| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
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| Targets |
CDK7 3.2 nM (IC50) CDK12 CDK13
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| ln Vitro |
At IC50 values of 50 nM and 0.55 nM, respectively, THZ1 hydrochloride inhibits both Jurkat and Loucy cells. CDK7 is time-dependently inhibited in vitro by THZ1 hydrochloride, and CDK7 is intracellularly bound by water molecule. Inhibiting CDK12, but at higher concentrations than CDK7, is THZ1 hydrochloride (9, 27, 83, 250, 750, and 2500 nM). Immediate RNAPII CTD and CAK phosphorylation inhibition is achieved by THZ1 hydrochloride (1 μM). A specific cysteine outside the CDK7 kinase domain in Hela S3 cells is covalently targeted by THZ1 hydrochloride (2.5 μM), which irreversibly inhibits RNAPII CTD phosphorylation. The administration of THZ1 Hydrochloride (250 nM) to T-ALL cell lines led to a reduction in anti-apoptotic proteins, specifically MCL-1 and XIAP, as well as an increase in apoptotic index and decreased cell proliferation [1]. The IC50 range for THZ1 Hydrochloride is 5–20 nM in all genotyped human (hSCLC) cell lines, indicating high sensitivity to the drug [3].
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| ln Vivo |
In vivo, THZ1 Hydrochloride (10 mg/kg) has strong antiproliferative action against primary TALL cells and human T-ALL xenografts, as well as strong killing of primary chronic lymphocytic leukemia (CLL) cells [1]. In a human MYCN-amplified NB mouse model, THZ1 hydrochloride (10 mg/kg, iv) reduced tumor growth while exhibiting no toxicity [4]. Without causing weight loss or other usual adverse effects, THZ1 Hydrochloride (10 mg/kg, ip) totally suppresses the formation of esophageal squamous cell carcinoma tumors in vivo [5].
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| References |
[1]. Kwiatkowski N, et al. Targeting transcription regulation in cancer with a covalent CDK7 inhibitor. Nature. 2014 Jul 31;511(7511):616-20.
[2]. Jiang YY, et al. Targeting super-enhancer-associated oncogenes in oesophageal squamous cell carcinoma. Gut. 2016 May 10. pii: gutjnl-2016-311818. [3]. Christensen CL, et al. Targeting transcriptional addictions in small cell lung cancer with a covalent CDK7 inhibitor. Cancer Cell. 2014 Dec 8;26(6):909-22. [4]. Chipumuro, et al. CDK7 inhibition suppresses super-enhancer-linked oncogenic transcription in MYCN-driven cancer. Cell. 2014 Nov 20;159(5):1126-39. ? |
| Molecular Formula |
C31H29CL2N7O2
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|---|---|
| Molecular Weight |
602.51
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| Related CAS # |
THZ1-R;1621523-07-6;THZ1;1604810-83-4
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| Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 :~22.5 mg/mL (~37.34 mM)
H2O :< 0.1 mg/mL |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.17 mg/mL (3.60 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 (3.60 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.17 mg/mL (3.60 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6597 mL | 8.2986 mL | 16.5972 mL | |
| 5 mM | 0.3319 mL | 1.6597 mL | 3.3194 mL | |
| 10 mM | 0.1660 mL | 0.8299 mL | 1.6597 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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