TAI-1Hec1 inhibitor, potent, first-in-class CAS# 1334921-03-7 |
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Quality Control & MSDS
3D structure
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| Cas No. | 1334921-03-7 | SDF | Download SDF |
| PubChem ID | 53389629 | Appearance | Powder |
| Formula | C24H21N3O3S | M.Wt | 431.51 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | Soluble in DMSO > 10 mM | ||
| Chemical Name | N-[4-[4-(4-methoxyphenoxy)-2,6-dimethylphenyl]-1,3-thiazol-2-yl]pyridine-4-carboxamide | ||
| SMILES | CC1=CC(=CC(=C1C2=CSC(=N2)NC(=O)C3=CC=NC=C3)C)OC4=CC=C(C=C4)OC | ||
| Standard InChIKey | NBNNDUZYMXBCOX-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C24H21N3O3S/c1-15-12-20(30-19-6-4-18(29-3)5-7-19)13-16(2)22(15)21-14-31-24(26-21)27-23(28)17-8-10-25-11-9-17/h4-14H,1-3H3,(H,26,27,28) | ||
| 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. | ||
TAI-1 Dilution Calculator
TAI-1 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.3174 mL | 11.5872 mL | 23.1744 mL | 46.3489 mL | 57.9361 mL |
| 5 mM | 0.4635 mL | 2.3174 mL | 4.6349 mL | 9.2698 mL | 11.5872 mL |
| 10 mM | 0.2317 mL | 1.1587 mL | 2.3174 mL | 4.6349 mL | 5.7936 mL |
| 50 mM | 0.0463 mL | 0.2317 mL | 0.4635 mL | 0.927 mL | 1.1587 mL |
| 100 mM | 0.0232 mL | 0.1159 mL | 0.2317 mL | 0.4635 mL | 0.5794 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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TAI-1 is a highly potent, first-in-class inhibitor of Hec1 with IC50 of
TAI-1 has a GI50 of 13.48 nM (K562 cells), which is close to 1000 times improvement in potency compared to INH1 (GI50 =11.7 μM). TAI-1 showed strong inhibition across a broad spectrum of tumor cells. TAI-1 interrupted Hec1-Nek2 protein interaction, led to Nek2 degradation, induced significant chromosomal misalignment in metaphase, and induced apoptotic cell death. TAI-1 was orally active in in vivo animal models of triple negative colon cancer, breast cancer and liver cancer. Preliminary toxicity shows no effect on the organ weights, body weights and blood indices at efficacious doses. TAI-1 shows high specificity to cancer cells and to target and had no effect on the cardiac channel hERG. TAI-1 is synergistic with topotecan, doxorubicin and paclitaxel in breast, leukemia and liver cancer cells. Sensitivity to TAI-1 was associated with the status of P53 and RB gene. Knockdown of P53 and RB in cancer cells increased sensitivity to TAI-1.
References:
[1]. Huang LY, Lee YS, Huang JJ et al. Characterization of the biological activity of a potent small molecule Hec1 inhibitor TAI-1. J Exp Clin Cancer Res. 2014 Jan 9;33:6. doi: 10.1186/1756-9966-33-6.
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Characterization of the biological activity of a potent small molecule Hec1 inhibitor TAI-1.[Pubmed:24401611]
J Exp Clin Cancer Res. 2014 Jan 9;33:6.
BACKGROUND: Hec1 (NDC80) is an integral part of the kinetochore and is overexpressed in a variety of human cancers, making it an attractive molecular target for the design of novel anticancer therapeutics. A highly potent first-in-class compound targeting Hec1, TAI-1, was identified and is characterized in this study to determine its potential as an anticancer agent for clinical utility. METHODS: The in vitro potency, cancer cell specificity, synergy activity, and markers for response of TAI-1 were evaluated with cell lines. Mechanism of action was confirmed with western blotting and immunofluorescent staining. The in vivo potency of TAI-1 was evaluated in three xenograft models in mice. Preliminary toxicity was evaluated in mice. Specificity to the target was tested with a kinase panel. Cardiac safety was evaluated with hERG assay. Clinical correlation was performed with human gene database. RESULTS: TAI-1 showed strong potency across a broad spectrum of tumor cells. TAI-1 disrupted Hec1-Nek2 protein interaction, led to Nek2 degradation, induced significant chromosomal misalignment in metaphase, and induced apoptotic cell death. TAI-1 was effective orally in in vivo animal models of triple negative breast cancer, colon cancer and liver cancer. Preliminary toxicity shows no effect on the body weights, organ weights, and blood indices at efficacious doses. TAI-1 shows high specificity to cancer cells and to target and had no effect on the cardiac channel hERG. TAI-1 is synergistic with doxorubicin, topotecan and paclitaxel in leukemia, breast and liver cancer cells. Sensitivity to TAI-1 was associated with the status of RB and P53 gene. Knockdown of RB and P53 in cancer cells increased sensitivity to TAI-1. Hec1-overexpressing molecular subtypes of human lung cancer were identified. CONCLUSIONS: The excellent potency, safety and synergistic profiles of this potent first-in-class Hec1-targeted small molecule TAI-1 show its potential for clinically utility in anti-cancer treatment regimens.
