| Literature DB >> 32554597 |
Isaac A Klein1,2, Ann Boija1, Lena K Afeyan1,3, Susana Wilson Hawken1,3, Mengyang Fan4,5, Alessandra Dall'Agnese1, Ozgur Oksuz1, Jonathan E Henninger1, Krishna Shrinivas6,7, Benjamin R Sabari1, Ido Sagi1, Victoria E Clark1,8, Jesse M Platt1,9, Mrityunjoy Kar10, Patrick M McCall10,11,12, Alicia V Zamudio1,3, John C Manteiga1,3, Eliot L Coffey1,3, Charles H Li1,3, Nancy M Hannett1, Yang Eric Guo1, Tim-Michael Decker13, Tong Ihn Lee1, Tinghu Zhang4,5, Jing-Ke Weng1,3, Dylan J Taatjes13, Arup Chakraborty6,7,14,15,16,17,18, Phillip A Sharp3,18, Young Tae Chang19, Anthony A Hyman11,20, Nathanael S Gray4,5, Richard A Young21.
Abstract
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.Entities:
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Year: 2020 PMID： 32554597 DOI： 10.1126/science.aaz4427
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728