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.
2014
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]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/602195
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 20
  • ???jsp.display-item.citation.isi??? 19
social impact