Glioblastoma is the most malignant primary brain cancer. It is characterized by high grade of proliferation, invasiveness, and angiogenesis, all of which contribute to poor prognosis. Median survival is about 15 months from diagnosis.
Mutations and alterations of key cellular pathways, including tyrosine kinases, are involved in the pathogenesis of glioblastoma, and currently there is no cure for this type of cancer. Tumour heterogeneity and presence of the blood brain barrier, with efflux transporters, are among the main causes of failure of novel therapeutic agents. Thus, appropriate target selectivity and pharmacokinetics (including brain penetration) are critical issues for the generation of potential drug candidates.
CR13626 is a novel, potent inhibitor of selected tyrosine kinases relevant to glioblastoma (FYN, YES, VEGFR2 and EGFR). CR13626 crosses efficiently the blood brain barrier and is not a substrate of P-gp and BCRP multidrug efflux transporters involved in brain tumour resistance, thus providing high brain concentrations of the active compound. CR13626 decreases the proliferation of different human glioblastoma cell lines and reduces tumour growth, eventually prolonging survival, in an orthotopic mouse model of glioblastoma.
These experimental findings draw a unique pharmacological profile for CR13626, making it an excellent candidate for development as a new drug for the therapy of glioblastoma.
Rottapharm Biotech is looking for a partnership to progress the compound into preclinical and clinical development.