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Chang, Young Tae
복잡계 자기조립 연구단
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Partitioning of cancer therapeutics in nuclear condensates

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Title
Partitioning of cancer therapeutics in nuclear condensates
Author(s)
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.; Young Tae Chang; Hyman A.A.; Gray N.S.; Young R.A.
Subject
PHASE-SEPARATION, ; TRANSCRIPTIONAL ADDICTION, ; SUBCELLULAR-DISTRIBUTION, ; DISORDERED PROTEINS, ; SUPER-ENHANCERS, ; CELL IDENTITY, ; C-MYC, ; RESISTANCE, ; CISPLATIN, ; MITOXANTRONE
Publication Date
2020-06
Journal
SCIENCE, v.368, no.6497, pp.1386 - 1392
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
Abstract
© 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. 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
URI
https://pr.ibs.re.kr/handle/8788114/7819
DOI
10.1126/science.aaz4427
ISSN
0036-8075
Appears in Collections:
Center for Self-assembly and Complexity(복잡계 자기조립 연구단) > 1. Journal Papers (저널논문)
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