GSK1838705A_DataSheet_MedChemExpress

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Data Sheet

Product Name:Cat. No.:CAS No.:

Molecular Formula:Molecular Weight:Target:Pathway:Solubility:

GSK1838705AHY-130201116235-97-2C27H29FN8O3532.57

ALK; IGF–1R; Insulin Receptor

Protein Tyrosine Kinase/RTK; Protein Tyrosine Kinase/RTK; ProteinTyrosine Kinase/RTK10 mM in DMSO

BIOLOGICAL ACTIVITY: 

GSK1838705A is a potent small–molecule IGF–1R, the insulin receptor and anaplastic lymphoma kinase (ALK) inhibitor with IC50 of 2.0,1.6 and 0.5 nM, respectively.

IC50 value: 2.0/1.6/0.5 nM ( IGF–1R/InsR/ALK)Target: IGF–1R/InsR/ALK

GSK1838705A prevents the in vitro proliferation of cell lines derived from solid and hematologic malignancies, including multiplemyeloma and Ewing’s sarcoma, and retards the growth of human tumor xenografts in vivo. Despite the inhibitory effect of

GSK1838705A on insulin receptor, minimal effects on glucose homeostasis were obtained at efficacious doses. A single oral dose ofGSK1838705A at 0.1 and 0.3 mg/kg led to 35% and 65% prevention of IGF–IR phosphorylation, respectively, whereas doses ≥1 mg/kgled to complete inhibition of ligand–induced IGF–IR phosphorylation. Meanwhile, at a dose of 30 mg/kg, prevention was lasted for  24 hours after compound injection. GSK1838705A also suppresses the anaplastic lymphoma kinase (ALK), which mediates the aberrantgrowth of anaplastic large–cell lymphomas, some neuroblastomas, and a subset of non–small cell lung cancers. Due to its inhibition ofALK, GSK1838705A gives rise to complete regression of ALK–dependent tumors in vivo at well–tolerated doses.

PROTOCOL (Extracted from published papers and Only for reference)

Kinase assay [1]

Baculovirus–expressed glutathione S–transferase–tagged proteins encoding the intracellular domain of IGF–IR and IR were used fordeterminations of IC50s by a homogeneous time–resolved fluorescence assay. A filter binding assay was used for appKideterminations using activated IGF–IR and IR kinases. Expanded kinase–selectivity profiling of GSK1838705A was carried out byscreening the compound in the KinaseProfiler panel.Cell assay (Flow cytometry) [1]

Exponentially growing cells were seeded into 96–well tissue culture plates overnight at 37°C and treated with GSK1838705A for 24 and48 h. Plates were processed for flow cytometry using the Vindelov method. Cell cycle analyses were done using a FACSCalibur andFlowJo software.Animal administration [1]

Exponentially growing cells were implanted s.c. into the right flank of 8– to 12–wk–old female nu/nu CD–1 or SCID mice. When thetumors reached ?200 mm3 in size, the animals were weighed and block randomized according to tumor size into treatment groups ofeight mice each. Mice were dosed p.o. with the formulating vehicle or GSK1838705A. Mice were weighed and tumors measured bycalipers twice weekly. Tumor volumes were calculated using the following formula: tumor volume = (length × width2)/2. Thepercentage of tumor growth inhibition was calculated on each day of tumor measurement using the following formula: 100 × [1 –

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(average growth of the compound–treated tumors/average growth of vehicle–treated control tumors)].

References:

[1]. Sabbatini P, et al. GSK1838705A inhibits the insulin–like growth factor–1 receptor and anaplastic lymphoma kinase and shows antitumor activity inexperimental models of human cancers. Mol Cancer Ther. 2009 Oct;8(10):2811–20.

Caution: Product has not been fully validated for medical applications. For research use only.

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