1 research outputs found
Discovery of Clinical Candidate CEP-37440, a Selective Inhibitor of Focal Adhesion Kinase (FAK) and Anaplastic Lymphoma Kinase (ALK)
Analogues structurally related to
anaplastic lymphoma kinase (ALK)
inhibitor <b>1</b> were optimized for metabolic stability. The
results from this endeavor not only led to improved metabolic stability,
pharmacokinetic parameters, and in vitro activity against clinically
derived resistance mutations but also led to the incorporation of
activity for focal adhesion kinase (FAK). FAK activation, via amplification
and/or overexpression, is characteristic of multiple invasive solid
tumors and metastasis. The discovery of the clinical stage, dual FAK/ALK
inhibitor <b>27b</b>, including details surrounding SAR, in
vitro/in vivo pharmacology, and pharmacokinetics, is reported herein