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Issue 11, 2018
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Towards identifying potent new hits for glioblastoma

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Glioblastoma is a devastating disease of the brain and is the most common malignant primary brain tumour in adults. The prognosis for patients is very poor with median time of survival after diagnosis measured in months, due in part to the tumours being highly aggressive and often resistant to chemotherapies. Alongside the ongoing research to identify key factors involved in tumour progression in glioblastoma, medicinal chemistry approaches must also be used in order to rapidly establish new and better treatments for brain tumour patients. Using a computational similarity search of the ZINC database, alongside traditional analogue design by medicinal chemistry intuition to improve the breadth of chemical space under consideration, six new hit compounds (14, 16, 18, 19, 20 and 22) were identified possessing low micromolar activity against both established cell lines (U87MG and U251MG) and patient-derived cell cultures (IN1472, IN1528 and IN1760). Each of these scaffolds provides a new platform for future development of a new therapy in this area, with particular promise shown against glioblastoma subtypes that are resistant to conventional chemotherapeutic agents.

Graphical abstract: Towards identifying potent new hits for glioblastoma

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Publication details

The article was received on 31 Aug 2018, accepted on 01 Oct 2018 and first published on 02 Oct 2018

Article type: Research Article
DOI: 10.1039/C8MD00436F
Med. Chem. Commun., 2018,9, 1850-1861

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    Towards identifying potent new hits for glioblastoma

    C. Sherer, S. Prabhu, D. Adams, J. Hayes, F. Rowther, I. Tolaymat, T. Warr and T. J. Snape, Med. Chem. Commun., 2018, 9, 1850
    DOI: 10.1039/C8MD00436F

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