From an MCR fragment library, two novel chemical series have been developed as inhibitors of RET, which is a kinase involved in the pathology of medullary thyroid cancer (MTC). Structure activity relationship studies (SAR) identified two sub-micromolar tractable leads, 6g and 13g. 6g was confirmed to be a Type-II RET inhibitor. 13g and 6g inhibited RET in cells transformed by RET/C634. A RET DFG-out homology model was established and utilized to predict Type-II inhibitor binding modes.
Identification of two novel RET kinase inhibitors through MCR-based drug discovery: design, synthesis and evaluation / Frett, B; Moccia, M; Carlomagno, Francesca; Santoro, Massimo; Li, Hy. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 86:(2014), pp. 714-723. [10.1016/j.ejmech.2014.09.023]
Identification of two novel RET kinase inhibitors through MCR-based drug discovery: design, synthesis and evaluation
Moccia M;CARLOMAGNO, Francesca;SANTORO, MASSIMO;
2014
Abstract
From an MCR fragment library, two novel chemical series have been developed as inhibitors of RET, which is a kinase involved in the pathology of medullary thyroid cancer (MTC). Structure activity relationship studies (SAR) identified two sub-micromolar tractable leads, 6g and 13g. 6g was confirmed to be a Type-II RET inhibitor. 13g and 6g inhibited RET in cells transformed by RET/C634. A RET DFG-out homology model was established and utilized to predict Type-II inhibitor binding modes.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
