Among kinase inhibitors developed for oncology, Crizotinib stands out for combining oral bioavailability with ATP-competitive blockade of both c-Met and ALK catalytic activity. The compound, developed by Pfizer under the code PF-02341066, later reached market as Xalkori for ALK/ROS1-positive NSCLC. The Crizotinib molecular structure pairs a dichlorofluorophenyl-ethoxy pyridine core with a piperidinyl-pyrazole side chain. The identifier 877399-52-5 anchors the compound across pharmaceutical databases and supplier listings, separating it from structurally adjacent ALK-targeting molecules.
Application of Crizotinib
As a research tool, Crizotinib functions as a selective ATP-competitive inhibitor spanning four receptor tyrosine kinases - ALK, c-Met/HGFR, RON, and ROS1 - along with their oncogenic variants, including c-Met/HGFR mutations and ALK or ROS1 gene fusions. That multi-target reach makes the Crizotinib structure useful for distinguishing which kinase drives a given tumor's growth: EML4-ALK and NPM-ALK fusions respond specifically to ALK inhibition, while MET-amplified tumors depend on the compound's c-Met activity instead. Bulk material, including supply from an 877399-52-5 factory, should be checked against the CAS 877399-52-5 reference standard before use.
In Vitro
Enzymatic and cell-based assays place Crizotinib's potency at IC50 values of 20 nM against ALK and 8 nM against c-Met, with cellular phosphorylation assays showing comparable numbers - 24 nM for NPM-ALK and 11 nM for c-Met. Its third target, ROS1, binds even more tightly, with a Ki below 0.025 nM. In ALK-positive anaplastic large cell lymphoma lines, the compound suppressed proliferation at IC50 values near 30 nmol/L, triggering G1-S arrest and apoptosis, while ALK-negative lymphoma lines showed no such response.
In Vivo
Oral PF-2341066 given to immunodeficient mice carrying Karpas299 ALCL xenografts produced dose-dependent tumor response, with animals receiving 100 mg/kg daily achieving complete regression within two weeks. Twice-daily 250 mg oral dosing in patients reached steady-state plasma levels by day 15, linking the xenograft schedule to a clinically meaningful exposure window.
Biochemical and Physiological Actions
Roughly 43% of an oral dose of Crizotinib reaches systemic circulation, binding plasma proteins at 91% and undergoing hepatic clearance via CYP3A4/CYP3A5, with an elimination half-life near 42 hours. Within the Crizotinib chemical structure, the chiral center at the ethoxy linkage drives the molecule's target-binding geometry, explaining why only the R-enantiomer is active; a Crizotinib chemical structure diagram illustrates this spatial arrangement directly. Treatment also raised soluble MET, a c-MET pathway biomarker, confirming target engagement beyond enzymatic assays.
Features and Benefits of Crizotinib
Few kinase inhibitors match Crizotinib's reach across three oncogenic drivers - ALK, c-Met, and ROS1 - within one ATP-competitive scaffold. That versatility matters most for ROS1-positive non-small cell lung cancer, a subtype found in roughly 1-2% of US NSCLC cases and at a similar frequency in East Asian populations. A Crizotinib molecular structure diagram, paired with the compound's pharmacokinetic and pharmacodynamic record from xenograft studies through clinical trials, gives researchers a thoroughly mapped starting point for ALK/ROS1/MET pathway work.
