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LDK378 dihydrochloride

Cat. No. M6168
LDK378 dihydrochloride Structure
Synonym:

Ceritinib dihydrochloride

Size Price Availability Quantity
Free Sample (0.5-1 mg)  USD 0 In stock
10mg USD 70 In stock
50mg USD 100 In stock
100mg USD 180 In stock
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Quality Control
Biological Activity

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.

In vivio: 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.

Protocol
Cell Experiment
Cell lines KB and KBv200 cells
Preparation method KB and KBv200 cells were treated with 10 μM DOX for 3 h at 37°C, then the cells were washed three times and subsequently maintained at 37°C with culture media without DOX in the presence or absence of 0.5 μM ceritinib at 0, 15, 30, 60 and 120 min, cells were collected and washed three times with ice-cold PBS.
Concentrations 0.5 μM
Incubation time 15, 30, 60 and 120 min
Animal Experiment
Animal models Athymic nude mice
Formulation saline
Dosages 25 mg/kg
Administration p.o.
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 631.06
Formula C28H38Cl3N5O3S
CAS Number 1380575-43-8
Purity 99.81%
Solubility 170 mg/mL in water
Storage at -20°C
References

Effect of ceritinib (LDK378) on enhancement of chemotherapeutic agents in ABCB1 and ABCG2 overexpressing cells in vitro and in vivo.
Hu J, et al. Oncotarget. 2015 Dec 29;6(42):44643-59. PMID: 26556876.

LDK378: a promising anaplastic lymphoma kinase (ALK) inhibitor.
Chen J, et al. J Med Chem. 2013 Jul 25;56(14):5673-4. PMID: 23837797.

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  Catalog
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Keywords: LDK378 dihydrochloride, Ceritinib dihydrochloride supplier, ALK, inhibitors

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