Tolaymat_2018.pdf (1.05 MB)
Towards Identifying Potent New Hits for Glioblastoma
journal contribution
posted on 2023-08-30, 15:39 authored by Christopher Sherer, Saurabh Prabhu, David Adams, Joseph Hayes, Farzana Rowther, Ibrahim Tolaymat, Tracy Warr, Timothy J. SnapeGlioblastoma 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.
History
Refereed
- Yes
Volume
11Issue number
9Page range
1850-1861Publication title
MedChemCommISSN
2040-2511External DOI
Publisher
Royal Society of ChemistryFile version
- Accepted version
Language
- eng
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Legacy posted date
2018-10-09Legacy creation date
2018-10-04Legacy Faculty/School/Department
Faculty of Health, Education, Medicine & Social CareUsage metrics
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