HI TOPK 032CAS# 487020-03-1 |
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Quality Control & MSDS
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| Cas No. | 487020-03-1 | SDF | Download SDF |
| PubChem ID | 1936439 | Appearance | Powder |
| Formula | C20H11N5OS | M.Wt | 369.4 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 7.5 mg/mL (20.30 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | N-(12-cyanoindolizino[2,3-b]quinoxalin-2-yl)thiophene-2-carboxamide | ||
| SMILES | C1=CC=C2C(=C1)N=C3C(=C4C=C(C=CN4C3=N2)NC(=O)C5=CC=CS5)C#N | ||
| Standard InChIKey | BCSBXWKRZUPFHW-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C20H11N5OS/c21-11-13-16-10-12(22-20(26)17-6-3-9-27-17)7-8-25(16)19-18(13)23-14-4-1-2-5-15(14)24-19/h1-10H,(H,22,26) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | T-LAK-cell-originated protein kinase (TOPK) inhibitor; exhibits selectivity for TOPK over other MAPKK family members including ERK1, JNK1 and p38. Blocks proliferation of HCT116 colon cancer cells; suppresses tumor growth in a colon cancer xenograft model. Also inhibits Chk1 (IC50 = 9.6 μM). |
HI TOPK 032 Dilution Calculator
HI TOPK 032 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.7071 mL | 13.5355 mL | 27.0709 mL | 54.1419 mL | 67.6773 mL |
| 5 mM | 0.5414 mL | 2.7071 mL | 5.4142 mL | 10.8284 mL | 13.5355 mL |
| 10 mM | 0.2707 mL | 1.3535 mL | 2.7071 mL | 5.4142 mL | 6.7677 mL |
| 50 mM | 0.0541 mL | 0.2707 mL | 0.5414 mL | 1.0828 mL | 1.3535 mL |
| 100 mM | 0.0271 mL | 0.1354 mL | 0.2707 mL | 0.5414 mL | 0.6768 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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HI-TOPK-032 is a potent and specific TOPK inhibitor.
In Vitro:HI-TOPK-032 strongly suppresses TOPK kinase activity but has little effect on extracellular signal-regulated kinase 1 (ERK1), c-jun-NH2-kinase 1, or p38 kinase activities. HI-TOPK-032 occupies the ATP-binding site of TOPK and fits the binding site very well. The compound forms hydrogen bonds with GLY83 and ASP151 and has a hydrophobic interaction with LYS30. However, HI-TOPK-032 at the highest concentration (5 μM) also inhibits MEK1 activity by 40%. HI-TOPK-032 also inhibits anchorage-dependent and -independent colon cancer cell growth by reducing ERK-RSK phosphorylation as well as increasing colon cancer cell apoptosis through regulation of the abundance of p53, cleaved caspase-7, and cleaved PARP[1].
In Vivo:Treatment of mice with 1 or 10 mg/kg of HI-TOPK-032 significantly inhibits HCT-116 tumor growth by more than 60% relative to the vehicle-treated group. Mice are well tolerated with HI-TOPK-032 treatment. The expression of p53 is strongly induced, and phosphorylation of ERK and RSK, a direct downstream protein of ERK, is markedly inhibited in the HI-TOPK-032-treated group[1].
References:
[1]. Kim DJ, et al. Novel TOPK inhibitor HI-TOPK-032 effectively suppresses colon cancer growth. Cancer Res. 2012 Jun 15;72(12):3060-8.
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Novel TOPK inhibitor HI-TOPK-032 effectively suppresses colon cancer growth.[Pubmed:22523035]
Cancer Res. 2012 Jun 15;72(12):3060-8.
The serine-threonine mitogen-activated protein kinase kinase family member T-LAK cell-originated protein kinase (TOPK/PBK) is heavily involved in tumor development, cancer growth, apoptosis, and inflammation. Despite the identification of TOPK as a promising novel therapeutic target, no inhibitor of TOPK has yet been reported. In this study, we screened 36 drug candidates using an in vitro kinase assay and identified the novel TOPK inhibitor HI-TOPK-032. In vitro, HI-TOPK-032 strongly suppressed TOPK kinase activity but had little effect on extracellular signal-regulated kinase 1 (ERK1), c-jun-NH2-kinase 1, or p38 kinase activities. HI-TOPK-032 also inhibited anchorage-dependent and -independent colon cancer cell growth by reducing ERK-RSK phosphorylation as well as increasing colon cancer cell apoptosis through regulation of the abundance of p53, cleaved caspase-7, and cleaved PARP. In vivo, administration of HI-TOPK-032 suppressed tumor growth in a colon cancer xenograft model. Our findings therefore show that HI-TOPK-032 is a specific inhibitor of TOPK both in vitro and in vivo that may be further developed as a potential therapeutic against colorectal cancer.
Discovery of novel checkpoint kinase 1 inhibitors by virtual screening based on multiple crystal structures.[Pubmed:21955044]
J Chem Inf Model. 2011 Nov 28;51(11):2904-14.
Incorporating receptor flexibility is considered crucial for improvement of docking-based virtual screening. With an abundance of crystallographic structures freely available, docking with multiple crystal structures is believed to be a practical approach to cope with protein flexibility. Here we describe a successful application of the docking of multiple structures to discover novel and potent Chk1 inhibitors. Forty-six Chk1 structures were first compared in single structure docking by predicting the binding mode and recovering known ligands. Combinations of different protein structures were then compared by recovery of known ligands and an optimal ensemble of Chk1 structures were selected. The chosen structures were used in the virtual screening of over 60 000 diverse compounds for Chk1 inhibitors. Six novel compounds ranked at the top of the hits list were tested experimentally, and two of these compounds inhibited Chk1 activity-the best with an IC(50) value of 9.6 muM. Further study indicated that achieving a better enrichment and identifying more diverse compounds was more likely using multiple structures than using only a single structure even when protein structures were randomly selected. Taking into account conformational energy difference did not help to improve enrichment in the top ranked list.
