Ceritinib HCl
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MedKoo CAT#: 123125

CAS#: 1380575-43-8 (2HCl)

Description: Ceritinib, also known as LDK-378, 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.


Chemical Structure

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Ceritinib HCl
CAS# 1380575-43-8 (2HCl)

Theoretical Analysis

MedKoo Cat#: 123125
Name: Ceritinib HCl
CAS#: 1380575-43-8 (2HCl)
Chemical Formula: C28H38Cl3N5O3S
Exact Mass:
Molecular Weight: 631.054
Elemental Analysis: C, 53.29; H, 6.07; Cl, 16.85; N, 11.10; O, 7.61; S, 5.08

Price and Availability

Size Price Availability Quantity
1.0g USD 1850.0 2 Weeks
2.0g USD 2750.0 2 Weeks
5.0g USD 3850.0 2 Weeks
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Related CAS #: 1032900-25-6 (free base)   1380575-43-8 (2HCl)   1190399-48-4 (xHCl)    

Synonym: LDK-378; LDK 378; LDK378; Ceritinib HCl; Ceritinib dihydrochloride

IUPAC/Chemical Name: 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine dihydrochloride

InChi Key: WNCJOPLFICTLPT-UHFFFAOYSA-N

InChi Code: InChI=1S/C28H36ClN5O3S.2ClH/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);2*1H

SMILES Code: O=S(C1=CC=CC=C1NC2=NC(NC3=CC(C)=C(C4CCNCC4)C=C3OC(C)C)=NC=C2Cl)(C(C)C)=O.[H]Cl.[H]Cl

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.03.00

Product Data:

Biological target: Ceritinib (LDK378) is a selective, ATP-competitive ALK tyrosine kinase inhibitor with an IC50 of 200 pM.
In vitro activity: Interrogation of in vitro models of acquired resistance to crizotinib, including cell lines established from biopsies of crizotinib-resistant NSCLC patients, revealed that ceritinib potently overcomes crizotinib resistance mutations. In particular, ceritinib effectively inhibits ALK harboring L1196M, G1269A, I1171T and S1206Y mutations, and a co-crystal of ceritinib bound to ALK provides structural bases for this increased potency. However, ceritinib did not overcome two crizotinib-resistant ALK mutations, G1202R and F1174C. Reference: Cancer Discov. 2014 Jun;4(6):662-673. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068971/
In vivo activity: The efficacy of ceritinib was tested against crizotinib-resistant H2228 xenograft tumor models as well as one of the resistance models that did not harbor a resistance mutation nor ALK amplification. While each was resistant to crizotinib at 100 mg/kg, ceritinib suppressed tumor growth in multiple resistance models (Fig.5A, B, C and D). In the wild-type and I1171T resistant models, ceritinib demonstrated impressive anti-tumor activity, while it was less active in the C1156Y resistant model and was inactive against the G1202R resistant model. This data is consistent with the Ba/F3 models in which ceritinib was more potent against I1171T than the C1156Y and G1202R mutants (Fig. 4A). This data provides evidence that ceritinib can overcome resistance in vivo, especially in tumors harboring wild-type, L1196M or I1171T ALK fusion genes. Reference: Cancer Discov. 2014 Jun;4(6):662-673. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068971/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 100.0 158.46
Water 170.0 269.39

Preparing Stock Solutions

The following data is based on the product molecular weight 631.054 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
In vitro protocol: 1. Friboulet L, Li N, Katayama R, Lee CC, Gainor JF, Crystal AS, Michellys PY, Awad MM, Yanagitani N, Kim S, Pferdekamper AC, Li J, Kasibhatla S, Sun F, Sun X, Hua S, McNamara P, Mahmood S, Lockerman EL, Fujita N, Nishio M, Harris JL, Shaw AT, Engelman JA. The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer. Cancer Discov. 2014 Jun;4(6):662-673. doi: 10.1158/2159-8290.CD-13-0846. Epub 2014 Mar 27. PMID: 24675041; PMCID: PMC4068971.
In vivo protocol: 1. Friboulet L, Li N, Katayama R, Lee CC, Gainor JF, Crystal AS, Michellys PY, Awad MM, Yanagitani N, Kim S, Pferdekamper AC, Li J, Kasibhatla S, Sun F, Sun X, Hua S, McNamara P, Mahmood S, Lockerman EL, Fujita N, Nishio M, Harris JL, Shaw AT, Engelman JA. The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer. Cancer Discov. 2014 Jun;4(6):662-673. doi: 10.1158/2159-8290.CD-13-0846. Epub 2014 Mar 27. PMID: 24675041; PMCID: PMC4068971.

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1: Institute for Quality and Efficiency in Health Care. Ceritinib -- Benefit Assessment According to §35a Social Code Book V [Internet]. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2015 Sep 29. Available from http://www.ncbi.nlm.nih.gov/books/NBK458396/ PubMed PMID: 29144697.

2: Califano R, Greystoke A, Lal R, Thompson J, Popat S. Management of ceritinib therapy and adverse events in patients with ALK-rearranged non-small cell lung cancer. Lung Cancer. 2017 Sep;111:51-58. doi: 10.1016/j.lungcan.2017.06.004. Epub 2017 Jun 9. Review. PubMed PMID: 28838397.

3: Santarpia M, Daffinà MG, D'Aveni A, Marabello G, Liguori A, Giovannetti E, Karachaliou N, Gonzalez Cao M, Rosell R, Altavilla G. Spotlight on ceritinib in the treatment of ALK+ NSCLC: design, development and place in therapy. Drug Des Devel Ther. 2017 Jul 5;11:2047-2063. doi: 10.2147/DDDT.S113500. eCollection 2017. Review. PubMed PMID: 28740365; PubMed Central PMCID: PMC5503498.

4: Ceritinib for non-small cell lung cancer. Aust Prescr. 2017 Apr;40(2):82-83. doi: 10.18773/austprescr.2017.020. Epub 2017 Apr 3. Review. PubMed PMID: 28507404; PubMed Central PMCID: PMC5407992.

5: Mok TSK, Crino L, Felip E, Salgia R, De Pas T, Tan DSW, Chow LQM. The accelerated path of ceritinib: Translating pre-clinical development into clinical efficacy. Cancer Treat Rev. 2017 Apr;55:181-189. doi: 10.1016/j.ctrv.2017.03.006. Epub 2017 Mar 30. Review. PubMed PMID: 28427013.

6: Deeks ED. Ceritinib: a Review in ALK-Positive Advanced NSCLC. Target Oncol. 2016 Oct;11(5):693-700. Review. PubMed PMID: 27699584.

7: Rothschild SI. New treatment options for ALK+ advanced non-small-cell lung cancer: critical appraisal of ceritinib. Ther Clin Risk Manag. 2016 May 5;12:735-41. doi: 10.2147/TCRM.S87876. eCollection 2016. Review. PubMed PMID: 27217763; PubMed Central PMCID: PMC4863587.

8: Muller IB, De Langen AJ, Honeywell RJ, Giovannetti E, Peters GJ. Overcoming crizotinib resistance in ALK-rearranged NSCLC with the second-generation ALK-inhibitor ceritinib. Expert Rev Anticancer Ther. 2016;16(2):147-57. doi: 10.1586/14737140.2016.1131612. Epub 2016 Jan 4. Review. PubMed PMID: 26654422.

9: Nix NM, Brown KS. Ceritinib for ALK-Rearrangement-Positive Non-Small Cell Lung Cancer. J Adv Pract Oncol. 2015 Mar-Apr;6(2):156-60. Epub 2015 Mar 1. Review. PubMed PMID: 26649248; PubMed Central PMCID: PMC4601895.

10: El-Osta H, Shackelford R. Personalized treatment options for ALK-positive metastatic non-small-cell lung cancer: potential role for Ceritinib. Pharmgenomics Pers Med. 2015 Sep 29;8:145-54. doi: 10.2147/PGPM.S71100. eCollection 2015. Review. PubMed PMID: 26622190; PubMed Central PMCID: PMC4638315.

11: Giroux Leprieur E, Fallet V, Wislez M. [Modalities of use of ceritinib (Zykadia™), a 2nd generation ALK inhibitor, in advanced stage non-small cell lung cancer]. Bull Cancer. 2015 Dec;102(12):1053-7. doi: 10.1016/j.bulcan.2015.09.007. Epub 2015 Nov 18. Review. French. PubMed PMID: 26597476.

12: Landi L, Cappuzzo F. Ceritinib for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer. Expert Rev Clin Pharmacol. 2016;9(2):203-14. doi: 10.1586/17512433.2016.1122518. Epub 2015 Dec 16. Review. PubMed PMID: 26582431.

13: Kaczmar J, Mehra R. The efficacy of ceritinib in patients with ALK-positive non-small cell lung cancer. Ther Adv Respir Dis. 2015 Oct;9(5):236-41. doi: 10.1177/1753465815597834. Epub 2015 Jul 30. Review. PubMed PMID: 26229087.

14: Burns MW, Kim ES. Profile of ceritinib in the treatment of ALK+ metastatic non-small-cell lung cancer. Lung Cancer (Auckl). 2015 May 15;6:35-42. doi: 10.2147/LCTT.S69114. eCollection 2015. Review. PubMed PMID: 28210149; PubMed Central PMCID: PMC5217515.

15: 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.

16: Massarelli E, Papadimitrakopoulou V. Ceritinib for the treatment of late-stage (metastatic) non-small cell lung cancer. Clin Cancer Res. 2015 Feb 15;21(4):670-4. doi: 10.1158/1078-0432.CCR-14-1291. Epub 2015 Jan 6. Review. Erratum in: Clin Cancer Res. 2015 May 15;21(10):2412. PubMed PMID: 25564153.

17: Li S, Qi X, Huang Y, Liu D, Zhou F, Zhou C. Ceritinib (LDK378): a potent alternative to crizotinib for ALK-rearranged non-small-cell lung cancer. Clin Lung Cancer. 2015 Mar;16(2):86-91. doi: 10.1016/j.cllc.2014.09.011. Epub 2014 Oct 13. Review. PubMed PMID: 25458559.

18: Cooper MR, Chim H, Chan H, Durand C. Ceritinib: a new tyrosine kinase inhibitor for non-small-cell lung cancer. Ann Pharmacother. 2015 Jan;49(1):107-12. doi: 10.1177/1060028014553619. Epub 2014 Sep 25. Review. PubMed PMID: 25258420.

19: Landi L, Cappuzzo F. Ceritinib for the treatment of non-small cell lung cancer. Drugs Today (Barc). 2014 Jul;50(7):465-73. doi: 10.1358/dot.2014.50.7.2133568. Review. PubMed PMID: 25101329.

20: Dhillon S, Clark M. Ceritinib: first global approval. Drugs. 2014 Jul;74(11):1285-91. doi: 10.1007/s40265-014-0251-3. Review. PubMed PMID: 24980964.