Hsp90 is an established anti-apoptotic target in cancer therapy [1]. Most of the known small-molecule inhibitors that have shown potent antitumor activity target the Hsp90 N-terminal domain and directly inhibit its ATP-ase activity [2], although displaying important secondary effects. A different approach to Hsp90 inhibition consists of targeting the protein C-terminal domain (CTD) and modulating its chaperone activity through allosteric effects. An original computational approach [3] and a combination of virtual and experimental screening enabled identification of 1 (Eupomatenoid-2, Fig. 1) as a lead for further development [3]. Chemical approaches to the (glyco)diversification at R4 (Figure 1) will be presented [4] and preliminary results indicate that the compounds obtained so far are CTD ligands and are able to accelerate Hsp90 ATPase activity.

Benzofurans as allosteric activators of Hsp90 ATPase activity / S. Sattin, L. Morelli, M. Panza, G. Vettoretti, E. Moroni, J. Tao, D. Agard, G. Colombo, A. Bernardi. ((Intervento presentato al 14. convegno Sigma-Aldrich Young Chemists Symposium tenutosi a Riccione nel 2014.

Benzofurans as allosteric activators of Hsp90 ATPase activity

S. Sattin
;
L. Morelli
Secondo
;
A. Bernardi
Ultimo
2014-10-29

Abstract

Hsp90 is an established anti-apoptotic target in cancer therapy [1]. Most of the known small-molecule inhibitors that have shown potent antitumor activity target the Hsp90 N-terminal domain and directly inhibit its ATP-ase activity [2], although displaying important secondary effects. A different approach to Hsp90 inhibition consists of targeting the protein C-terminal domain (CTD) and modulating its chaperone activity through allosteric effects. An original computational approach [3] and a combination of virtual and experimental screening enabled identification of 1 (Eupomatenoid-2, Fig. 1) as a lead for further development [3]. Chemical approaches to the (glyco)diversification at R4 (Figure 1) will be presented [4] and preliminary results indicate that the compounds obtained so far are CTD ligands and are able to accelerate Hsp90 ATPase activity.
Hsp90; benzofuran; allosteric modulation
Settore CHIM/06 - Chimica Organica
Benzofurans as allosteric activators of Hsp90 ATPase activity / S. Sattin, L. Morelli, M. Panza, G. Vettoretti, E. Moroni, J. Tao, D. Agard, G. Colombo, A. Bernardi. ((Intervento presentato al 14. convegno Sigma-Aldrich Young Chemists Symposium tenutosi a Riccione nel 2014.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/249581
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