Ceritinib free base
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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.


Chemical Structure

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Ceritinib free base
CAS# 1032900-25-6 (free base)

Theoretical Analysis

MedKoo Cat#: 205511
Name: Ceritinib free base
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

Price and Availability

Size Price Availability Quantity
25.0mg USD 110.0 Ready to ship
50.0mg USD 150.0 Ready to ship
100.0mg USD 250.0 Ready to ship
200.0mg USD 450.0 Ready to ship
500.0mg USD 650.0 Ready to ship
1.0g USD 950.0 Ready to ship
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Related CAS #: 1032900-25-6 (free base)   1380575-43-8 (2HCl)   1190399-48-4 (xHCl)   2055376-76-4 (tosylate)   2055376-74-2 (mesylate)    

Synonym: LDK-378; LDK378; LDK 378; 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

Appearance: white 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, not in water

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: 2934.99.9001

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 2.79 5.0

Preparing Stock Solutions

The following data is based on the product molecular weight 558.14 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
Formulation 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 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: Ignatius Ou SH, Nishio M, Ahn MJ, Mok T, Barlesi F, Zhou C, Felip E, de Marinis F, Kim SW, Pérol M, Liu G, Migliorino MR, Kim DW, Novello S, Bearz A, Garrido P, Mazieres J, Morabito A, Lin HM, Yang H, Niu H, Zhang P, Kim ES. Efficacy of Brigatinib in Patients With Advanced Anaplastic Lymphoma Kinase- Positive Non-Small Cell Lung Cancer Who Progressed on Alectinib or Ceritinib: ALTA-2 Study. J Thorac Oncol. 2022 Sep 9:S1556-0864(22)01584-2. doi: 10.1016/j.jtho.2022.08.018. Epub ahead of print. PMID: 36096442.

2: Fang L, Ding G, Wang M, Ye Y, Yan X, Ding P, Wang J, Zhang Y. Excellent response of lung adenocarcinoma harboring a rare SLC8A1 downstream intergenic region ALK fusion to ceritinib treatment: A case report. Medicine (Baltimore). 2022 Aug 26;101(34):e30255. doi: 10.1097/MD.0000000000030255. PMID: 36042596; PMCID: PMC9410632.

3: Schäkel L, Mirza S, Winzer R, Lopez V, Idris R, Al-Hroub H, Pelletier J, Sévigny J, Tolosa E, Müller CE. Protein kinase inhibitor ceritinib blocks ectonucleotidase CD39 - a promising target for cancer immunotherapy. J Immunother Cancer. 2022 Aug;10(8):e004660. doi: 10.1136/jitc-2022-004660. PMID: 35981785; PMCID: PMC9394215.

4: Li H, Deng Y, Chen B, Xiao Y, Yang J, Liu Q, Lin G. Identification of a novel RMST-ALK rearrangement in advanced lung adenocarcinoma and durable response to ceritinib: A case report. Front Oncol. 2022 Aug 1;12:913838. doi: 10.3389/fonc.2022.913838. PMID: 35978810; PMCID: PMC9376587.

5: Mai S, Wang Y, Wang X, Yang W, Gao H, Xu Z, Xu L, Xu L, Ou Q, Chen H, Wang Z. Neoadjuvant ceritinib treatment in ALK-rearranged locally advanced adenosquamous carcinoma: A case report. Thorac Cancer. 2022 Aug;13(15):2275-2278. doi: 10.1111/1759-7714.14558. Epub 2022 Jul 12. PMID: 35818908; PMCID: PMC9346166.

6: Dong S, Yousefi H, Savage IV, Okpechi SC, Wright MK, Matossian MD, Collins- Burow BM, Burow ME, Alahari SK. Ceritinib is a novel triple negative breast cancer therapeutic agent. Mol Cancer. 2022 Jun 29;21(1):138. doi: 10.1186/s12943-022-01601-0. PMID: 35768871; PMCID: PMC9241294.

7: Su CT, Wu JH. Management of Combined Therapy (Ceritinib, A. cinnamomea, G. lucidum, and Photobiomodulation) in Advanced Non- Small-Cell Lung Cancer: A Case Report. Life (Basel). 2022 Jun 9;12(6):862. doi: 10.3390/life12060862. PMID: 35743893; PMCID: PMC9228003.

8: Liao J, Guan H, Yu M, Zhou P, Han Y, Peng X, Zhang S. Pulmonary granulomatous inflammation after ceritinib treatment in advanced ALK-rearranged pulmonary adenocarcinoma. Invest New Drugs. 2022 Oct;40(5):1141-1145. doi: 10.1007/s10637-022-01270-2. Epub 2022 Jun 21. PMID: 35727390; PMCID: PMC9395502.

9: Qiu Z, Xian X, Liu C, Yu M, Lin F, Huang M, Wang K. Clinical data from the real world: Efficacy analysis of ceritinib (450mg) in ALK-rearrangement non- small-cell lung cancer patients with brain metastases in China. J Cancer Res Ther. 2022 Apr;18(2):516-524. doi: 10.4103/jcrt.jcrt_1453_21. PMID: 35645123.

10: Cho BC, Kim DW, Batra U, Park K, Kim SW, Yang CT, Voon PJ, Sriuranpong V, Babu KG, Amin K, Wang Y, Sen P, Slimane K, Geater S. Efficacy and Safety of Ceritinib 450 mg/d With Food and 750 mg/d in Fasted State in Treatment-Naïve Patients With ALK+ Non-small Cell Lung Cancer: Results From the ASCEND-8 Asian Subgroup Analysis. Cancer Res Treat. 2022 Mar 25. doi: 10.4143/crt.2021.1571. Epub ahead of print. PMID: 35344649.

11: Santoro A, Su WC, Navarro A, Simonelli M, Ch Yang J, Ardizzoni A, Barlesi F, Hyoung Kang J, DiDominick S, Abdelhady A, Chen X, Stammberger U, Felip E. Phase Ib/II study of ceritinib in combination with ribociclib in patients with ALK- rearranged non-small cell lung cancer. Lung Cancer. 2022 Apr;166:170-177. doi: 10.1016/j.lungcan.2022.02.010. Epub 2022 Mar 1. PMID: 35298959.

12: An Liquid Chromatography-Tandem Mass Spectrometry Method for the Simultaneous Determination of Afatinib, Alectinib, Ceritinib, Crizotinib, Dacomitinib, Erlotinib, Gefitinib, and Osimertinib in Human Serum: Erratum. Ther Drug Monit. 2022 Apr 1;44(2):357. doi: 10.1097/FTD.0000000000000958. Erratum for: Ther Drug Monit. 2021 Dec 1;43(6):772-779. PMID: 35292612.

13: Gao P, Tang K, Hao Y, Li W, Lv X, Li D, Jia Y. Case Report: Patient With Lung Adenocarcinoma With ALK-HLA-DRB1 Rearrangement Shows Impressive Progression-Free Survival After Sequential Crizotinib and Ceritinib Treatment. Front Oncol. 2022 Feb 25;12:762338. doi: 10.3389/fonc.2022.762338. PMID: 35280798; PMCID: PMC8914946.

14: Chow LQM, Barlesi F, Bertino EM, van den Bent MJ, Wakelee HA, Wen PY, Chiu CH, Orlov S, Chiari R, Majem M, McKeage M, Yu CJ, Garrido P, Hurtado FK, Arratia PC, Song Y, Branle F, Shi M, Kim DW. ASCEND-7: Efficacy and Safety of Ceritinib Treatment in Patients with ALK-Positive Non-Small Cell Lung Cancer Metastatic to the Brain and/or Leptomeninges. Clin Cancer Res. 2022 Jun 13;28(12):2506-2516. doi: 10.1158/1078-0432.CCR-21-1838. PMID: 35091443.

15: Shen J, Meng Y, Wang K, Gao M, Du J, Wang J, Li Z, Zuo D, Wu Y. EML4-ALK G1202R mutation induces EMT and confers resistance to ceritinib in NSCLC cells via activation of STAT3/Slug signaling. Cell Signal. 2022 Apr;92:110264. doi: 10.1016/j.cellsig.2022.110264. Epub 2022 Jan 24. PMID: 35085771.

16: Shen G, Du Y, Shen J, Zhang J, Xia X, Huang M, Shen W. Clinical Impact of Switching to Ceritinib After Severe AEs Related to Crizotinib/Alectinib in a Novel PTH2R-ALK Fusion Lung Adenocarcinoma: A Case Report. Onco Targets Ther. 2021 Dec 23;14:5471-5475. doi: 10.2147/OTT.S340984. PMID: 34992382; PMCID: PMC8711735.

17: Tan DS, Thomas M, Kim DW, Szpakowski S, Urban P, Mehra R, Chow LQM, Sharma S, Solomon BJ, Felip E, Camidge DR, Vansteenkiste J, Petruzzelli L, Pantano S, Shaw AT. Genetic landscape of patients with ALK-rearranged non-small-cell lung cancer (NSCLC) and response to ceritinib in ASCEND-1 study. Lung Cancer. 2022 Jan;163:7-13. doi: 10.1016/j.lungcan.2021.11.007. Epub 2021 Nov 20. PMID: 34890832.

18: Mittal A, Gupta A, Rastogi S, Barwad A, Sharma S. Erratum: Near-complete response to low-dose ceritinib in recurrent infantile inflammatory myofibroblastic tumour. Ecancermedicalscience. 2021 Sep 13;15:1286. doi: 10.3332/ecancer.2021.1286. Erratum for: Ecancermedicalscience. 15:1. PMID: 34824609; PMCID: PMC8580590.

19: Kanakkanthara A, Hou X, Ekstrom TL, Zanfagnin V, Huehls AM, Kelly RL, Ding H, Larson MC, Vasmatzis G, Oberg AL, Kaufmann SH, Mansfield AS, Weroha SJ, Karnitz LM. Repurposing Ceritinib Induces DNA Damage and Enhances PARP Inhibitor Responses in High-Grade Serous Ovarian Carcinoma. Cancer Res. 2022 Jan 15;82(2):307-319. doi: 10.1158/0008-5472.CAN-21-0732. Epub 2021 Nov 22. PMID: 34810199; PMCID: PMC8770599.

20: Fischer M, Moreno L, Ziegler DS, Marshall LV, Zwaan CM, Irwin MS, Casanova M, Sabado C, Wulff B, Stegert M, Wang L, Hurtado FK, Branle F, Geoerger B, Schulte JH. Ceritinib in paediatric patients with anaplastic lymphoma kinase- positive malignancies: an open-label, multicentre, phase 1, dose-escalation and dose-expansion study. Lancet Oncol. 2021 Dec;22(12):1764-1776. doi: 10.1016/S1470-2045(21)00536-2. Epub 2021 Nov 12. PMID: 34780709.



Additional Information

Related:
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.