| Size | Price | Stock | Qty |
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| 5mg |
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| 25mg |
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| 100mg |
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| 250mg |
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| 500mg |
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Purity: =99.62%
Ceritinib (formerly known as LDK378; trade name: Zykadia) is novel, potent and selective inhibitor against ALK (anaplastic lymphoma kinase positive) with potential anticancer activity. In cell-free experiments, it inhibits ALK with an IC50 of 0.2 nM and exhibits 40- and 35-fold selectivity for ALK over IGF-1R and InsR, respectively. The FDA approved ceritinib in April 2014 as a treatment for non-small cell lung cancer (NSCLC). In 78 patients with anaplastic ALK+ metastatic non-small cell lung cancer who had either not received crizotinib therapy before or had progressed during the course of crizotinib therapy, Ceritinib demonstrated a significant clinical response in Phase I trials.
| Targets |
ALK (IC50 = 0.2 nM); InsR (IC50 = 7 nM); IGF-1R (IC50 = 8 nM); STK22D (IC50 = 23 nM); FLT3 (IC50 = 60 nM); FGFR2 (IC50 = 260 nM)
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| ln Vitro |
LDK378 has a much stronger anti-proliferative effect in Ba/F3-NPM-ALK and Karpas290 cells, with IC50 values of 26.0 nM and 22.8 nM, respectively, than in Ba/F3-Tel-InsR and Ba/F3-WT cells, where the values are 319.5 nM and 2477 nM.[1]
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| ln Vivo |
LDK378 exhibits negligible levels of glutathione (GSH) adducts (<1%) in liver microsomes and is intended to lessen the likelihood of reactive metabolites forming. With moderate inhibition of CYP3A4 (midazolam substrate) and hERG, LDK378 exhibits a relatively good metabolic stability. When compared to liver blood flow, LDK378 shows poor plasma clearance in mice, rats, dogs, and monkeys. However, in these animals, oral bioavailability is greater than 55%. With no reduction in body weight, LDK378 causes a dose-dependent growth inhibition and tumor regression in the rat xenograft models Karpas299 and H2228. When given chronically in mice at doses up to 100 mg/kg, LDK378 has no effect on insulin levels or plasma glucose utilization.
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| Enzyme Assay |
All kinases are expressed using the baculovirus expression technology as either GST- or histidine-tagged fusion proteins, with the exception of untagged ERK2, which is made in E. coli. Using the LabChip mobility shift assay, the kinase activity is determined. For sixty minutes, the assay is run at 30°C. It is routinely possible to determine the effect of LDK378 on the enzymatic activity from a single reading (end point measurement) by analyzing the linear progress curves in both the presence and absence of LDK378.
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| Cell Assay |
LDK378 or DMSO are serially diluted and incubated with luciferase-expressing cells for two to three days. Using the Bright-Glo Luciferase Assay System, luciferase expression is measured as a proxy for cell proliferation and survival. The XLFit program is used to generate IC50 values.
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| Animal Protocol |
Studies on in vivo PK are carried out on dogs, rats, mice, and cynomolgus monkeys. Male Balb/c mice are given cetinib (LDK378) (HCl salt) orally via gavage at a dose of 20 mg/kg (n=3) and intravenously via tail vein at a dose of 5 mg/kg (n= 3). Sprague-Dawley rats are dosed with Ceritinib (LDK378) (HCl salt) intravenously via the tail vein at 3 mg/kg (n=3) and orally via gavage at 10 mg/kg (n=3) using the same formulation. Serial blood samples are taken over the course of 24 hours following dosage at prearranged times. Ceritinib (phosphate salt) is given as a single intravenous (n = 2) or oral (n = 3) dose to male beagle dogs. The intravenous solution has a dosage of 5 mg/kg, while the oral suspension has a dosage of 20 mg/kg. A single intravenous (n = 2) or oral (n = 3) dose of Ceritinib (free base) is given to male Cynomologus monkeys. The intravenous solution has a dose of 5 mg/kg, while the oral suspension has a dose of 60 mg/kg. For plasma, blood is drawn at prearranged intervals over a period of 144 hours following dosage.
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| References |
| Molecular Formula |
C28H36CLN5O3S
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|---|---|
| Molecular Weight |
558.14
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| Exact Mass |
557.22
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| Elemental Analysis |
C, 60.25; H, 6.50; Cl, 6.35; N, 12.55; O, 8.60; S, 5.75
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| CAS # |
1032900-25-6
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| Related CAS # |
Ceritinib dihydrochloride;1380575-43-8;Ceritinib-d7;1632484-77-5
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| Appearance |
white solid powder
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| SMILES |
CC1=CC(=C(C=C1C2CCNCC2)OC(C)C)NC3=NC=C(C(=N3)NC4=CC=CC=C4S(=O)(=O)C(C)C)Cl
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| InChi Key |
VERWOWGGCGHDQE-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
5-chloro-2-N-(5-methyl-4-piperidin-4-yl-2-propan-2-yloxyphenyl)-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine
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| Synonyms |
LDK 378; Ceritinib; LDK378; LDK-378; trade name: Zykadia
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.5 mg/mL (0.90 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.5 mg/mL (0.90 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 0.5 mg/mL (0.90 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 1% DMSO+30% polyethylene glycol+1% Tween 80: 30 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7917 mL | 8.9583 mL | 17.9167 mL | |
| 5 mM | 0.3583 mL | 1.7917 mL | 3.5833 mL | |
| 10 mM | 0.1792 mL | 0.8958 mL | 1.7917 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03501368 | Active Recruiting |
Drug: Ceritinib Drug: Trametinib |
Melanoma Advanced Melanoma |
H. Lee Moffitt Cancer Center and Research Institute |
June 27, 2018 | Phase 1 |
| NCT02321501 | Active Recruiting |
Drug: Ceritinib Drug: Everolimus |
ALK Positive ROS1 Gene Rearrangement |
M.D. Anderson Cancer Center | June 22, 2016 | Phase 1 |
| NCT03611738 | Active Recruiting |
Drug: Ceritinib Drug: Docetaxel |
Lung Cancer | H. Lee Moffitt Cancer Center and Research Institute |
February 1, 2019 | Phase 1 |
| NCT01828099 | Active Recruiting |
Drug: Ceritinib Drug: Pemetrexed |
Non-Small Cell Lung Cancer/td> | Novartis Pharmaceuticals | July 9, 2013 | Phase 3 |
| NCT02584933 | Recruiting | Drug: ceritinib | ALK Positive Malignancies | Novartis Pharmaceuticals | December 11, 2015 | Phase 4 |
Dose–response and time course comparison of ALK inhibition by crizotinib or ceritinib.Mol Oncol.2017 Aug;11(8):996-1006. |
Tumor volume measurement and MSD®immunoassay quantitation of Th‐ALKF1174L/MYCNtumors following the treatment with crizotinib or ceritinib. Tumor‐bearing animals were treated with either crizotinib (100mg·kg−1per day, orally) or ceritinib (100mg·kg−1per day, orally) for 7days before animal sacrifice and harvesting of tumor tissue samples. |
Basal ALK activity in neuroblastoma cell lines. (A) Immunoblots of lysates from neuroblastoma cell line panel, including lysate from Ba/F3ALK F1174Las a positive control for ALK expression and lysate from Hela cells as negative control for ALK expression.Mol Oncol.2017 Aug;11(8):996-1006. |
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