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Anticancer Drugs Ceritinib Medicine Oncology Pharmacology Physiotherapy

Ceritinib (Mechanism of Action)

In this article we will discuss Ceritinib (Mechanism of Action)

In this article, we will discuss Ceritinib (Mechanism of Action). So, let’s get started.

Mechanism of Action

Ceritinib is a kinase inhibitor. Targets of ceritinib inhibition identified in either biochemical or cellular assays at clinically
relevant concentrations include ALK, insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (InsR), and ROS1.
Among these, ceritinib is most active against ALK. Ceritinib inhibited autophosphorylation of ALK, ALK-mediated phosphorylation of the downstream signaling protein STAT3, and proliferation of ALK-dependent cancer cells in in vitro and in vivo assays.

Ceritinib inhibited the in vitro proliferation of cell lines expressing EML4-ALK and NPM-ALK fusion proteins and demonstrated dose-dependent inhibition of EML4-ALK-positive NSCLC xenograft growth in mice and rats. Ceritinib exhibited dose-dependent anti-tumor activity in mice bearing EML4-ALK-positive NSCLC xenografts with demonstrated resistance to crizotinib, at concentrations within a clinically relevant range.

Pharmacodynamics

Cardiac Electrophysiology
Twelve of 919 patients (1.3%) treated with Ceritinib 750 mg once daily under fasted conditions with at least one post-baseline ECG assessment were found to have a QTc > 500 msec and 58 patients (6%) had an increase from baseline QTc > 60 msec. In ASCEND-4, a central tendency analysis of the QTc data at average steady-state concentrations demonstrated that the upper bound of the 2-sided 90% CI for QTc was 15.3 msec at Ceritinib 750 mg once daily under fasted conditions. A pharmacokinetic/pharmacodynamic analysis suggested concentration-dependent QTc interval
prolongation.

Ten of 925 patients (1.1%) had bradycardia defined as < 50 beats/minute.

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