Towards Identifying Potent New Hits for Glioblastoma

Sherer, Christopher and Prabhu, Saurabh and Adams, David and Hayes, Joseph and Rowther, Farzana and Tolaymat, Ibrahim and Warr, Tracy and Snape, Timothy J. (2018) Towards Identifying Potent New Hits for Glioblastoma. MedChemComm, 11 (9). pp. 1850-1861. ISSN 2040-2511

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Official URL: http://dx.doi.org/10.1039/C8MD00436F

Abstract

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 Page 1 of 29 MedChemComm development of a new therapy in this area, with particular promise shown against glioblastoma subtypes that are resistant to conventional chemotherapeutic agents.

Item Type: Journal Article
Keywords: scaffold, glioblastoma, cancer, SAR, similarity screening
Faculty: Faculty of Medical Science
Depositing User: Ibrahim Tolaymat
Date Deposited: 09 Oct 2018 14:16
Last Modified: 21 Dec 2018 14:20
URI: http://arro.anglia.ac.uk/id/eprint/703634

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