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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C27H29FN8O3 |
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分子量 | 532.57 | CAS No. | 1116235-97-2 | |
Solubility (25°C)* | 体外 | DMSO | 107 mg/mL (200.91 mM) | |
Water | Insoluble | |||
Ethanol | Insoluble | |||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | 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. |
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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] |
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] |
特徴 | A small-molecule kinase inhibitor of IGF-1R and the insulin receptor. |
キナーゼアッセイ | Kinase Assays | |
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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. | ||
細胞アッセイ | 細胞株 | L-82, SUP-M2, SK-ES and MCF-7 |
濃度 | 0 to 10 μM | |
反応時間 | 72 hours | |
実験の流れ | 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 | |
動物実験 | 動物モデル | L-82, SUP-M2, SK-ES and MCF-7 cells are injected s.c. into the right flank of CD1 or SCID mice. |
投薬量 | ≤60 mg/kg | |
投与方法 | Administered via p.o. |
, , Mol Med Rep, 2015, 12(4):5641-6.
Data from [Data independently produced by , , Cell Oncol (Dordr), 2018, 41(3):283-296]
IGF-binding proteins secreted by cancer-associated fibroblasts induce context-dependent drug sensitization of lung cancer cells [ Sci Signal, 2022, 15(747):eabj5879] | PubMed: 35973030 |
Targeting Aurora B kinase prevents and overcomes resistance to EGFR inhibitors in lung cancer by enhancing BIM- and PUMA-mediated apoptosis [ Cancer Cell, 2021, S1535-6108(21)00383-4] | PubMed: 34388376 |
Efficient suppression of NRAS-driven melanoma by co-inhibition of ERK1/2 and ERK5 MAPK pathways. [ J Invest Dermatol, 2020, 3 pii: S0022-202X(20)31407-X] | PubMed: 32376279 |
Gene Essentiality Profiling Reveals Gene Networks and Synthetic Lethal Interactions with Oncogenic Ras. [ Cell, 2019, 36(2):179-193] | PubMed: 28162770 |
A Pharmacogenomic Landscape in Human Liver Cancers. [ Cancer Cell, 2019, 36(2):179-193] | PubMed: 31378681 |
Divergent Polypharmacology-Driven Cellular Activity of Structurally Similar Multi-Kinase Inhibitors through Cumulative Effects on Individual Targets [ Cell Chem Biol, 2019, 10.1016/j.chembiol.2019.06.003] | PubMed: 31257184 |
Extracellular Glutamate-Induced mTORC1 Activation via the IR/IRS/PI3K/Akt Pathway Enhances the Expansion of Porcine Intestinal Stem Cells [ J Agric Food Chem, 2019, 67(34):9510-9521] | PubMed: 31382738 |
Ramucirumab and GSK1838705A Enhance the Inhibitory Effects of Low Concentration Sorafenib and Regorafenib Combination on HCC Cell Growth and Motility. [ Cancers (Basel), 2019, 11(6)] | PubMed: 31181647 |
Strong enhancement by IGF1-R antagonists of hepatocellular carcinoma cell migration inhibition by Sorafenib and/or vitamin K1 [D'Alessandro R, et al. Cell Oncol (Dordr), 2018, 41(3):283-296] | PubMed: 29470830 |
IGF-1R tyrosine kinase inhibitors and Vitamin K1 enhance the antitumor effects of Regorafenib in HCC cell lines. [ Oncotarget, 2017, 8(61):103465-103476] | PubMed: 29262576 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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