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| 25mg |
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Purity: ≥98%
THZ2, a THZ1 analog, is a novel, potent and selective CDK7 inhibitor with an IC50 of 13.9 nM. THZ2 can overcome THZ1's instability problem in vivo, and it may be used to treat triple-negative breast cancer (TNBC).
| Targets |
CDK7 (IC50 = 13.9 nM); CDK1 (IC50 = 96.9 nM); CDK2 (IC50 = 222 nM); CDK5 (IC50 = 134 nM); CDK9 (IC50 = 194 nM); CDK8 (IC50 = 6830 nM)
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| ln Vitro |
THZ2 potently suppresses triple-negative breast cancer cell growth while specifically targeting CDK7, leaving ER/PR+ cells unaffected. THZ2 effectively inhibits the clonogenic growth of TNBC cells at low nanomolar doses, with an IC50 of about 10 nM. In triple-negative breast cancer cells, but not in ER/PR+ breast cancer cells or normal human cells, THZ2 causes apoptotic cell death[1].
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| ln Vivo |
THZ2 (10 mg/Kg) exhibits anti-tumor activity and significantly slows the growth rate of tumors in mice. Tumor tissues isolated from mice treated with THZ2 exhibited decreased proliferation and increased apoptosis in comparison to vehicle-treated tumors, as demonstrated by immunostaining against Ki67 and cleaved Caspase 3, respectively. Body weight is decreased by THZ2 in NOD-SCID mice, indicating that THZ2 may not be as well tolerated in this specific strain of mice[1].
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| Cell Assay |
In the 96-well plate assay, cells are plated at a density of 2000 cells per well, and the following day, they are treated with different concentrations of THZ1 or THZ2. Cells are fixed and stained with crystal violet following a 48-hour incubation period. The staining is then removed by adding 10% acetic acid to each well, and the absorbance is measured at 590 nm using 750 nm as a reference.
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| Animal Protocol |
Mice: A single 400 rad dose of γ-irradiation is given to naked mice (CrTac:NCr-Foxn1nu) six hours prior to cell transplantation. The fourth pair of mice's mammary fat pads are injected with 100 μL of breast cancer cells per site after the cells are extracted and resuscitated in 40% Matrigel-Basement Membrane Matrix, LDEV-free. Manual calipers are used to measure tumors in two dimensions. The formula for calculating tumor volume is V=0.5× length× width× width. THZ2 (3 mg/mL, prepared in vehicle solutions) at a dose of 10 mg/kg intraperitoneally twice daily is administered to animals with established tumors (mean tumor volume of approximately 200 mm3), which are randomly divided into two groups and treated with vehicle (10% DMSO in D5W, 5% dextrose in water). Tumor volume is measured every two to three days. After being harvested, tumors are cut in half. One half is immediately snap frozen in liquid nitrogen for immunoblotting, and the other half is fixed in formalin for one night before being examined histopathologically and then in 70% ethanol.
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| References |
| Molecular Formula |
C31H28CLN7O2
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|---|---|
| Molecular Weight |
566.0527
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| Exact Mass |
565.20
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| Elemental Analysis |
C, 65.78; H, 4.99; Cl, 6.26; N, 17.32; O, 5.65
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| CAS # |
1604810-84-5
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| Related CAS # |
1604810-84-5
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| Appearance |
Solid powder
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| SMILES |
CN(C)C/C=C/C(=O)NC1=CC=CC(=C1)C(=O)NC2=CC=CC(=C2)NC3=NC=C(C(=N3)C4=CNC5=CC=CC=C54)Cl
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| InChi Key |
FONRCZUZCHXWBD-VGOFMYFVSA-N
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| InChi Code |
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+
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| 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
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| Synonyms |
THZ-2; THZ 2; THZ2
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (~176.7 mM)
Ethanol: ˂1 mg/mL (NaN mM) Water: ˂1 mg/mL (NaN mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.17 mg/mL (3.83 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.17 mg/mL (3.83 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7666 mL | 8.8331 mL | 17.6663 mL | |
| 5 mM | 0.3533 mL | 1.7666 mL | 3.5333 mL | |
| 10 mM | 0.1767 mL | 0.8833 mL | 1.7666 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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