Indications and Usage
Ceritinib is a new ALK gene inhibitor (ALKi) developed by Novartis Pharmaceuticals; its commercial name is Zykadia, and its previous code was LDK378. It was approved by the FDA for sale on April 29, 2014, and it is used to treat anaplastic lymphoma kinase (ALK) positive transfer of crizotinib (CRZ) progress or intolerance of non-small cell lung cancer (NSCLC).
Mechanisms of Action
Crizotinib resistance is a major issue for patients undergoing treatment for ALK gene rearrangement positive non-small cell lung cancer. Ceritinib is a kind of ALK tyrosine kinase inhibitor. Ceritinib does not target the MET proto-oncogene, but instead inhibits the insulin-like growth factor 1 receptor and blocks proteins from promoting cancer cell development, thus inhibiting the expression of EML4-ALK and NPM-ALK fusion protein cells. It is used to treat ALK rearrangement positive NSCLC patients who have previously used Crizotinib and can overcome Crizotinib resistance. Compared to Crizotinib, Ceritinib does not inhibit MET kinase activity, but inhibits IGF-1 receptors. Whether in terms of enzyme reaction, cell analysis or Crizotinib resistant animal models, research results all show that Ceritinib is more effective than Crizotinib. Additionally, regardless of any ALK resistance mutation, Ceritinib is still highly effective. In clinical models, Ceritinib’s ALK inhibition has 20 times the tumor-fighting effect of Crizotinib. Ceritinib also has the same effect on Crizotinib resistant central nervous system lesion NSCLC. Clinical trials show that Ceritinib can effectively inhibit ALK targets, potentially affecting an unknown kinase related to drug resistance, thus overcoming Crizotinib resistance.
American patent numbers: US7153964，US7893074，US7964592，US8039474，US8039479，US8377921，US8703787.
Patent expiration dates:
February 26, 2021 (US7153964)
April 25, 2026 (US7893074)
January 13, 2027 (US7964592)
June 29, 2030 (US8039474, US8039479)
November 20, 2027 (US8377921)
April 29, 2032 (US8703787)
Patents belong to Novartis
ChEBI: A member of the class of aminopyrimidines that is 2,6-diamino-5-chloropyrimidine in which the amino groups at positions 2 and 6 are respectively carrying 2-methoxy-4-(piperidin-4-yl)-5-methylphenyl and 2-(isopropylsulfonyl)phenyl substituents. Used for the
treatment of ALK-positive metastatic non-small cell lung cancer.