Bioorg Med Chem: scientists find new anticancer drugs, which are expected to reverse chemotherapy resistance

September 25, 2018 / BIOON / - one of the major disadvantages of chemotherapy is that as the treatment time goes on, tumor cells will develop drug resistance, thus increasing the probability of tumor recurrence Finding a way to inhibit drug resistance will be an important step to enhance the efficacy of anticancer drugs Photo source: bioorganic & Medical Chemistry 26 (2018) 4301-4309 recently M Kyle Hadden, a pharmacochemist from the University of Connecticut (UConn), and Dmitry, a molecular biologist from UConn health Korzhnev has found that several small molecular compounds can inhibit the ability of some cancer cells to avoid chemotherapy damage, which means that resistance begins to develop Trans lesion synthesis (TLS) is a DNA damage tolerance mechanism and a replication pathway that allows DNA damage (including DNA damage caused by tumor chemotherapy drugs) Previous studies have shown that inhibition of TLS can enhance the sensitivity of cancer cells to first-line chemotherapy drugs and reduce the formation of mutations related to chemotherapy resistance, which makes TLS signal pathway become a potential target for anticancer TLS is mediated by a heterogeneous protein complex consisting of a specific DNA polymerase, including the Y-family DNA polymerase Rev1 In the previous study, researchers developed a screening method to find the first small molecule that can disrupt the protein interaction between rev1-ct and the Rev1 binding region (RIR) in a variety of DNA polymerases involved in TLS process In this study, the researchers reported additional small molecular drugs that inhibit this key TLS protein protein protein interaction Through a series of Biochemistry, computational simulation and cell research, the preliminary structure activity relationship of these drugs was found, and their preliminary pharmacokinetic parameters were determined These molecules can be used as a combination of anti-cancer drugs to make long-term chemotherapy more effective Although these findings are encouraging, Hadden also said that the discovery is only the initial discovery, and new drug development is a long process, which will take 10 years or more More laboratory and clinical studies are needed to further explore the drug and push it to the clinic Reference: zuleyha ozen et al Small molecular scales that disrupt the rev1-ct / RIR protocol protocol interaction, bioorganic & Medical Chemistry (2018) Doi: 10.1016/j.bmc.2018.07.029