As part of our ongoing investigations into the development of novel STAT3 inhibitors, through a computational repositioning approach, we identified the 5,6-dimethyl-1,3-dihydrobenzo[c][1,2,5] thiadiazole-2,2- dioxide I (NCI database, Figure 1) as a new candidate targeting the STAT3 SH2 domain. Since it exhibited an interesting inhibitory activity (inh. % = 81.6 at 30 μM), we investigated the molecular basis of its binding mode by synthesizing a set of derivatives showing different substitution patterns (Figure 1). The SAR study on these analogues highlighted several essential features to ensure inhibitory activity against STAT3. Furthermore, spectroscopic and spectrophotometric studies suggested a possible mechanism of interaction for product I. The results of our investigation will be presented.

5,6-Dimethyl-1,3-dihydrobenzo[c][1,2,5]thiadiazole-2,2-dioxide as new STAT3 inhibitor / S. Villa, M. Mori, F. Meneghetti, A. Pedretti, L. Regazzoni, D. Colombo, A. Asai, A. Gelain. ((Intervento presentato al convegno 26th National Meeting in Medicinal Chemistry and 12th Young Medicinal Chemists' Symposium tenutosi a Milano nel 2019.

5,6-Dimethyl-1,3-dihydrobenzo[c][1,2,5]thiadiazole-2,2-dioxide as new STAT3 inhibitor

S. Villa;M. Mori;F. Meneghetti;A. Pedretti;L. Regazzoni;D. Colombo;A. Gelain
2019-07

Abstract

As part of our ongoing investigations into the development of novel STAT3 inhibitors, through a computational repositioning approach, we identified the 5,6-dimethyl-1,3-dihydrobenzo[c][1,2,5] thiadiazole-2,2- dioxide I (NCI database, Figure 1) as a new candidate targeting the STAT3 SH2 domain. Since it exhibited an interesting inhibitory activity (inh. % = 81.6 at 30 μM), we investigated the molecular basis of its binding mode by synthesizing a set of derivatives showing different substitution patterns (Figure 1). The SAR study on these analogues highlighted several essential features to ensure inhibitory activity against STAT3. Furthermore, spectroscopic and spectrophotometric studies suggested a possible mechanism of interaction for product I. The results of our investigation will be presented.
Settore CHIM/08 - Chimica Farmaceutica
Settore CHIM/06 - Chimica Organica
Settore BIO/10 - Biochimica
Società Chimica Italiana. Divisione di Chimica Farmaceutica
Università degli studi di Milano
5,6-Dimethyl-1,3-dihydrobenzo[c][1,2,5]thiadiazole-2,2-dioxide as new STAT3 inhibitor / S. Villa, M. Mori, F. Meneghetti, A. Pedretti, L. Regazzoni, D. Colombo, A. Asai, A. Gelain. ((Intervento presentato al convegno 26th National Meeting in Medicinal Chemistry and 12th Young Medicinal Chemists' Symposium tenutosi a Milano nel 2019.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/732774
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