivax - drug therapy Male Middle Aged Parasite Load Parasites Patients Piperazines - administration & dosage Piperazines - adverse effects Piperazines - pharmacokinetics Plasmodium falciparum - isolation & purification Plasmodium vivax - isolation & purification Thrombocytopenia Vomiting Young Adult |
| title | Antimalarial Activity of KAF156 in Falciparum and Vivax Malaria |
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