SYNERGISTIC INHIBITION OF THE HEDGEHOG PATHWAY BY NEWLY DESIGNED SMO AND GLI ANTAGONISTS BEARING THE ISOFLAVONE SCAFFOLD
M. CAIMANO, S. BERARDOZZI, F. BERNARDI, P. INFANTE, C. INGALLINA, S. TOSCANO, E. DE PAOLIS, R. ALFONSI, B. BOTTA, M. MORI, F. GHIRGA, L. DI MARCOTULLIO
SYNERGISTIC INHIBITION OF THE HEDGEHOG PATHWAY BY NEWLY DESIGNED SMO AND GLI ANTAGONISTS BEARING THE ISOFLAVONE SCAFFOLD
The Hedgehog (Hh) signalling pathway is evolutionarily conserved and its fine regulation is essentialfor proper development and tissues homeostasis. Aberrant activation of the Hh pathway is responsiblefor the onset of several malignancies, including medulloblastoma (MB), the most frequent pediatricbrain tumor. Small molecules able to block the pathway at the upstream receptor Smoothened (Smo) orthe downstream effector Gli1 have thus emerged recently as valuable anticancer agents. The aim of thisproposal is to discover novel powerful Smo and Gli inhibitors targeting Hh signaling at both upstreamand downstream level, and to investigate their pharmacological effects on MB.
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