Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: Targeting MDM2 by the small molecule RITA: towards the development of new multi-target drugs against cancer | Theoretical Biology and Medical Modelling BioMed Central Research Open Access Targeting MDM2 by the small molecule RITA towards the development of new multi-target drugs against cancer L Michel Espinoza-Fonseca Address Department of Biochemistry Molecular Biology and Biophysics University of Minnesota Minneapolis 55455 MN USA Email L Michel Espinoza-Fonseca - mef@ Corresponding author Published 20 September 2005 Received II July 2005 Theoretical Biology and Medical Modelling 2005 2 38 doi 1742-4682-2-38 Accepted 20 September 2005 This article is available from http content 2 I 38 2005 Espinoza-Fonseca licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http licenses by which permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited. Abstract Background The use of low-molecular-weight non-peptidic molecules that disrupt the interaction between the p53 tumor suppressor and its negative regulator MDM2 has provided a promising alternative for the treatment of different types of cancer. Among these compounds RITA reactivation of p53 and induction of tumor cell apoptosis has been shown to be effective in the selective induction of apoptosis and this effect is due to its binding to the p53 tumor suppressor. Since biological systems are highly dynamic and MDM2 may bind to different regions of p53 new alternatives should be explored. On this basis the computational blind docking approach was employed in this study to see whether RITA would bind to MDM2. Results It was observed that RITA binds to the MDM2 p53 transactivation domain-binding cleft. Thus RITA can be used as a lead compound for designing improved multi-target drugs. This novel strategy could provide enormous benefits to enable effective anti-cancer strategies. Conclusion This study has demonstrated that a single
