![3-(2-(Trifluoromethyl)benzyloxy)-5-(5,6-dimethoxy-1H-benzo[d]imidazol-1-yl)thiophene-2-carboxamide structure, CAS 660868-91-7](/structures/60000/57822_1_660868_91_7.png)
| Chemical & Physical Properties | |
|---|---|
| CAS Number | 660868-91-7 |
| Catalog No. | 2A-9057822 |
| Chinese Name | 3-[2-(三氟甲基)苄氧基]-5-(5,6-二甲氧基-1H-苯并[d]咪唑-1-基)-2-噻吩甲酰胺 |
| Synonyms | thiophene deriv.,20; Kinome_3462; GW 843682X; GW843682X |
| Molecular Formula | C22H18F3N3O4S |
| Molecular Weight | 477.46 |
| Purity | ≥98 (HPLC) |
| Density | 1.4±0.1 g/cm3 |
| Boiling Point | 629.6±65.0 °C at 760 mmHg |
| Appearance | solid |
| Storage Condition | 2-8℃ |
| Application | GW843682X is a selective, ATP-competitive inhibitor of PLK1 and PLK3 with IC50 values of 2.2 nM and 9.1 nM respectively. It is more than 100 times more selective than other 30 kinases. |
| PubChem ID | 329799898 |
| MDL Number | MFCD09971143 |
| SMILES | COc1cc2ncn(-c3cc(OCc4ccccc4C(F)(F)F)c(s3)C(N)=O)c2cc1OC |
| InChI | 1S/C22H18F3N3O4S/c1-30-16-7-14-15(8-17(16)31-2)28(11-27-14)19-9-18(20(33-19)21(26)29)32-10-12-5-3-4-6-13(12)22(23,24)25/h3-9,11H,10H2,1-2H3,(H2,26,29) |
| InChI Key | JSKUWFIZUALZLX-UHFFFAOYSA-N |
| NACRES Code | NA.77 |
| UNSPSC | 12352200 |
| MSDS | msds/57822_1_660868_91_7.pdf |
| Bioactivity | GW843682X is a selective, ATP-competitive inhibitor of PLK1 and PLK3, with IC50s of 2.2 nM and 9.1 nM, respectively, and is also >100-fold selective against ∼30 other kinases. Related Catalog Signaling Pathways >> Cell Cycle/DNA Damage >> Polo-like Kinase (PLK) Research Areas >> Cancer Target PLK1:2.2 nM (IC50) PLK3:9.1 nM (IC50) PDGFR1β:160 nM (IC50) VEGFR2:360 nM (IC50) Aurora A:4800 nM (IC50) CDK2/cyclin A:7600 nM (IC50) In Vitro GW843682X (compound 1) is effective on inhibition of growth of tumor cells, with IC50s of 0.41, 0.57, 0.11, 0.38, and 0.70 μM for A549, BT474, HeLa, H460 and HCT116 cell lines. GW843682X dose-dependently inhibits PLK1 phosphorylation of Ser15-p53, with an IC50 of 0.14 μM. GW843682X (3 μM) causes a strong G2-M arres in HDF cells and H460 cells after treatment for 24, 48, and 72 h. GW843682X (5 μM) leads to apoptosis in H460 cells instead of HDF cells[1]. GW843682X inhibits proliferation of U937 cells with an EC50 of 120 nM. GW843682X (500 nM) in combination with 5 µM VP-16 suppresses 50% of entry into mitosis in U937 cells[2]. GW843682X (0.06-1 μM) has inhibitory activities against proliferation of acute leukemia cells, and potentiates the anti-proliferative activity of vincristine. Moreover, GW843682X (0.1-1 μM) induces apoptosis of leukemia cells in a dose- and time-dependent manner. GW843682X (0.5-1 μM) dephosphorylates Bcl-xl in leukemia cells[3]. Kinase Assay PLK1 and PLK3 proteins are prepared from baculovirus-infected Trichoplusia ni cells. Enzyme activity for PLK1 and PLK3 is determined as follows. All measurements are obtained under conditions where signal production increased linearly with time and enzyme. Test compounds are added to white 384-well assay plates (0.1 μL for 10 μL and some 20 μL assays, 1 μL for some 20 μL assays) at variable known concentrations in 100% DMSO. DMSO (1-5% final) and EDTA (65 mM) are used as controls. Reaction Mix containes the following components at 22°C: 25 mM HEPES (pH 7.2); 15 mM MgCl2; 1 μM ATP; 0.05 μCi/well [γ-33P]ATP (10 Ci/mmol); 1 μM substrate peptide (Biotin-Ahx-SFNDTLDFD); 0.15 mg/mL bovine serum albumin; 1 mM DTT; and 2 nM PLK1 kinase domain or 5 nM full-length PLK3. Reaction Mix (10 or 20 μL) is quickly added to each well immediately following addition of enzyme via automated liquid handlers and incubated for 1 to 1.5 h at 22°C. The 20 μL enzymatic reactions are stopped with 50 μL of stop mix [50 mM EDTA, 4.0 mg/mL streptavidin SPA beads in Dulbecco's PBS (without Mg2+ and Ca2+), 50 μM ATP] per well. The 10 μL reactions are stopped with 10 μL of stop mix [50 mM EDTA, 3.0 mg/mL streptavidin-coupled SPA Imaging Beadsin Dulbecco's PBS (without Mg2+ and Ca2+), 50 μM ATP] per well. Plates are sealed, spun at 500 × g for 1 min or settled overnight, and counted in Packard TopCount for 30 s/well or imaged with a Viewlux imager. Signal above background (EDTA controls) is converted to percent inhibition relative to that obtained in control (DMSO-only) wells[1]. Cell Assay Assays are carried out and data analyzed. In these assays, H460 cells are plated at a density of 2,000 per well, HDF cells are plated at 5,000 per well, and the drug-resistant cell line MES-SA/DX5 and its sensitive parent line MES-SA are plated at 7,000 and 6,000 per well, respectively, in a 96-well plate. These densities allowed vehicle controls to grow logarithmically during the course of the 3-day assay. All cells are exposed to 3-fold dilutions of the compound (30-0.00152 μM) in low-glucose DMEM containing 5% FBS, 50 μg/mL gentamicin, and 0.3% (v/v) DMSO (HDF cells); RPMI 1640 containing 5% FBS, 50 μg/mL gentamicin, and 0.3% (v/v) DMSO (H460); or McCoy's 5A containing 5% FBS, 50 μg/mL gentamicin, and 0.3% (v/v) DMSO (MES-SA and MES-SA/DX5)[1]. References [1]. Lansing TJ, et al. In vitro biological activity of a novel small-molecule inhibitor of polo-like kinase 1. Mol Cancer Ther. 2007 Feb;6(2):450-9. Epub 2007 Jan 31. [2]. Didier C, et al. Evaluation of Polo-like Kinase 1 inhibition on the G2/M checkpoint in Acute Myelocytic Leukaemia. Eur J Pharmacol. 2008 Sep 4;591(1-3):102-5. [3]. Ikezoe T, et al. A novel treatment strategy targeting polo-like kinase 1 in hematological malignancies. Leukemia. 2009 Sep;23(9):1564-76. Chemical & Physical Properties Density 1.4±0.1 g/cm3 Boiling Point 629.6±65.0 °C at 760 mmHg Molecular Formula C22H18F3N3O4S Molecular Weight 477.46 Flash Point 334.6±34.3 °C PSA 116.84000 LogP 4.25 Vapour Pressure 0.0±1.8 mmHg at 25°C Index of Refraction 1.613 InChIKey JSKUWFIZUALZLX-UHFFFAOYSA-N SMILES COc1cc2ncn(-c3cc(OCc4ccccc4C(F)(F)F)c(C(N)=O)s3)c2cc1OC Storage condition 2-8℃ |
| Use of | GW843682X is a selective, ATP-competitive inhibitor of PLK1 and PLK3, with IC50s of 2.2 nM and 9.1 nM, respectively, and is also >100-fold selective against ∼30 other kinases. Properties Name 5-(5,6-dimethoxybenzimidazol-1-yl)-3-[[2-(trifluoromethyl)phenyl]methoxy]thiophene-2-carboxamide Synonym More Synonyms GW843682X Biological Activity Description GW843682X is a selective, ATP-competitive inhibitor of PLK1 and PLK3, with IC50s of 2.2 nM and 9.1 nM, respectively, and is also >100-fold selective against ∼30 other kinases. Related Catalog Signaling Pathways >> Cell Cycle/DNA Damage >> Polo-like Kinase (PLK) Research Areas >> Cancer PLK1:2.2 nM (IC50) PLK3:9.1 nM (IC50) PDGFR1β:160 nM (IC50) VEGFR2:360 nM (IC50) Aurora A:4800 nM (IC50) References [1]. Lansing TJ, et al. In vitro biological activity of a novel small-molecule inhibitor of polo-like kinase 1. Mol Cancer Ther. 2007 Feb;6(2):450-9. Epub 2007 Jan 31. [3]. Ikezoe T, et al. A novel treatment strategy targeting polo-like kinase 1 in hematological malignancies. Leukemia. 2009 Sep;23(9):1564-76. Chemical & Physical Properties Molecular Formula C22H18F3N3O4S PSA 116.84000 Index of Refraction 1.613 InChIKey JSKUWFIZUALZLX-UHFFFAOYSA-N Storage condition 2-8℃ |
| Transport Info | Product name: GW843682X |
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