Antibodies
LDK378
- 貨號 Cat. No.
- S7083
- 規格 Size
- 5mgã€50 mg
- 品牌 Brand
- Selleckchem
Description
LDK378
Catalog No.S7083
LDK378 is potent inhibitor against ALK with IC50 of 0.2 nM, shows 40- and 35-fold selectivity against IGF-1R and InsR, respectively. Phase 2.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | LDK378 is potent inhibitor against ALK with IC50 of 0.2 nM, shows 40- and 35-fold selectivity against IGF-1R and InsR, respectively. Phase 2. | |||||
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| Targets | ALK | |||||
| IC50 | 0.2 nM [1] | |||||
| In vitro | LDK378 shows great anti-proliferative activity in Ba/F3-NPM-ALK and Karpas290 cells with IC50 of 26.0 nM and 22.8 nM, compared with IC50 of 319.5 nM and 2477 nM in Ba/F3-Tel-InsR and Ba/F3-WT cells. [1] | |||||
| In vivo | LDK378 is designed to reduce the possibility of forming reactive metabolites and shows undetectable levels of glutathione (GSH) adducts (<1%) in liver microsomes. LDK378 has relatively good metabolic stability, with moderate CYP3A4 (Midazolam substrate) inhibition and hERG inhibition. LDK378 exhibits low plasma clearance in animals (mouse, rat, dog and monkey) compared to liver blood flow, with the oral bioavailability of above 55% in mouse, rat, dog and monkey. LDK378 induces a dose-dependent growth inhibition and tumor regression in the Karpas299 and H2228 rat xenograft models, with no body-weight loss. LDK378 shows no impact on insulin levels or plasma glucose utilization in the mouse upon chronic dosing up to 100 mg/kg. [1] | |||||
| Features | Does not cross react with c-Met, and has an improved in vivo glucose homeostasis profile relative to TAE684. May be active in Crizotinib-relapsed tumors. | |||||
Protocol(Only for Reference)
Kinase Assay: [1]
| Enzymatic kinase profiling description | All kinases are expressed as either Histidine- or GST-tagged fusion proteins using the baculovirus expression technology except for the untagged ERK2 which is produced in E. coli. The kinase activity is measured in the LabChip mobility shift assay. The assay is performed at 30°C for 60 min. The effect of LDK378 on the enzymatic activity is obtained from the linear progress curves in the absence and presence of LDK378 and routinely determines from one reading (end point measurement) |
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Cell Assay: [1]
| Cell lines | Ba/F3-NPM-ALK, Ba/F3-Tel-InsR, Ba/F3-WT, Karpas299 cells |
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| Concentrations | ~100 μM |
| Incubation Time | 2-3 days |
| Method | Luciferase-expressing cells are incubated with serial dilutions of LDK378 or DMSO for 2-3 days. Luciferase expression is used as a measure of cell proliferation/survival and is evaluated with the Bright-Glo Luciferase Assay System. IC50 values are generated by using XLFit software. |
Animal Study: [1]
| Animal Models | RNU nude rats bearing the Karpas299/H2228 tumors |
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| Dosages | ~50 mg/kg |
| Administration | Oral gavage |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01685138 | Recruiting | Non-Small Cell Lung Cancer | Novartis|Novartis Pharmaceuticals | 2012-12 | Phase 2 |
| NCT01742286 | Recruiting | Anaplastic Lymphoma Kinase (ALK) | Novartis|Novartis Pharmaceuticals | 2013-03 | Phase 1 |
| NCT01772797 | Recruiting | Anaplastic Lymphoma Kinase (ALK)|Non-small Cell Lung Cancer | Novartis|Novartis Pharmaceuticals | 2013-06 | Phase 1 |
| NCT01828099 | Not yet recruiting | Non-Small Cell Lung Cancer | Novartis|Novartis Pharmaceuticals | 2013-06 | Phase 3 |
| NCT01828112 | Not yet recruiting | Non-Small Cell Lung Cancer | Novartis|Novartis Pharmaceuticals | 2013-06 | Phase 3 |
Chemical Information
| Molecular Weight (MW) | 558.14 |
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| Formula | C28H36ClN5O3S |
| CAS No. | 1032900-25-6 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 20 mg/mL heat (35 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | 3 mg/mL (5 mM) | ||
| * <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. | |||
| Chemical Name | 2,4-Pyrimidinediamine, 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]- |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
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| Mass(mg) | 0.55814 | 5.5814 | 11.1628 | 16.7442 |
