Contacts:
Tel: 050 2219582
e-mail: andrea.bacci@phd.unipi.it
Supervisors:
Prof. Simona Rapposelli
PhD project Title:
Design and synthesis of novel dual BTK-TCL1 inhibitors for the treatment of lymphoma
Research summary:
Targeting of Bruton tyrosine kinase (BTK) has shown as a novel therapeutic approach for lymphoproliferative disorders, however, is observed a drug-resistance due the selection of tumour clones bearing a mutated BTK and activation of alternative signalling pathways such as AKT and NF-kB. All these pathways are also co-activated through the interaction with TCL1 (T-cell leukemia/lymphoma 1), an important and so-far “undruggable” protein. A multi-target approach, aimed at obtain a simultaneous inhibition of both proteins with a single compound, could represent an innovative strategy for the treatment of lymphoma and an opportunity for preventing drug-resistance mechanisms. The aim of this project is to design and synthetize dual BTK-TCL1 inhibitors able to directly act against the mutated BTK forms but also against the AKT and NF-kB pathway activation, indirectly mediated by TCL1.