A major breakthrough in science! Separation of rich chemotherapy drugs, affecting its anti-cancer efficacy!

, June 23, 2020 /PRNewswire/ --the discovery
of synthetic compounds forming concentrated droplets in cells could shake up drug research -- including the search for treatment sedovirusesthe pharmaceutical industry has a long-standing assumption that when drug molecules enter cells, they spread evenly -- but, says biologist Rick Young, "it's a far cry from the truth."In a recent study published in the journal Science, Young and his colleagues at the Whitehead Institute in Cambridge, Massachusetts, showed that anticancer drug compounds gather at precise locations in cells -- due to a phenomenon called phase separation, in which all cells separate their contentsphoto source: Science
these results challenge the underlying assumptions about the role, dynamics, and distribution of small molecule therapiesThey have led new strategies for the design of new coronavirus drugs and may help explain why so many of the treatments that work in the lab ultimately fail to treat humans"This paper promises to reshape our understanding of drug metabolism and drug-targeted cells," said Jonathon Ditlev, a cell biophysicist at Children's Hospital in Toronto, Canadabiomaterials have an easy way to establish order within cellsLike small spots in lava lamps or droplets of oil in water, proteins, RNA, and other cellular components can self-organize liquid droplets called condensates, which help separate cells insideresearchers have previously shown that this effect occurs in natural molecules, but the latest work suggests that synthetic compounds can be selectively isolated in droplets in a similar wayThis phenomenon can be used to enable certain drugs to hit targets more effectively, while limiting the unintended toxicity that causes harmful side effects"If we can start to understand how these condensates distinguish between small molecules, we can begin to develop existing condensate methods so that we can better treat diseases,"ditlev saidIn the study, The Cisplatingathered in , Young and his team tracked the dynamics of five small molecule cancer drugs in condensate, test tube experiments and cultured human cancer cells They began using cisplatin, the basis of many chemotherapy regimens By mixing cisplatin with known condensed proteins in the nucleus, the researchers found that cisplatin selectively gathers in droplets formed by a gene-activated protein called MED1 where MED1 is found, cisplatin molecules come together: the concentration of the drug inside the condensate is 600 times higher than the outside The researchers found that MED1 primarily acts on cancer-promoting genes, so cisplatin eventually targets the same DNA with its toxic platinum atoms -- essentially attacking the most painful parts of cancer cells effects also seem to affect drug resistance The team found that breast cancer drug, moxifen, also condenses in MED1 clots But mED1 levels of mED1 produced by cancer cells that are resistant to moxifen are much higher, and the team found that this caused the concentrate to expand, dilute the drug and impair its effectiveness "Every cancer drug we examined found that they were concentrated in these separate discombinants, " Young said "I don't know of a case where i can ignore that." the team is now trying to figure out why the drug molecules enter the condensate state "If we can learn more about the 'grammar' of molecules, then we may be able to modify small molecules so that they are concentrated in the right place," said Isaac Klein, a oncologist at the Whitehead Institute coronavirus condensate
Klein and ann Boija, a molecular biologist at the Whitehead Institute and co-author of the paper, have sat on the work of fighting SARS-CoV-2, a coronavirus that causes COVID-19, over the past two months photo source: Science
In unpublished experiments, they found that three key viral proteins associated with the SARS-CoV-2 replication mechanism came together to form a cohesion that absorbs and concentrates drug compounds "This is the result of the screening we need to start screening to see if small molecules have the ability to inhibit the replication of viral RNA and selectively split into condensate where replication occurs," said Young "In a rigorous trial, the only antiviral drug that has been shown to have an effect on COVID-19 is a molecule called Redsewe, which offers only limited benefits, which Young suspects may be due to the separation of the drug phase separation is part of "from now on is becoming a drug discovery," said Mark Murcko, chief science officer at Dewpoint Therapeutics in Boston, a young company founded in 2018 by Tony Hyman, a cell biolog
y at the Max Planck Institute for Sub-
Cell Biology and the Genetics
Institute Dewpoint's goal is to develop drugs in the biology of condensation, to function by destroying disease-related condensation, or by accumulating specific condensations in cells but not everyone believes it Robert Tjian, a biochemist at the University of California, Berkeley, says that while there are other mechanisms that explain how natural and synthetic molecules accumulate within cells, scientists are eager to link condensation to a variety of biological processes He worries that the excitement generated by papers like Young's could trigger research into drug design into phase-separation droplets that may only exist in the lab (BioValleyBioon.com) reference: How Or cancer drugs find their sle s le to a new toolset for drug how cells 'lava lamp' effect make cancer drugs more more "
of cancer sin nuclear scospheres " Science 19 Jun 2020: Vol 368, Issue 6497, pp 1386-1392 DOI: 10.1126/science.aaz4427