1. Cell Cycle/DNA Damage
  2. CDK
  3. THZ1 Hydrochloride

THZ1 Hydrochloride is a selective and potent covalent CDK7 inhibitor with an IC50 of 3.2 nM. THZ1 Hydrochloride also inhibits the closely related kinases CDK12 and CDK13 and downregulates MYC expression.

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

THZ1 Hydrochloride Chemical Structure

THZ1 Hydrochloride Chemical Structure

Size Price Stock Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
USD 127 In-stock
Solution
10 mM * 1 mL in DMSO USD 127 In-stock
Solid
5 mg USD 96 In-stock
10 mg USD 168 In-stock
50 mg USD 550 In-stock
100 mg USD 850 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Customer Review

Based on 92 publication(s) in Google Scholar

Other Forms of THZ1 Hydrochloride:

Top Publications Citing Use of Products

80 Publications Citing Use of MCE THZ1 Hydrochloride

WB

    THZ1 Hydrochloride purchased from MedChemExpress. Usage Cited in: Acta Pharmacol Sin. 2019 Jun;40(6):814-822.  [Abstract]

    The protein expression levels of the genes related to cell cycle and metabolism are detected by immunoblotting using the corresponding antibodies in H1299 cells treated with 20 nM THZ1 alone or in combination with 500 nM CB-839 for 48 h.

    THZ1 Hydrochloride purchased from MedChemExpress. Usage Cited in: Oncogene. 2019 May;38(20):3932-3945.  [Abstract]

    Immunoblot analysis of the MYC and β-actin in cells (MiaPaCa2 and MiaPaCa2-R) treated with the indicated dose of THZ1 for 6 h.

    THZ1 Hydrochloride purchased from MedChemExpress. Usage Cited in: Onco Targets Ther. 2019 Mar 22;12:2137-2147.   [Abstract]

    Western blot is used to assess the RNA Pol II protein and its phosphorylation at serine 2, serine 5, and serine 7 in cervical cancer cells after treatment with the indicated concentrations of THZ1.

    THZ1 Hydrochloride purchased from MedChemExpress. Usage Cited in: Cell. 2018 Sep 20;175(1):171-185.e25.  [Abstract]

    WB analysis of MV4-11 cells treated with BTX161 (6 hr), iCDK9 (4 hr), or THZ1 (4 hr) at the indicated concentrations in different combinations as indicated. PP2Ac is a loading control.

    THZ1 Hydrochloride purchased from MedChemExpress. Usage Cited in: Nat Commun. 2018 Nov 19;9(1):4866.  [Abstract]

    MYCN, PHOX2B, and TBX2 protein levels 10 h and 16 h upon treatment with 1 μM JQ1, 35 nM THZ1 and the combination of JQ1 and THZ1 in the IMR-5/75 cell line.

    THZ1 Hydrochloride purchased from MedChemExpress. Usage Cited in: Nat Commun. 2018 Aug 23;9(1):3392.  [Abstract]

    21mers are synthesized in parallel reactions with unlabeled (upper panel) or radiolabeled (lower panel) ribonucleoside triphosphates in the presence of DMSO (-) or increasing amounts of THZ1; reactions are stopped after 15 or 60 min.

    THZ1 Hydrochloride purchased from MedChemExpress. Usage Cited in: Oncogenesis. 2017 May 15;6(5):e336.  [Abstract]

    Lysates from cells treated with vehicle or 200 nM THZ1 for 48 h analyzed for the activation status of multiple CDKs as indicated to the right of panels by western blotting.

    THZ1 Hydrochloride purchased from MedChemExpress. Usage Cited in: Mol Cancer Ther. 2017 Sep;16(9):1739-1750.  [Abstract]

    Western blot analysis of RNAPII CTD phosphorylation in ovarian cancer cells that are treated with THZ1.

    THZ1 Hydrochloride purchased from MedChemExpress. Usage Cited in: Mol Cancer Ther. 2017 Sep;16(9):1739-1750.  [Abstract]

    Western blot analysis of RNAPII CTD phosphorylation in ovarian cancer cells that are treated with THZ1.

    THZ1 Hydrochloride purchased from MedChemExpress. Usage Cited in: Mol Cancer Ther. 2017 Sep;16(9):1739-1750.  [Abstract]

    Western blot analysis of RNAPII CTD phosphorylation in ovarian cancer cells that are treated with THZ1.

    THZ1 Hydrochloride purchased from MedChemExpress. Usage Cited in: TUMOR, 2017, 37(11): 1119-1127.

    The expression level of cyclin-dependent kinase 7 (CDK7) and the phosphorylation level of RNA polymeraseⅡ carboxyl-terminal domain Ser-5 (RNAPolⅡS5) in ovarian cancer cells treated with THZ1 are detected by Western blotting. After the ovarian cancer IGROV1, OVCA433, SKOV3 and COV413B cells are treated with 0.5 μM THZ1 for 0, 4, 8, 12 and 24 h, the CDK7 expression and RNAPolⅡS5 phosphorylation levels are significantly down-regulated.

    THZ1 Hydrochloride purchased from MedChemExpress. Usage Cited in: Oncotarget. 2017 Apr 18;8(16):27353-27363.  [Abstract]

    Representative Western blot showing the phosphorylation status of ERα at serine 118 (S118) in MCF-7 cells in controls and after treatment with the CDK7 inhibitor, THZ1 (100 nM), or AG-490 (100 μM) for 3 h prior to E2 treatment for 30 min. Endogenous ERα and β-actin are used as loading controls.
    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    THZ1 Hydrochloride is a selective and potent covalent CDK7 inhibitor with an IC50 of 3.2 nM. THZ1 Hydrochloride also inhibits the closely related kinases CDK12 and CDK13 and downregulates MYC expression[1][2].

    IC50 & Target[1][2]

    CDK7

    3.2 nM (IC50)

    CDK12

     

    CDK13

     

    In Vitro

    THZ1 inhibits Jurkat cell and Loucy cell with IC50 of 50 nM, and 0.55 nM, respectively. THZ1 demonstrates time-dependent inhibition of CDK7 in vitro and covalent binding of intracellular CDK7. THZ1 (9, 27, 83, 250, 750, and 2500 nM) inhibits CDK12 but at higher concentrations compared to CDK7. THZ1 (1 μM) irreversibly inhibits RNAPII CTD and CAK phosphorylation. THZ1 (2.5 μM) irreversibly inhibits RNAPII CTD phosphorylation by covalently targeting a unique cysteine located outside the kinase domain of CDK7 in Hela S3 cells. THZ1 (250 nM) causes decreased cellular proliferation and an increase in apoptotic index with concomitant reduction in anti-apoptotic proteins, most notably MCL-1 and XIAP in T-ALL cell lines[1].
    ? All genotypically-distinct human (hSCLC) cell lines exhibit high sensitivity to THZ1, with an IC50 in the range of 5-20 nM[3].

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

    In Vivo

    THZ1 (10 mg/kg) demonstrates potent killing of primary chronic lymphocytic leukemia (CLL) cells and anti-proliferative activity against primary TALL cells and in vivo against a human T-ALL xenograft[1].
    ? THZ1 (10 mg/kg, i.v.) inhibits tumor growth in a mouse model of human MYCN-amplified NB and shows no toxicity[4].
    ? THZ1 (10 mg/kg, i.p.) completely suppresses oesophageal squamous cell carcinoma tumour growth in vivo without loss of body weight or other common toxic effects[5].

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

    Molecular Weight

    602.51

    Formula

    C31H29Cl2N7O2

    Appearance

    Solid

    Color

    White to yellow

    SMILES

    ClC1=CN=C(NC2=CC(NC(C3=CC=C(NC(/C=C/CN(C)C)=O)C=C3)=O)=CC=C2)N=C1C4=CNC5=CC=CC=C54.Cl

    Shipping

    Room temperature in continental US; may vary elsewhere.

    Storage

    4°C, sealed storage, away from moisture

    *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

    Solvent & Solubility
    In Vitro: 

    DMSO : 22.5 mg/mL (37.34 mM; Need ultrasonic and warming; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    H2O : < 0.1 mg/mL (insoluble)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 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
    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 (sealed storage, away from moisture). 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
    =
    Concentration
    ×
    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

    ×
    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: ≥ 2.17 mg/mL (3.60 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.17 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (21.7 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: 2.17 mg/mL (3.60 mM); Suspended solution; Need ultrasonic

      This protocol yields a suspended solution of 2.17 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 (21.7 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

    mg/kg

    Animal weight
    (per animal)

    g

    Dosing volume
    (per animal)

    μL

    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).

    *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

    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: 98.61%

    References
    Kinase Assay
    [1]

    For kinase assays following immunoprecipitation of FLAG-CDK7 protein from HCT116 or FLAG-CDK12 from 293A cellular lysates, cells are first treated with THZ1, THZ1-R, or DMSO for 4 hrs at 37°C. Cells are then harvested by lysis in 50 mM Tris HCl pH 8.0, 150 mM NaCl, 1% NP-40, 5 mM EDTA, and protease/phosphatase cocktails. Exogenous CDK7 or CDK12 proteins are immunoprecipitated from cellular lysates using FLAG antibody- conjugated agarose beads. Precipitated proteins are washed with lysis buffer 6 times, followed by 2 washes with kinase buffer (40 mM Hepes pH 7.5, 150 mM NaCl, 10 mM MgCl2, 5% glycerol) and subjected to in vitro kinase assays at 30°C for 45 minutes using 1 μg of the large subunit of RNAPII (RPB1) as substrate and 25 μM ATP and 10 μCi of 32P ATP. Note: no additional inhibitors are added to the kinase reaction mixture, therefore any inhibition results from the activity of the compounds that are added directly to cells (ie-intracellular inhibition). This suggests that the inhibitors are either covalently tethered to the kinase or have strong non-covalent character. Kinase assays using recombinant CDK7/TFIIH/MAT1 are conducted in the manner as described above using 25 ng of CAK complex per reaction. For kinase assays designed to test time-dependent inactivation of CDK7 kinase activity, CAK complex is pre-incubated with indicated concentrations of THZ1, THZ1-R, or DMSO in kinase buffer without ATP for 4 hrs at 30°C prior to being subjected to kinase assay conditions[1].

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

    Cell Assay
    [1]

    Jurkat, Loucy, KOPTK1, and DND-41 cell lines are seeded in 384-well microplates at 15% confluency in medium with 5% FBS and penicillin/streptavidin. Cells are treated with THZ1 (2, 10, 50, 250, 1250, and 6250 nM) or DMSO for 72 hrs and cell viability is determined using resazurin[1].

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

    Animal Administration
    [1]

    Mice[1]
    Thirty-two NOD-SCIDIL2Rcγnull (NSG) 9-week old female mice are divided into treatment groups based on mean BLI as follows: THZ1 10 mg/kg qD, THZ1 10 mg/kg BID, and vehicle (10% DMSO in D5W) BID (n=10 for all groups). Two mice are excluded, one with the highest and one with the lowest BLI. All treatments are administered via IV injection in the lateral tail vein in a volume of 3.3 μL/g (non-blinded). Mice are imaged and weighed every 3-5 days. Mice are treated for four weeks and on the final day mice are imaged, dosed and sacrificed approximately 5-6 hrs post dose. Upon sacrifice, blood is collected via cardiac puncture in EDTA tubes; a portion (300 uL) is processed for plasma. Liver and spleen tissues are collected from each mouse with half of each sample flash frozen and half of each sample fixed. Blood plasma and liver samples are processed for pharmacokinetics analysis of THZ1. Spleen tissues are homogenized and lysed and processed for pharmacodynamics analysis of THZ1 target engagement.

    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 (sealed storage, away from moisture). 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 1.6597 mL 8.2986 mL 16.5972 mL 41.4931 mL
    5 mM 0.3319 mL 1.6597 mL 3.3194 mL 8.2986 mL
    10 mM 0.1660 mL 0.8299 mL 1.6597 mL 4.1493 mL
    15 mM 0.1106 mL 0.5532 mL 1.1065 mL 2.7662 mL
    20 mM 0.0830 mL 0.4149 mL 0.8299 mL 2.0747 mL
    25 mM 0.0664 mL 0.3319 mL 0.6639 mL 1.6597 mL
    30 mM 0.0553 mL 0.2766 mL 0.5532 mL 1.3831 mL
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    • 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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