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. 2017 Dec 16;494(3-4):477-483.
doi: 10.1016/j.bbrc.2017.10.106. Epub 2017 Oct 21.

A Chemical Screen Identifies Trifluoperazine as an Inhibitor of Glioblastoma Growth

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A Chemical Screen Identifies Trifluoperazine as an Inhibitor of Glioblastoma Growth

Tiago Pinheiro et al. Biochem Biophys Res Commun. .

Abstract

Glioblastoma (GBM) is regarded as the most common malignant brain tumor but treatment options are limited. Thus, there is an unmet clinical need for compounds and corresponding targets that could inhibit GBM growth. We screened a library of 80 dopaminergic ligands with the aim of identifying compounds capable of inhibiting GBM cell line proliferation and survival. Out of 45 active compounds, 8 were further validated. We found that the dopamine receptor D2 antagonist trifluoperazine 2HCl inhibits growth and proliferation of GBM cells in a dose dependent manner. Trifluoperazine's inhibition of GBM cells is cell line dependent and correlates with variations in dopamine receptor expression profile. We conclude that components of the dopamine receptor signaling pathways are potential targets for pharmacological interventions of GBM growth.

Keywords: 6,7-ADTN HBr (PubChem CID: 11230706); Bromocriptine Mesylate (PubChem CID: 31100); Cancer; Cell lines; Chlorpromazine HCl (PubChem CID: 6240); Clozapine (PubChem CID: 2818); Dopamine; Glioblastoma; R(−)-Apomorphine (PubChem CID: 6005); S(−)-Raclopride l-Tartrate (PubChem CID: 11663304); SKF-83566 HCl (PubChem CID: 1243); Screening; Trifluoperazine; Trifluoperazine 2HCl (PubChem CID: 66064).

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