Climate Change Data Portal
| DOI | 10.1126/science.aaz4427 |
| Partitioning of cancer therapeutics in nuclear condensates | |
| Klein I.A.; Boija A.; Afeyan L.K.; Hawken S.W.; Fan M.; Dall'Agnese A.; Oksuz O.; Henninger J.E.; Shrinivas K.; Sabari B.R.; Sagi I.; Clark V.E.; Platt J.M.; Kar M.; McCall P.M.; Zamudio A.V.; Manteiga J.C.; Coffey E.L.; Li C.H.; Hannett N.M.; Guo Y.E.; Decker T.-M.; Lee T.I.; Zhang T.; Weng J.-K.; Taatjes D.J.; Chakraborty A.; Sharp P.A.; Chang Y.T.; Hyman A.A.; Gray N.S.; Young R.A. | |
| 发表日期 | 2020 |
| ISSN | 0036-8075 |
| 起始页码 | 1386 |
| 结束页码 | 1392 |
| 卷号 | 368期号:6497 |
| 英文摘要 | The nucleus contains diverse phase-separated condensates that compartmentalize and concentrate biomolecules with distinct physicochemical properties. Here, we investigated whether condensates concentrate small-molecule cancer therapeutics such that their pharmacodynamic properties are altered. We found that antineoplastic drugs become concentrated in specific protein condensates in vitro and that this occurs through physicochemical properties independent of the drug target. This behavior was also observed in tumor cells, where drug partitioning influenced drug activity. Altering the properties of the condensate was found to affect the concentration and activity of drugs. These results suggest that selective partitioning and concentration of small molecules within condensates contributes to drug pharmacodynamics and that further understanding of this phenomenon may facilitate advances in disease therapy. © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works |
| 关键词 | cancercondensatediseasedrugphysicochemical propertyproteintumorantineoplastic agentBRD4 protein, humancell cycle proteingreen fluorescent proteinheterochromatin-specific nonhistone chromosomal protein HP-1MED1 protein, humannonhistone proteinnuclear proteinnucleophosminperoxisome proliferator activated receptor binding proteinrecombinant proteinserine arginine rich splicing factorSRSF2 protein, humantranscription factorcell nucleusdrug resistancegeneticshumanmetabolismneoplasmAntineoplastic AgentsCell Cycle ProteinsCell NucleusChromosomal Proteins, Non-HistoneDrug Resistance, NeoplasmGreen Fluorescent ProteinsHumansMediator Complex Subunit 1NeoplasmsNuclear ProteinsRecombinant ProteinsSerine-Arginine Splicing FactorsTranscription Factors |
| 语种 | 英语 |
| 来源机构 | Science |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/133408 |
| 推荐引用方式 GB/T 7714 | Klein I.A.,Boija A.,Afeyan L.K.,et al. Partitioning of cancer therapeutics in nuclear condensates[J]. Science,2020,368(6497). |
| APA | Klein I.A..,Boija A..,Afeyan L.K..,Hawken S.W..,Fan M..,...&Young R.A..(2020).Partitioning of cancer therapeutics in nuclear condensates.,368(6497). |
| MLA | Klein I.A.,et al."Partitioning of cancer therapeutics in nuclear condensates".368.6497(2020). |
| 条目包含的文件 | 条目无相关文件。 | |||||
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。
