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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 | C18H13F3N4O2 |
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分子量 | 374.32 | CAS No. | 778270-11-4 | |
Solubility (25°C)* | 体外 | DMSO | 75 mg/mL (200.36 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 | GNF-2 is a highly selective non-ATP competitive inhibitor of Bcr-Abl, shows no activity to Flt3-ITD, Tel-PDGFR, TPR-MET and Tel-JAK1 transformed tumor cells. |
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in vitro | GNF-2 causes a dose-dependent growth inhibition of the Bcr-abl–positive cell lines with IC50 values of 273 nM (K562) and 268 nM (SUP-B15). GNF-2 inhibits the growth of Ba/F3.p210E255V and Ba/F3.p185Y253H cells with IC50 values of 268 nM and 194 nM respectively. GNF-2 (1 μM) induces apoptosis of Ba/F3.p210 cells as well as Ba/F3.p210E255V cells. GNF-2 inhibits the cellular tyrosine phosphorylation of Bcr-abl in a dose-dependent manner with IC50 of 267 nM. GNF-2 (1 μM) induces a significant decrease in the levels of phospho-Stat5 in Ba/F3.p210 cells. GNF-2 binds to the myristic binding pocket of Bcr-abl. [1] GNF-2 inhibits the kinase activity of non-myristoylated c-Abl more potently than that of myristoylated c-Abl by binding to the myristate-binding pocket in the C-lobe of the kinase domain. GNF-2 (10 μM) requires BCR and/or the c-Abl SH3 and/or SH2 domains to inhibit BCR-Abl-dependent cell proliferation. GNF-2, but not a methylated GNF-2 analog, binds c-Abl in cellular extracts derived from 3T3 fibroblasts. GNF-2 (10 μM), in a dose-dependent manner, clearly inhibits tyrosine phosphorylation of CrkII. GNF-2 inhibits the phosphorylation of CrkII in c-AblG2A-expressing cells with IC50 of 0.051 μM. [2] GNF-2 binds in an extended conformation in the myristate pocket with the CF3-group buried at the same depth as the final two carbons of the myristate ligand. GNF-2 (10 µM) combined with imatinib (1 µM) reduces the number of resistant clones to 1 µM imatinib by at least 90%. [3] GNF-2 inhibits the auto-phosphorylation and proliferation of BafF3 cells expressing p210Bcr–Abl and p210Bcr–Abl mutants. GNF-2 (8 nM) in combination with GNF-5 (20 nM) results in additive effects with respect to inhibition of the Abl64–515 kinase activity. [4] |
キナーゼアッセイ | Binding assay | |
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Recombinant proteins (100 nM for each construct) or immunoprecipitated proteins are diluted in kinase buffer (20 mM HEPES (pH 7.4), 50 mM KCl, 0.1% CHAPS, 30 mM MgCl2, 2 mM MnCl2, 1 mM DTT, and 1% glycerol). Aliquots of the diluted proteins are preincubated with either DMSO or compounds for 30 min at room temperature and then added to K-LISA PTK EAY reaction plates. The kinase reaction is initiated by adding 0.1 mM ATP and is allowed to proceed for 30 min at room temperature. The phosphorylation of GST-Abltide is monitored by SDS-PAGE and phosphorimaging analysis or autoradiography. | ||
細胞アッセイ | 細胞株 | Ba/F3.p210, Ba/F3.p210E255V and Ba/F3.p185Y253H cells |
濃度 | ~10 μM | |
反応時間 | 48 hours | |
実験の流れ | Cells (0.3-0.6 × 106 per mL) are plated in duplicate or triplicate in 96-well plates containing increasing GNF-2 concentrations (5 nM–10 μM). After incubation at 37 ℃ in 5% CO2 for 48 hours, the effect of GNF-2 on cell viability is determined by the MTT colorimetric dye reduction method. Inhibition of cell proliferation is calculated as a percentage of growth of DMSO-treated cells, and IC50 values are determined with Microsoft Excel XLfit3. |
Data from [Data independently produced by , , Oncotarget, 2017, 8(24):38717-38730]
A multiplexed siRNA screen identifies key kinase signaling networks of brain glia [ Life Sci Alliance, 2023, 6(5)e202201605] | PubMed: 36878638 |
Imatinib protects against human beta-cell death via inhibition of mitochondrial respiration and activation of AMPK [ Clin Sci (Lond), 2021, 135(19):2243-2263] | PubMed: 34569605 |
Quantitative, Wide-Spectrum Kinase Profiling in Live Cells for Assessing the Effect of Cellular ATP on Target Engagement [Vasta JD Cell Chem Biol, 2018, 25(2):206-214] | PubMed: 29174542 |
Abl and Arg mediate cysteine cathepsin secretion to facilitate melanoma invasion and metastasis [ Sci Signal, 2018, 11(518)eaao0422] | PubMed: 29463776 |
Abl and Arg mediate cysteine cathepsin secretion to facilitate melanoma invasion and metastasis [ Sci Signal, 2018, 11(518)eaao0422] | PubMed: 29463776 |
Coronavirus S protein-induced fusion is blocked prior to hemifusion by Abl kinase inhibitors. [ J Gen Virol, 2018, 99(5):619-630] | PubMed: 29557770 |
Comparative Characterization of Osteoclasts Derived From Murine Bone Marrow Macrophages and RAW 264.7 Cells Using Quantitative Proteomics. [ JBMR Plus, 2018, 2(6):328-340] | PubMed: 30460336 |
Abl kinase regulation by BRAF/ERK and cooperation with Akt in melanoma. [ Oncogene, 2017, 36(32):4585-4596] | PubMed: 28368422 |
Contributions of MET activation to BCR-ABL1 tyrosine kinase inhibitor resistance in chronic myeloid leukemia cells. [Tsubaki M, et al. Oncotarget, 2017, 8(24):38717-38730] | PubMed: 28418880 |
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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