PTK2 PROTAC unveiled as a selective inhibitor of gastrointestinal neuroendocrine cell proliferation via multi-target drug screening

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Introduction: Gastrointestinal neuroendocrine tumors (GI-NETs) exhibit a complex and diverse nature, posing challenges in their effective treatment and management. While there have been advancements in treatment options, addressing the need for more effective and targeted therapies remains a significant issue, especially for patients with advanced or metastatic disease. Improving outcomes in the management of patients with GI-NETs is a key priority, and further research and development are crucial in this regard.

Aim(s): We employed a multi-target drug screening to find compounds that modulate specific molecular targets in neuroendocrine cells. This approach identifies potential neuroendocrine-specific compounds, minimizing off-target effects on other cell types.

Materials and methods: opnME drugs library was used to identify a compound targeting GI-NETs cells. Screening was performed with GI-NETs cell lines (GOT-1 and COLO320 DM) and using SW620 colon cancer cells as a control. Viability was measured using crystal violet, and apoptosis by caspase 3/7 activity. Protein expression and localization was asses by confocal microscopy, gene expression was measured by QPCR.

Conference:

Presenting Author: Gagliano T

Authors: Malavasi E, Toffoli L, Dainotto M, Gagliano T,

Keywords: Protac, PTK2, Screening, GI-NETs,