Home Protein Tyrosine Kinase ALK inhibitor - IGF-1R inhibitor GSK1838705A For research use only.

GSK1838705A

GSK1838705A is a potent IGF-1R inhibitor with IC50 of 2.0 nM, modestly potent to IR and ALK with IC50 of 1.6 nM and 0.5 nM, respectively, and little activity to other protein kinases.

GSK1838705A Chemical Structure

GSK1838705A Chemical Structure

CAS: 1116235-97-2

Selleck's GSK1838705A has been cited by 18 Publications

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Purity & Quality Control

Batch: Purity: 99.3%
99.3

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Biological Activity

Description GSK1838705A is a potent IGF-1R inhibitor with IC50 of 2.0 nM, modestly potent to IR and ALK with IC50 of 1.6 nM and 0.5 nM, respectively, and little activity to other protein kinases.
Features A small-molecule kinase inhibitor of IGF-1R and the insulin receptor.
Targets
ALK [1]
(Cell-free assay)		 Insulin Receptor [1]
(Cell-free assay)		 IGF-1R [1]
(Cell-free assay)
0.5 nM 1.6 nM 2 nM
In vitro
In vitro GSK1838705A potently and ATP-competitively inhibits IGF-1R and IR with appKi values of 0.7 nM and 1.1 nM, respectively.In cells, GSK1838705A potently inhibits ligand-induced phosphorylation of IGF-1R and IR with IC50 of 85 nM and 79 nM, respectively. GSK1838705A shows the significant anti-proliferative effect in a panel of cell lines derived from solid and hematologic tumors such as L-82, SUP-M2, SK-ES and MCF-7 cells with EC50 of 24 nM, 28 nM, 141 nM and 203 nM, respectively. GSK1838705A shows an accumulation of MCF-7 and NCl-H929 cells predominantly in G1 (2N) phase of the cell cycle. GSK1838705A also inhibits ALK with Ki of 0.35 nM and supresses the proliferation of nucleophosmin (NPM)-ALK fusion cells with EC50 of 24-88 nM. GSK1838705A potently inhibits NPM-ALK phosphorylation in Karpas-299 and SR-786 cells, while has modest effect on STAT3 phosphorylation. [1]
Kinase Assay Kinase Assays
Baculovirus-expressed glutathione S-transferase-tagged proteins encoding the intracellular domain of IGF-1R (amino acids 957-1367) and IR (amino acids 979-1382) are used for determinations of IC50s by a homogeneous time-resolved fluorescence assay. A filter binding assay is used for appKi determinations using activated IGF-1R and IR kinases. Expanded kinase-selectivity profiling of GSK1838705A is carried out by screening the compound in the KinaseProfiler panel.
Cell Research Cell lines L-82, SUP-M2, SK-ES and MCF-7
Concentrations 0 to 10 μM
Incubation Time 72 hours
Method Cells are seeded in 96-well dishes, incubated overnight at 37 °C, and treated with DMSO or GSK1838705A for 72 hours. For the NIH-3T3/LISN proliferation assays, cells are seeded on collagen-coated 96-well tissue culture plates and allowed to adhere for 24 hours. The medium is replaced with serum-free medium and the cells are treated with GSK1838705A for 2 hour. Cells are incubated for 72 hours after addition of IGF-I (30 ng/mL). Cell proliferation is quantified using the CellTiter-Glo Luminescent Cell Viability Assay. IC50s are determined from cytotoxicity curves using a four-parameter curve fit software package (XLfit4
In Vivo
In vivo In NIH-3T3/LISN tumor-bearing mice, oral treatment of GSK1838705A (60 mg/kg) cause tumor growth inhibition by 77%, without significant weight loss. In COLO 205 tumor-bearing mice, inhibition of tumor growth by GSK1838705A (30 mg/kg) is 80%. Besides, the antitumor efficacy of GSK1838705A is also observed in mice bearing HT29 xenograft or BxPC3 xenograft. In mice, GSK1838705A (60 mg/kg) leads to a transient 2-fold increase in blood glucose levels by inhibiting IR signaling. GSK1838705A (60 mg/kg) inhibits the growth of established Karpas-299 xenografts with 93% tumor growth inhibition, with no effect on weights of the rats. [1]
Animal Research Animal Models L-82, SUP-M2, SK-ES and MCF-7 cells are injected s.c. into the right flank of CD1 or SCID mice.
Dosages ≤60 mg/kg
Administration Administered via p.o.

Chemical lnformation & Solubility

Molecular Weight 532.57 Formula

C27H29FN8O3
CAS No. 1116235-97-2 SDF Download GSK1838705A SDF
Smiles CNC(=O)C1=C(C=CC=C1F)NC2=NC(=NC3=C2C=CN3)NC4=C(C=C5CCN(C5=C4)C(=O)CN(C)C)OC
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 107 mg/mL ( (200.91 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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