THZ2CDK7 inhibitor CAS# 1604810-84-5 |
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Quality Control & MSDS
3D structure
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| Cas No. | 1604810-84-5 | SDF | Download SDF |
| PubChem ID | 78357763 | Appearance | Powder |
| Formula | C31H28ClN7O2 | M.Wt | 566.05 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 39 mg/mL (68.90 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | N-[3-[[5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl]amino]phenyl]-3-[[(E)-4-(dimethylamino)but-2-enoyl]amino]benzamide | ||
| SMILES | CN(C)CC=CC(=O)NC1=CC=CC(=C1)C(=O)NC2=CC=CC(=C2)NC3=NC=C(C(=N3)C4=CNC5=CC=CC=C54)Cl | ||
| Standard InChIKey | FONRCZUZCHXWBD-VGOFMYFVSA-N | ||
| Standard InChI | InChI=1S/C31H28ClN7O2/c1-39(2)15-7-14-28(40)35-21-9-5-8-20(16-21)30(41)36-22-10-6-11-23(17-22)37-31-34-19-26(32)29(38-31)25-18-33-27-13-4-3-12-24(25)27/h3-14,16-19,33H,15H2,1-2H3,(H,35,40)(H,36,41)(H,34,37,38)/b14-7+ | ||
| 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 | THZ2 is a potent and selective CDK7 inhibitor with IC50 of 13.9 nM.In Vitro:THZ2 selectively targets CDK7 and potently inhibits the growth of triple-negative but not ER/PR+ breast cancer cells. THZ2 at low nanomolar doses also efficiently suppresses the clonogenic growth of TNBC cells with IC50 of appr 10 nM. THZ2 induces apoptotic cell death in triple-negative but not ER/PR+ breast cancer cells or normal human cells[1].In Vivo:THZ2 (10 mg/Kg) markedly reduces the growth rate of tumors in mice and demonstrates an anti-tumor activity. Compared to vehicle-treated tumors, tumor tissues isolated from mice treated with THZ2 has reduced proliferation and increased apoptosis, as indicated by immunostaining against Ki67 and cleaved Caspase 3 respectively. THZ2 in NOD-SCID mice leads to reduced body weight, suggesting that THZ2 mayt be less well-tolerated in this particular mouse strain[1]. References: | |||||
Cell Assay
[1]
For 96-well plate assay, cells are plated at the density of 2000 cells per well, and on the next day treated with THZ1 or THZ2 of various concentrations. After 48-hour incubation, cells are fixed and stained with crystal violet. The staining is then extracted by adding each well with 10% acetic acid, with absorbance measured at 590 nm with 750 nm as a reference.
Animal Administration
[1]
Mice: Nude mice (CrTac:NCr-Foxn1nu) are γ-irradiated with a single dose of 400 rads six hours before transplantation of cells. Breast cancer cells are harvested and resupended in 40% Matrigel-Basement Membrane Matrix, LDEV-free, and then injected (100 μL per site) into the fourth pair of mammary fat pads of mice. Tumors are measured in two dimensions by using manual calipers. Tumor volume is calculated using the formula: V=0.5× length × width × width. Animal with tumor established (mean tumor volume of appr 200 mm3) are randomLy divided into two groups, which are then treated with vehicle (10% DMSO in D5W, 5% dextrose in water) or THZ2 (3 mg/mL, prepared in vehicle solutions) at the dose of 10 mg/kg intraperitoneally twice daily. Tumor volume is measure every 2-3 days. Upon harvesting tumors, tumors are cut into half, with one half fixed in formalin overnight and then in 70% ethanol for histopathology analysis, and the other half snap frozen in liquid nitrogen for immunoblotting.
References:
[1]. Wang Y, et al. CDK7-Dependent Transcriptional Addiction in Triple-Negative Breast Cancer. Cell. 2015 Sep 24;163(1):174-186.
THZ2 Dilution Calculator
THZ2 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 1.7666 mL | 8.8331 mL | 17.6663 mL | 35.3326 mL | 44.1657 mL |
| 5 mM | 0.3533 mL | 1.7666 mL | 3.5333 mL | 7.0665 mL | 8.8331 mL |
| 10 mM | 0.1767 mL | 0.8833 mL | 1.7666 mL | 3.5333 mL | 4.4166 mL |
| 50 mM | 0.0353 mL | 0.1767 mL | 0.3533 mL | 0.7067 mL | 0.8833 mL |
| 100 mM | 0.0177 mL | 0.0883 mL | 0.1767 mL | 0.3533 mL | 0.4417 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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THZ2 is a potent and selective CDK7 inhibitor (IC50=13.9 nM).
Cyclin-dependent kinase (CDK) is a group of serine/threonine kinases. It is activated by binding to cyclin and participates in the regulation of cell cycle.
THZ2 selectively targets CDK7 and potently blocks the proliferation of triple-negative breast cancer (TNBC) cells and induces apoptotic cell death without causing alteration in cell cycle. The low nanomolar dose of THZ2 also inhibits the clonogenic growth of TNBC cells with IC50 of 10 nM.
THZ2 is well tolerant in mice as 10 mg/kg intraperitoneal treatment of THZ2 twice daily does not cause weight loss or behavioral changes. THZ2 treatment also significantly reduces the tumor growth rate mice. In addition, both acute (50 hr) or chronic (25 days) exposure to THZ markedly decreases CTD phosphorylation of RNAPII at all three phosphorylation sites as indication of CDk7 being efficiently targeted.
Reference:
1. Wang Y, Zhang T, Kwiatkowski N et al. CDK7-dependent transcriptional addiction in triple-negative breast cancer. Cell. 2015 Sep 24;163(1):174-86.
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Cyclin-dependent kinase 7 inhibitor THZ2 inhibits the growth of human gastric cancer in vitro and in vivo.[Pubmed:30662617]
Am J Transl Res. 2018 Nov 15;10(11):3664-3676. eCollection 2018.
Cyclin-dependent kinase 7 (CDK7) is a member of the CDK family, which forms the CDK activating kinase complex with Cyclin H and RING finger protein Mat1 to control cell cycle progression and transcription by phosphorylating other CDKs and RNA polymerase II. In this study, we analyzed TCGA data and found that upregulation of CDK7 frequently occurred in human gastric cancer. A potent and selective irreversible CDK7 inhibitor THZ2 was able to induce cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the increasing intracellular reactive oxidative species (ROS) levels in gastric cancer cells. Pretreatment with ROS scavenger N-acety-L-cysteine partially reversed cell apoptosis induced by THZ2. In the nude mice, THZ2 also suppressed the growth of xenograft tumors of gastric cancer. Overall, our data showed that inhibition of CDK7 with THZ2 in gastric cancer presented outstanding anticancer effect in vitro and in vivo, suggesting that CDK7 is a potential therapeutic target for gastric cancer patients.
