and Evaluation of Clinical Candidate AZD3759, a Potent, Oral Active, Central
Nervous System- Penetrant, Epidermal Growth Factor Receptor Tyrosine Kinase
Zeng Q, Wang J, Cheng Z, Chen
K, Johnstrom P, Varnas K, Li DY, Yang ZF, Zhang X.
Innovation Center China, Asia
& Emerging Markets iMed, AstraZeneca Innovative Medicines and Early
Development, Shanghai, China; AstraZeneca Translational Centre, Personal
Healthcare and Biomarkers iMed, AstraZeneca R&D, Stockholm, Sweden;
Karolinska Institutet, Centre for Psychiatry Research, Karolinska University
Hospital, Stockholm, Sweden.
suggest that an increasing number of patients with lung cancer, especially
those with activating mutations of the epidermal growth factor receptor (EGFR),
also present with brain metastases and leptomeningeal metastases. These
patients have poor prognosis as there are no approved drugs for these indications.
Available agents have poor efficacy for these patients even at well above their
standard dose. Herein, we report the discovery of
oxylate 1m (AZD3759), an investigational drug currently in Phase 1 clinical
trial, which has excellent central nervous system penetration and which induces
profound regression of brain metastases in a mouse model.