CR13626: A Promising Oral Multi-Kinase Inhibitor for Glioblastoma Treatment in Mice

The abstract discusses the development of a new drug candidate, CR13626, for glioblastoma, a severe brain cancer with no cure. The drug targets tyrosine kinases (TKs), particularly receptor tyrosine kinases (RTKs) like EGFR and KDR, which are significant in tumor growth and blood vessel formation. The study evaluates CR13626's ability to penetrate the blood-brain barrier and its efficacy against GBM in both in vitro and in vivo tests.

CR13626 was tested against 173 kinase enzymes and showed potent inhibition of TKs associated with GBM, with IC50 values in the nanomolar range. The drug was effective in reducing the proliferation of various human GBM cell lines and demonstrated a significant reduction in tumor growth in an orthotopic mouse model, leading to an increase in the median survival rate of the treated animals.

Pharmacokinetic studies revealed that CR13626 has good oral bioavailability and can cross into the brain, with a brain/plasma ratio of 1.4. The drug's ability to penetrate the blood-brain barrier and inhibit multiple TKs, coupled with its impact on reducing tumor growth and extending survival in mice, supports its potential as a drug candidate for glioblastoma treatment.

The research was presented at the American Association for Cancer Research Annual Meeting in 2020, with Chiara Galimberti and colleagues as authors.