Design and synthesis of PARP inhibitors for an innovative anti-cancer therapy

Author

Grande Ribó, Núria

Abstract

Poly(ADP-ribose)polymerase (PARP) is a class of 17 enzymes involved in different physiological roles, such as DNA repair, apoptosis and stress oxidative response. The connection between these enzymes and the cancer proliferation emerged many years ago and PARP inhibition was confirmed as a good strategy to fight different types of cancers. Indeed, between 2014 and 2018, FDA and EMA approved 4 PARP inhibitors: olaparib, rucaparib, niraparib and talazoparib, as single agents or in combination with DNA alkylating drugs for the treatment of several cancers such as ovarian, breast, colon, and prostate. However, the most difficult challenge is the identification of derivatives able to selectively inhibit only one of the 17 subfamilies of PARPs.
In this scenario, the project is aimed at the design and synthesis of small molecules able to selectively inhibit PARP10 or 15, with the aim to get light on their physiological and pathological roles, by exploiting these compounds as chemical probes, as well as identifying new potential anticancer agents.

Director

Cuenca González, Ana Belén
Tabarrini, Oriana

Degree

IQS SE - Master’s Degree in Pharmaceutical Chemistry

Date

2022-09-08