WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205511
CAS#: 1032900-25-6 (free base)
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.
MedKoo Cat#: 205511
Name: Ceritinib (LDK378)
CAS#: 1032900-25-6 (free base)
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
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
InChi Key: VERWOWGGCGHDQE-UHFFFAOYSA-N
InChi Code: InChI=1S/C28H36ClN5O3S/c1-17(2)37-25-15-21(20-10-12-30-13-11-20)19(5)14-24(25)33-28-31-16-22(29)27(34-28)32-23-8-6-7-9-26(23)38(35,36)18(3)4/h6-9,14-18,20,30H,10-13H2,1-5H3,(H2,31,32,33,34)
SMILES Code: ClC1=CN=C(NC2=CC(C)=C(C3CCNCC3)C=C2OC(C)C)N=C1NC4=CC=CC=C4S(C(C)C)(=O)=O
1032900-25-6 (Ceritinib free base)
1380575-43-8 (Ceritinib 2HCl)
1190399-48-4 (Ceritinib xHCl).
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)
1: Nishio M, Murakami H, Horiike A, Takahashi T, Hirai F, Suenaga N, Tajima T, Tokushige K, Ishii M, Boral A, Robson M, Seto T. Phase I Study of Ceritinib (LDK378) in Japanese Patients with Advanced, Anaplastic Lymphoma Kinase-Rearranged Non-Small-Cell Lung Cancer or Other Tumors. J Thorac Oncol. 2015 May 27. [Epub ahead of print] PubMed PMID: 26020125.
2: Biya J, Caramella C, Lindsay CR, Planchard D, Besse B. A Long-Term Spinal Intramedullary Response to Ceritinib in ALK Rearranged Non-Small-Cell Lung Cancer. J Thorac Oncol. 2015 Jun;10(6):e44-5. doi: 10.1097/JTO.0000000000000501. PubMed PMID: 26001149.
3: Correction: ceritinib for the treatment of late-stage (metastatic) non-small cell lung cancer. Clin Cancer Res. 2015 May 15;21(10):2412. doi: 10.1158/1078-0432.CCR-15-0482. PubMed PMID: 25979933.
4: Kanaan Z, Kloecker GH, Paintal A, Perez CA. Novel targeted therapies for resistant ALK-rearranged non-small-cell lung cancer: ceritinib and beyond. Onco Targets Ther. 2015 Apr 20;8:885-92. doi: 10.2147/OTT.S67262. eCollection 2015. Review. PubMed PMID: 25945060; PubMed Central PMCID: PMC4408973.
5: Rothschild SI. Ceritinib-a second-generation ALK inhibitor overcoming resistance in ALK-rearranged non-small cell lung cancer. Transl Lung Cancer Res. 2014 Dec;3(6):379-81. doi: 10.3978/j.issn.2218-6751.2014.11.09. PubMed PMID: 25806326; PubMed Central PMCID: PMC4367664.
6: Ceccon M. Ceritinib as a promising therapy for ALK related diseases. Transl Lung Cancer Res. 2014 Dec;3(6):376-8. doi: 10.3978/j.issn.2218-6751.2014.08.09. PubMed PMID: 25806325; PubMed Central PMCID: PMC4367665.
7: Khozin S, Blumenthal GM, Zhang L, Tang S, Brower M, Fox E, Helms W, Leong R, Song P, Pan Y, Liu Q, Zhao P, Zhao H, Lu D, Tang Z, Al Hakim A, Boyd K, Keegan P, Justice R, Pazdur R. FDA approval: ceritinib for the treatment of metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer. Clin Cancer Res. 2015 Jun 1;21(11):2436-9. doi: 10.1158/1078-0432.CCR-14-3157. Epub 2015 Mar 9. PubMed PMID: 25754348.
8: Lanshoeft C, Heudi O, Raccuglia M, Leuthold LA, Picard F, Kretz O. Ultrafast quantitative MS-based method for ceritinib analysis in human plasma samples from clinical trial. Bioanalysis. 2015 Mar;7(4):425-35. doi: 10.4155/bio.14.292. PubMed PMID: 25747762.
9: Ou SH, Greenbowe J, Khan ZU, Azada MC, Ross JS, Stevens PJ, Ali SM, Miller VA, Gitlitz B. I1171 missense mutation (particularly I1171N) is a common resistance mutation in ALK-positive NSCLC patients who have progressive disease while on alectinib and is sensitive to ceritinib. Lung Cancer. 2015 May;88(2):231-4. doi: 10.1016/j.lungcan.2015.02.005. Epub 2015 Feb 12. PubMed PMID: 25736571.
10: Gainor JF, Tan DS, De Pas T, Solomon BJ, Ahmad A, Lazzari C, de Marinis F, Spitaleri G, Schultz K, Friboulet L, Yeap BY, Engelman JA, Shaw AT. Progression-Free and Overall Survival in ALK-Positive NSCLC Patients Treated with Sequential Crizotinib and Ceritinib. Clin Cancer Res. 2015 Feb 27. [Epub ahead of print] PubMed PMID: 25724526.