| Literature DB >> 30710641 |
Nicola Colclough1, Kan Chen2, Peter Johnström3, Markus Fridén4, Dermot F McGinnity5.
Abstract
Due to the blood-brain barrier (BBB) limiting the exposure of therapeutics to the central nervous system (CNS), patients with brain malignancies are challenging to treat, typically have poor prognoses, and represent a significant unmet medical need. Preclinical data report osimertinib to have significant BBB penetration and emerging clinical data demonstrate encouraging activity against CNS malignancies. Here, we discuss the oncology drug candidates AZD3759 and AZD1390 as case examples of discovery projects designing in BBB penetrance. We demonstrate how these innovative kinase inhibitors were recognized as brain penetrant and outline our view of experimental approaches and strategies that can facilitate the discovery of new brain-penetrant therapies for the treatment of primary and secondary CNS malignancies as well as other CNS disorders.Entities:
Mesh：
Substances：
Year: 2019 PMID： 30710641 DOI： 10.1016/j.drudis.2019.01.015
Source DB: PubMed Journal: Drug Discov Today ISSN： 1359-6446 Impact factor: 7.851