Neuroblastoma (NB) represents the most common extracranial paediatric solid tumor for which no specific FDA-approved treatment is currently available. The tyrosine kinase c-Src has been reported to play an important role in the differentiation, cell-adhesion and survival of NB cells. Starting from dual Src/Abl inhibitors previously found active in NB cell lines (1–3), small modification of the original structures almost abolished the Abl activity with a contemporary improvement of affinity and specificity for c-Src. Among the synthesized compounds, the most potent c-Src inhibitor (10a) showed a very interesting antiproliferative activity in SH-SY5Y cells with an IC50 of 80 nM and a favourable ADME profile. A 3D SAR analysis was also attempted and may guide the design of more potent c-Src inhibitors as potential agents for NB treatment.

Botta, M., Brullo, C., Crespan, E., Tintori, C., Musumeci, F., Biava, M., et al. (2011). Identification of potent c-Src inhibitors strongly affecting the proliferation of human neuroblastoma cells. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 21, 5928-5933 [10.1016/j.bmcl.2011.07.079].

Identification of potent c-Src inhibitors strongly affecting the proliferation of human neuroblastoma cells.

BOTTA, MAURIZIO;TINTORI, CRISTINA;DREASSI, ELENA;ZAMPERINI, CLAUDIO;
2011

Abstract

Neuroblastoma (NB) represents the most common extracranial paediatric solid tumor for which no specific FDA-approved treatment is currently available. The tyrosine kinase c-Src has been reported to play an important role in the differentiation, cell-adhesion and survival of NB cells. Starting from dual Src/Abl inhibitors previously found active in NB cell lines (1–3), small modification of the original structures almost abolished the Abl activity with a contemporary improvement of affinity and specificity for c-Src. Among the synthesized compounds, the most potent c-Src inhibitor (10a) showed a very interesting antiproliferative activity in SH-SY5Y cells with an IC50 of 80 nM and a favourable ADME profile. A 3D SAR analysis was also attempted and may guide the design of more potent c-Src inhibitors as potential agents for NB treatment.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11365/20754
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