product name GSK1838705A
Description: GSK1838705A is a potent small-molecule IGF-1R inhibitor with IC50 of 2.0 nM, it is modestly potent to IR and ALK with IC50 of 1.6 nM and 0.5 nM, respectively, and has little activity to other protein kinases. GSK1838705A blocks the in vitro proliferation of cell lines derived from solid and hematologic malignancies, including multiple myeloma and Ewings sarcoma, and retards the growth of human tumor xenografts in vivo.
References: Mol Cancer Ther. 2009 Oct;8(10):2811-20.
532.57
Formula
C27H29FN8O3
CAS No.
1116235-97-2
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 107 mg/mL (200.9 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
15% Captisol+citrate vehicle: 30 mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19399209
| In Vitro |
In vitro activity: 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. Kinase Assay: 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 Assay:Cells ( L-82, SUP-M2, SK-ES and MCF-7) 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. |
|---|---|
| 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. |
| Animal model | L-82, SUP-M2, SK-ES and MCF-7 cells are injected s.c. into the right flank of CD1 or SCID mice. |
| Formulation & Dosage | Dissolved in 20% sulfobutyl ether β-cyclodextrin (ISP; pH 3.5); 60 mg/kg; Oral gavage |
| References | Mol Cancer Ther. 2009 Oct;8(10):2811-20. |
Related Posts
product name GSK1838705A
Description: GSK1838705A is a potent small-molecule IGF-1R inhibitor with IC50 of 2.0 nM, it is modestly potent to IR and ALK with IC50 of 1.6 nM and 0.5 nM, respectively, and has little activity to other protein kinases. GSK1838705A blocks the in vitro proliferation of cell lines derived from solid and hematologic malignancies, including multiple myeloma and Ewings sarcoma, and retards the growth of human tumor xenografts in vivo.
References: Mol Cancer Ther. 2009 Oct;8(10):2811-20.
532.57
Formula
C27H29FN8O3
CAS No.
1116235-97-2
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 107 mg/mL (200.9 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
15% Captisol+citrate vehicle: 30 mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19399209
| In Vitro |
In vitro activity: 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. Kinase Assay: 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 Assay:Cells ( L-82, SUP-M2, SK-ES and MCF-7) 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. |
|---|---|
| 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. |
| Animal model | L-82, SUP-M2, SK-ES and MCF-7 cells are injected s.c. into the right flank of CD1 or SCID mice. |
| Formulation & Dosage | Dissolved in 20% sulfobutyl ether β-cyclodextrin (ISP; pH 3.5); 60 mg/kg; Oral gavage |
| References | Mol Cancer Ther. 2009 Oct;8(10):2811-20. |