Potent, orally available and brain-penetrant ALK/ROS1 selective inhibitor (mean Ki value of <0.07 nM for inhibition of recombinant human wild-type ALK) displaying superior potency against all known clinically acquired ALK mutations (all displaying sub-nanomolar Ki values), including the highly resistant G1202R mutant. PF 06463922 (Lorlatinib) is capable of blocking Crizotinib-resistant ROS1 mutations and treatment with PF 06463922 led to superior regression of EML4-ALK-driven brain metastases compared with other clinically available ALK inhibitors.

KEYWORDS: PF 06463922 | supplier | ALK/ROS1 inhibitor | Lorlatinib | PF06463922 | CAS [1454846-35-5] | ALK | ROS | Inhibitor | RTK | receptor tyrosine kinase | c-ROS | G1202R | mutant | Crizotinib | EML4-ALK | oncogene | fusion protein | Anaplastic Lymphoma Kinase | insulin receptor