LDK378 (Synonyms: LDK 378;LDK-378;Ceritinib) |
| Catalog No.GC14552 |
LDK378 (LDK378) is a selective, orally bioavailable, and ATP-competitive ALK tyrosine kinase inhibitor with an IC50 of 200 pM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1032900-25-6
Sample solution is provided at 25 µL, 10mM.
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LDK378 is a highly potent inhibitor of anaplastic lymphoma kinase (ALK), which is a receptor tyrosine kinase belonging to the superfamily of insulin receptor, with half maximal inhibitory concentration IC50 of 200 pM. LDK378 also exhibits modest to high inhibition against a panel of other kinases, in which only three kinases with IC50 below 100 nM includes IGF-1R (8 nM), InsR (7 nM) and STK22D (23 nM). In previous studies, LDK378 has been found to inhibit the proliferation of Ba/F3 cells transfected with the NPM-ALK fusion gene and Karpas 299 human non-Hodgkin’s Ki-positivr large cell lymphoma harboring the NPM-ALK fusion gene with IC50 of 22.8 nM and 26 nM.
References:
[1]Chen J, Jiang C, Wang S. LDK378: a promising anaplastic lymphoma kinase (ALK) inhibitor. J Med Chem. 2013 Jul 25;56(14):5673-4. doi: 10.1021/jm401005u. Epub 2013 Jul 9.
[2]Marsilje TH, Pei W, Chen B, Lu W, Uno T, Jin Y, Jiang T, Kim S, Li N, Warmuth M, Sarkisova Y, Sun F, Steffy A, Pferdekamper AC, Li AG, Joseph SB, Kim Y, Liu B, Tuntland T, Cui X, Gray NS, Steensma R, Wan Y, Jiang J, Chopiuk G, Li J, Gordon WP, Richmond W, Johnson K, Chang J, Groessl T, He YQ, Phimister A, Aycinena A, Lee CC, Bursulaya B, Karanewsky DS, Seidel HM, Harris JL, Michellys PY. Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials. J Med Chem. 2013 Jul 25;56(14):5675-90. doi: 10.1021/jm400402q. Epub 2013 Jun 26.
| Cell experiment [1]: | |
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Cell lines |
The murine pro-B cell line Ba/F3, human cell line Karpas290 |
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Preparation method |
The solubility of this compound in DMSO is >14mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
10 to 50 nM |
|
Applications |
LDK378 showed great anti-proliferative activity in Ba/F3-NPM-ALK and Karpas290 cells. |
| Animal experiment [2]: | |
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Animal models |
2-week Karpas299 (sc injection of Karpas299 cells possessing the NPM-ALK fusion) and H2228 (sc injection of H2228 cells possessing the EML4-ALK fusion) rat xenograft models |
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Dosage form |
6.25, 12.5, 25, 50 mg/kg; every day for 14 consecutive days |
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Application |
In the Karpas299 study, LDK378 induced a dose-dependent growth inhibition and tumor regression. In the H2228 study, LDK378 induced a dose-dependent growth inhibition and complete tumor regression at 25mg/kg. In both models, LDK378 was well tolerated and no body weight loss was observed at all doses tested. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Marsilje TH., et al. Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4- (2-(isopropylsulfonyl)phenyl)pyrimidine -2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials. J Med Chem. 2013, Jun 6. |
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| Cas No. | 1032900-25-6 | SDF | |
| Synonyms | LDK 378;LDK-378;Ceritinib | ||
| 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 | ||
| Canonical SMILES | CC1=CC(=C(C=C1C2CCNCC2)OC(C)C)NC3=NC=C(C(=N3)NC4=CC=CC=C4S(=O)(=O)C(C)C)Cl | ||
| Formula | C28H36ClN5O3S | M.Wt | 558.14 |
| Solubility | DMSO : 5.6 mg/mL (10.03 mM; Need ultrasonic) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 28 reference(s) in Google Scholar.)
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