Discovery and Evaluation of Clinical Candidate AZD3759, a Potent, Oral Active, Central Nervous System-Penetrant, Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor.
ID: CHEMBL3621142
Journal: J Med Chem
Title: Discovery and Evaluation of Clinical Candidate AZD3759, a Potent, Oral Active, Central Nervous System-Penetrant, Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor.
Authors: Zeng Q, Wang J, Cheng Z, Chen K, Johnström P, Varnäs K, Li DY, Yang ZF, Zhang X.
Abstract: Recent reports 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 (4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl (2R)-2,4-dimethylpiperazine-1-carboxylate 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.
CiteXplore: 26313252
Patent ID: ---
Assay Summary
Total
95
A - ADME
B - Binding
F - Functional
P - Physicochemical
T - Toxicity
Bioactivity Summary
Total
290
AUC
IC50
Fu
Papp
Ratio
K(p,uu,CSF)
K(p,uu,brain)
Inhibition
T1/2
CL
F
Vdss
Activity
Cmax
BPR
Ratio IC50
Solubility
Tmax
CLH
Drug metabolism