Home Protein Tyrosine Kinase ALK inhibitor - IGF-1R inhibitor GSK1838705A

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GSK1838705A ALK inhibitor

Cat.No.S2703

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 ALK inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 532.57

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Chemical Information, Storage & Stability

Molecular Weight 532.57 Formula

C27H29FN8O3

 Storage (From the date of receipt)
CAS No. 1116235-97-2 Download SDF Storage of Stock Solutions

Synonyms N/A 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

Solubility

In vitro
Batch:

DMSO : 107 mg/mL (200.91 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
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Mechanism of Action

Features
A small-molecule kinase inhibitor of IGF-1R and the insulin receptor.
Targets/IC50/Ki
ALK [1]
(Cell-free assay)
0.5 nM
Insulin Receptor [1]
(Cell-free assay)
1.6 nM
IGF-1R [1]
(Cell-free assay)
2 nM
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, this compound potently inhibits ligand-induced phosphorylation of IGF-1R and IR with IC50 of 85 nM and 79 nM, respectively. It 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. This chemical shows an accumulation of MCF-7 and NCl-H929 cells predominantly in G1 (2N) phase of the cell cycle. It 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. This compound 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 this compound is carried out by screening it in the KinaseProfiler panel.
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 this compound (30 mg/kg) is 80%. Besides, the antitumor efficacy of this chemical is also observed in mice bearing HT29 xenograft or BxPC3 xenograft. In mice, this compound (60 mg/kg) leads to a transient 2-fold increase in blood glucose levels by inhibiting IR signaling. It (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]
References

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