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LDK378

Cat. No. M2075
LDK378 Structure
Size Price Availability Quantity
10mg USD 70 In stock
100mg USD 230 In stock
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Quality Control
Biological Activity

LDK378 is a selective small molecule inhibitor of ALK, a target found in metastatic non-small cell lung cancer (NSCLC). 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. LDK378 induces a dose-dependent growth inhibition and tumor regression in the Karpas299 and H2228 rat xenograft models, with no body-weight loss. 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 who had progressed during or after crizotinib therapy or had not been previously treated with crizotinib.

Protocol
Cell Experiment
Cell lines Ba/F3-NPM-ALK, Ba/F3-Tel-InsR, Ba/F3-WT, Karpas299 cells
Preparation 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.
Concentrations ~100 μM
Incubation time 2-3 days
Animal Experiment
Animal models RNU nude rats bearing the Karpas299/H2228 tumors
Formulation LDK378 (phosphate salt) formulated in 0.5% methylcellulose/0.5% Tween 80
Dosages ~50 mg/kg
Administration Oral gavage
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 558.14
Formula C28H36ClN5O3S
CAS Number 1032900-25-6
Purity 98.78%
Solubility DMSO 90 mg/mL
Ethanol 30 mg/mL
Storage at -20°C
References

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.
Marsilje TH, et al. J Med Chem. 2013 Jun 26. PMID: 23742252.

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Crizotinib hydrochloride

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Brigatinib

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ALK-IN-1

ALK-IN-1 is an analog of AP26113 which is a potent and selective ALK inhibitor. It is also an inhibitor of EGFR.

  Catalog
Abmole Inhibitor Catalog 2017




Keywords: LDK378 supplier, ALK, inhibitors

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