Accueil>>Signaling Pathways>> DNA Damage/DNA Repair>> CDK>>THZ2

THZ2

Catalog No.GC13511

THZ2 est un inhibiteur puissant et sélectif de CDK7 avec une IC50 de 13,9 nM.

Products are for research use only. Not for human use. We do not sell to patients.

THZ2 Chemical Structure

Cas No.: 1604810-84-5

Taille Prix Stock Qté
10mM (in 1mL DMSO)
534,00 $US
En stock
5mg
258,00 $US
En stock
10mg
361,00 $US
En stock
50mg
1 075,00 $US
En stock
100mg
1 445,00 $US
En stock

Tel:(909) 407-4943 Email: sales@glpbio.com

Avis des clients

Based on customer reviews.

  • GlpBio Citations

    GlpBio Citations
  • Bioactive Compounds Premium Provider

    Bioactive Compounds Premium Provider

Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

View current batch:

Protocol

Cell experiment [1]:

Cell lines

TNBC cells

Preparation method

The solubility of this compound in DMSO is > 28.3 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months.

Reacting condition

0.1 ~ 10000 nM; 7 days

Applications

At low nanomolar doses, THZ2 efficiently suppressed the cell growth of TNBC cells (IC50 = ~ 10 nM). Besides, THZ2 also induced apoptotic cell death in triple-negative, but not ER/PR+, breast cancer cells or normal human cells. Meanwhile, THZ2 did not elicit an obvious alteration in cell cycle.

Animal experiment [2]:

Animal models

Nude mice bearing triple-negative breast tumors

Dosage form

10 mg/kg; i.p.; 50 hrs or 25 days

Applications

In nude mice bearing triple-negative breast tumors, THZ2 significantly reduced the growth rate of tumors without affecting body weight. Moreover, both acute (50 hrs) and chronic exposure (25 days) to THZ2 substantially reduced CTD phosphorylation of RNAPII at all 3 phosphorylation sites (i.e. S2, S5 and S7), which indicated that CDK7 was efficiently inhibited in the tumor cells. According to the immunostaining analysis results of tumor tissues isolated from mice treated with THZ2, reduced proliferation and increased apoptosis were observed.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[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.

Background

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.

Chemical Properties

Cas No. 1604810-84-5 SDF
Chemical Name (Z)-N-(3-((5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)-3-((Z)-((E)-4-(dimethylamino)-1-hydroxybut-2-en-1-ylidene)amino)benzimidic acid
Canonical SMILES CN(C/C([H])=C([H])/C(O)=N/C1=CC=CC(/C(O)=N/C2=CC(NC3=NC=C(Cl)C(C4=CNC5=CC=CC=C45)=N3)=CC=C2)=C1)C
Formula C31H28ClN7O2 M.Wt 566.05
Solubility ≥ 28.3mg/mL in DMSO Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
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
  • Molarity Calculator

  • Dilution Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
**When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / CoA (available online).

Calculate

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.

Avis

Review for THZ2

Average Rating: 5 ★★★★★ (Based on Reviews and 16 reference(s) in Google Scholar.)

5 Star
100%
4 Star
0%
3 Star
0%
2 Star
0%
1 Star
0%
Review for THZ2

GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.

Required fields are marked with *

You may receive emails regarding this submission. Any emails will include the ability to opt-out of future communications.