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NUDT15 polymorphism...
NUDT15 polymorphism influences the metabolism and therapeutic effects of acyclovir and ganciclovir
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- Nishii, Rina (author)
- St Jude Children´s Research Hospital, Memphis
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- Mizuno, Takanori (author)
- National Center for Child Health and Development
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- Rehling, Daniel (author)
- Stockholm University,Stockholms universitet,Institutionen för biokemi och biofysik
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- Smith, Colton (author)
- St Jude Children´s Research Hospital, Memphis
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- Clark, Brandi L. (author)
- St Jude Children´s Research Hospital, Memphis
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- Zhao, Xujie (author)
- St Jude Children´s Research Hospital, Memphis
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- Brown, Scott A. (author)
- St Jude Children´s Research Hospital, Memphis
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- Smart, Brandon (author)
- St Jude Children´s Research Hospital, Memphis
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- Moriyama, Takaya (author)
- St Jude Children´s Research Hospital, Memphis
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- Yamada, Yuji (author)
- National Center for Child Health and Development
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- Ichinohe, Tatsuo (author)
- Hiroshima University Hospital
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- Onizuka, Makoto (author)
- Tokai University School of Medicine
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- Atsuta, Yoshiko (author)
- Japanese Data Center for Hematopoietic Cell Transplantation
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- Yang, Lei (author)
- St Jude Children´s Research Hospital, Memphis
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- Yang, Wenjian (author)
- St Jude Children´s Research Hospital, Memphis
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- Thomas, Paul G. (author)
- St Jude Children´s Research Hospital, Memphis
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- Stenmark, Pål (author)
- Stockholm University,Lunds universitet,Stockholms universitet,Institutionen för biokemi och biofysik,Lund University, Sweden,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Strukturell biokemi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Department of Experimental Medical Science,Faculty of Medicine,Structural Biochemistry,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Kato, Motohiro (author)
- National Center for Child Health and Development
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- Yang, Jun J. (author)
- St Jude Children´s Research Hospital, Memphis
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(creator_code:org_t)
- 2021-07-07
- 2021
- English.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Abstract
Subject headings
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- Nucleobase and nucleoside analogs (NNA) are widely used as anti-viral and anti-cancer agents, and NNA phosphorylation is essential for the activity of this class of drugs. Recently, diphosphatase NUDT15 was linked to thiopurine metabolism with NUDT15 polymorphism associated with drug toxicity in patients. Profiling NNA drugs, we identify acyclovir (ACV) and ganciclovir (GCV) as two new NNAs metabolized by NUDT15. NUDT15 hydrolyzes ACV and GCV triphosphate metabolites, reducing their effects against cytomegalovirus (CMV) in vitro. Loss of NUDT15 potentiates cytotoxicity of ACV and GCV in host cells. In hematopoietic stem cell transplant patients, the risk of CMV viremia following ACV prophylaxis is associated with NUDT15 genotype (P = 0.015). Donor NUDT15 deficiency is linked to graft failure in patients receiving CMV-seropositive stem cells (P = 0.047). In conclusion, NUDT15 is an important metabolizing enzyme for ACV and GCV, and NUDT15 variation contributes to inter-patient variability in their therapeutic effects.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- Antiviral
- acyclovir
- ganciclovir
- NUDT15
- SNP
- CMV
- Biochemistry
- biokemi
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Nishii, Rina
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Mizuno, Takanori
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Rehling, Daniel
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Smith, Colton
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Clark, Brandi L.
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Zhao, Xujie
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show more...
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Brown, Scott A.
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Smart, Brandon
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Moriyama, Takaya
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Yamada, Yuji
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Ichinohe, Tatsuo
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Onizuka, Makoto
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Atsuta, Yoshiko
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Yang, Lei
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Yang, Wenjian
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Thomas, Paul G.
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Stenmark, Pål
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Kato, Motohiro
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Yang, Jun J.
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
- Articles in the publication
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Nature Communica ...
- By the university
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Stockholm University
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Lund University