Scientific area
3.1 Basic medicine
Discipline(s)
Medicinal chemistry
Project title
Optimization of P-glycoprotein modulators and insights into the efflux mechanism
Scientific Coordinator's name:
Maria José Umbelino Ferreira
Scientific Coordinator's e-mail:
mjuferreira@ff.ul.pt
Principal R&D Unit:
iMed.UL/FFUL
Other R&D Units involved in the project:
Madeira University; Institute of Medical Microbiology, Szeged University; Institute of Pathology Charité Campus Mitte, Humbolt University; First Department of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University
Project keyword(s)
Multidrug resistance; P-glycoprotein modulators
Short abstract and comments
Multidrug resistance (MDR) is considered the major obstacle for successful cancer chemotherapy. MDR is associated to the overexpression of ABC-transporter proteins, such as P-glycoprotein (Pgp), which acts as an efflux pump for structurally and functionally unrelated chemotherapeutic agents. The broad goals of this project are: i) optimize macrocyclic diterpenes and cucurbitane-type triterpenes as leads for overcoming Pgp-mediated MDR, using QSAR, docking and molecular dynamics simulations along with in vitro and in vivo experiments; ii) unveil their binding modes with Pgp, using in silico and in vitro models and iii) get insight into the efflux mechanism from MD P-glycoprotein modeling.
Potential uses/indications
The project will contribute for overcoming MDR and for better understanding the efflux mechanism of ABC-transporters.
Status
Ongoing
Partner Status: Seeking Partners?
Yes
Grant number (QREN, FP7, Eureka, etc)
Grant number (QREN, FP7, Eureka, etc)
Last edited on
2013-11-04 16:34:30