Characterizing the relationship between the chemical structures of drugs and their activities on primary cultures of pediatric solid tumors.
2021
Background Despite continued efforts to develop new treatments, there is an urgent need to discover new drug leads to treat tumours exhibiting primary or secondary resistance to exiting drugs. Cell cultures derived from patient-derived orthotopic xenografts are promising pre-clinical models to better predict drug response in cancer recurrence. Objective The aim of the study was to investigate the relationship between the physiochemical properties of drugs and their in vitro potency as well as identifying chemical scaffolds biased towards selectivity or promiscuity of such drugs. Methods The bioactivities of 158 drugs screened against cell cultures derived from 30 cancer orthotopic patient-derived xenograft (O-PDX) models were considered. Drugs were represented by physicochemical descriptors and chemical structure fingerprints. Supervised learning was employed to model the relationship between features and in vitro potency. Results Drugs with in vitro potency for alveolar rhabdomyosarcoma and osteosarcoma tend to have a higher number of rings, two carbon-hetero bonds and halogens. Selective and promiscuous scaffolds for these phenotypic targets were identified. Highly-predictive models of in vitro potency were obtained across these 30 targets, which can be applied to unseen molecules via a webserver (https://rnewbie.shinyapps.io/Shobek-master). Conclusion It is possible to identify privileged chemical scaffolds and predict the in vitro potency of unseen molecules across these 30 targets This information and models should be helpful to select which molecules to screen against these primary cultures of pediatric solid tumors.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
0
References
0
Citations
NaN
KQI