Ceritinib (LDK378)
CAS#: 1032900-25-6 (free base); 1380575-43-8 (2HCl); 1190399-48-4 (xHCl).
Description: Ceritinib, also known as LDK378, is a selective inhibitor of ALK1, a target found in metastatic non-small cell lung cancer (NSCLC). In Phase I trials, LDK378 showed a marked clinical response in 78 patients with anaplastic lymphoma kinase positive (ALK+) metastatic non-small cell lung cancer (NSCLC) who had progressed during or after crizotinib therapy or had not been previously treated with crizotinib. LDK378 blocks the ALK protein and stops it sending growth signals to cancer cells, which may stop them growing. Ceritinib was approved in April 2014.
Synonym: LDK-378; LDK378; LDK 278; Ceritinib, brand name: Zykadia.
IUPAC/Chemical Name: 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine
THEORETICAL ANALYSIS
Name: Ceritinib (LDK378)
CAS#: 1032900-25-6 (free base); 1380575-43-8 (2HCl); 1190399-48-4 (xHCl).
Chemical Formula: C28H36ClN5O3S
Exact Mass: 557.22274
Molecular Weight: 558.14
Elemental Analysis: C, 60.25; H, 6.50; Cl, 6.35; N, 12.55; O, 8.60; S, 5.75
TECHNICAL DATA
ADDITIONAL INFORMATION
Ceritinib (Zykadia) is a drug for the treatment of lung cancer. It is an ALK inhibitor. It was approved in April 2014 by the Food and Drug Administration for the treatment of ALK-positive metastatic non-small cell lung cancer (NSCLC) following treatment with crizotinib.
Initial results from a Phase I study investigating the maximum tolerated dose, safety, pharmacokinetics and antitumor activity of LDK378 in 88 patients with ALK+ advanced malignancies, as detected by an FDA-approved test and who had progressed during treatment with, or were intolerant to, crizotinib, were presented at the European Society of Medical Oncology 2012 annual congress. The data showed marked responses in a majority of patients with ALK+ NSCLC. A response rate (including complete response [CR], partial response [PR] and unconfirmed PR) of 80% was observed in the patients who had experienced disease progression after crizotinib treatment. Novartis has initiated two Phase II clinical trials to further evaluate the compound in this patient population with plans to initiate several Phase III clinical trials later this year. First regulatory filing is anticipated by early 2014. (http://www.novartis.com/newsroom/media-releases/en/2013/1685517.shtml)
REFERENCES
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