1. Cell Cycle/DNA Damage
  2. CDK
  3. THZ531

THZ531 est un inhibiteur sélectif et covalent des CDK12 et CDK13 avec des IC50 de 158 nM et 69 nM , respectivement.

THZ531 is a selective and covalent inhibitor of both CDK12 and CDK13 with IC50s of 158 nM and 69 nM, respectively.

For research use only. We do not sell to patients.

THZ531 Chemical Structure

THZ531 Chemical Structure

CAS No. : 1702809-17-3

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1 mg USD 80 In-stock
5 mg USD 140 In-stock
10 mg USD 190 In-stock
25 mg USD 420 In-stock
50 mg USD 660 In-stock
100 mg USD 880 In-stock
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Based on 21 publication(s) in Google Scholar

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  • Protocol

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  • References

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Description

THZ531 is a selective and covalent inhibitor of both CDK12 and CDK13 with IC50s of 158 nM and 69 nM, respectively[1].

IC50 & Target[1]

CDK12

158 nM (IC50)

CDK13

69 nM (IC50)

CDK7

8.5 μM (IC50)

CDK9

10.5 μM (IC50)

In Vitro

The results from Kinase assays demonstrate that THZ531 potently inhibits CDK12 and CDK13 with IC50s of 158 nM and 69 nM, respectively; whereas inhibition of CDK7 and CDK9 is more than 50-fold weaker with IC50s of 8.5 and 10.5 μM, respectively. THZ531 treatment leads to a dramatic and irreversible decrease in Jurkat cell proliferation with an IC50 of 50 nM. FACS cell cycle analysis following treatment with escalating doses of THZ531 displays a dose and time-dependent increase in the number of cells exhibiting sub-G1 content. At 50 nM THZ531, no increase in the percentage of apoptotic cells is observed over DMSO control for the time course of the experiment. Higher doses of THZ531 leads to pronounced Annexin V signal with 30 to 40% annexin V-positively stained cells by 72 hrs. A dramatic reduction in elongating Pol II following THZ531 treatment is also observed[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Molecular Weight

558.07

Formula

C30H32ClN7O2

CAS No.
Appearance

Solid

Color

White to light yellow

SMILES

ClC(C(C1=CNC2=CC=CC=C12)=N3)=CN=C3N[C@@H]4CCCN(C(C5=CC=C(NC(/C=C/CN(C)C)=O)C=C5)=O)C4

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 250 mg/mL (447.97 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.7919 mL 8.9594 mL 17.9189 mL
5 mM 0.3584 mL 1.7919 mL 3.5838 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
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Concentration
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Volume
×
Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

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Volume (final)

V2

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 1.43 mg/mL (2.56 mM); Clear solution

    This protocol yields a clear solution of ≥ 1.43 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (14.3 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: 1.43 mg/mL (2.56 mM); Suspended solution; Need ultrasonic

    This protocol yields a suspended solution of 1.43 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (14.3 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

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Animal weight
(per animal)

g

Dosing volume
(per animal)

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Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation

Purity: 99.86%

References
Kinase Assay
[1]

Cells are treated with THZ531 or DMSO for 6 hrs. Following treatment cells are washed 2-fold with cold PBS and then lysed in the following lysis buffer: 50 mM Hepes pH 7.4, 150 mM NaCl, 1% Nonidet P40 substitute, 5 mM EDTA, 1 mM DTT, and protease/phosphatase cocktails. Following clearance, lysates are treated with bio-THZ1 or bio-TH531 for pulldown overnight at 4°C. Lysates are further incubated at room temperature for 3 hrs to increase the efficiency of covalent bond formation. Lysates are then incubated with streptavidin agarose for pulldown for an additional 2 to 3 hrs at 4°C[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[1]

Jurkat cells are plated in 96-well plates at 20,000 cells/well in fresh media and treated with THZ531 or DMSO at the indicated concentrations for 72 hours. HAP1 cells are seeded in 96-well plates at 12,000 cells/well in fresh media and 24 hours later are treated with THZ531 at the indicated concentrations for 72 hours. Anti-proliferative effect of THZ531 is assessed. To assess the effect of inhibitor washout on anti-proliferation of Jurkat cells, cells are treated with THZ531 or DMSO for 6 hrs. Inhibitor-containing medium is then removed and incubated with or without THZ531 for 66 hrs. Anti-proliferative effect of THZ531 is assessed. All proliferation assays are performed in biological triplicate. IC50s are determined using non-linear regression curve fit[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 1.7919 mL 8.9594 mL 17.9189 mL 44.7972 mL
5 mM 0.3584 mL 1.7919 mL 3.5838 mL 8.9594 mL
10 mM 0.1792 mL 0.8959 mL 1.7919 mL 4.4797 mL
15 mM 0.1195 mL 0.5973 mL 1.1946 mL 2.9865 mL
20 mM 0.0896 mL 0.4480 mL 0.8959 mL 2.2399 mL
25 mM 0.0717 mL 0.3584 mL 0.7168 mL 1.7919 mL
30 mM 0.0597 mL 0.2986 mL 0.5973 mL 1.4932 mL
40 mM 0.0448 mL 0.2240 mL 0.4480 mL 1.1199 mL
50 mM 0.0358 mL 0.1792 mL 0.3584 mL 0.8959 mL
60 mM 0.0299 mL 0.1493 mL 0.2986 mL 0.7466 mL
80 mM 0.0224 mL 0.1120 mL 0.2240 mL 0.5600 mL
100 mM 0.0179 mL 0.0896 mL 0.1792 mL 0.4480 mL
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THZ531 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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