THZ531
Based on 38 publication(s) in Google Scholar
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.
- Purity: 99.23%
- CAS No.: 1702809-17-3
- Formula: C30H32ClN7O2
- Molecular Weight:558.07
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Storage:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
Publications Citing Use of MedChemExpress (MCE) THZ531
More- Nature. 2020 Sep;585(7824):293-297. [Abstract]
- Cell. 2025 Oct 30;188(22):6301-6316.e29. [Abstract]
- Mol Cell. 2026 Feb 19;86(4):674-692.e10. [Abstract]
- Mol Cell. 2025 Nov 20;85(22):4166-4182.e10. [Abstract]
- Mol Cell. 2025 May 15;85(10):1952-1967.e8. [Abstract]
- Nat Commun. 2025 May 19;16(1):4656. [Abstract]
- Nat Chem Biol. 2020 Nov;16(11):1199-1207. [Abstract]
- Nucleic Acids Res. 2021 Apr 19;49(7):3748-3763. [Abstract]
- J Exp Clin Cancer Res. 2023 Aug 21;42(1):214. [Abstract]
- J Biomed Sci. 2022 Feb 14;29(1):13. [Abstract]
- Pharmacol Res. 2024 Mar:201:107097. [Abstract]
- Cell Death Dis. 2021 Jul 27;12(8):740. [Abstract]
- Cell Death Dis. 2020 Sep 15;11(9):754. [Abstract]
- EMBO J. 2025 Sep 8. [Abstract]
- Cell Rep. 2025 Nov 25;44(11):116495. [Abstract]
- J Med Chem. 2022 Jul 14;65(13):8881-8896. [Abstract]
- EMBO Rep. 2025 Jun;26(11):2836-2854. [Abstract]
- Eur J Med Chem. 2023 Nov 5:259:115648. [Abstract]
- Breast Cancer Res. 2023 May 5;25(1):51. [Abstract]
- Mol Oncol. 2024 May 22. [Abstract]
- J Cell Mol Med. 2026 Apr;30(7):e71101. [Abstract]
- iScience. 2024 May 16;27(6):110011. [Abstract]
- iScience. 2022 Aug 28;25(9):105030. [Abstract]
- Cell Signal. 2025 Dec 16:112328. [Abstract]
- Glycobiology. 2024 Dec 10;34(12):cwae081. [Abstract]
- Biochem Biophys Res Commun. 2024 Aug 28:735:150608. [Abstract]
- Biochem Biophys Res Commun. 2019 Dec 10;520(3):544-550. [Abstract]
- bioRxiv. 2026 Feb 20.
- Res Sq. 2025 Dec 18.
- bioRxiv. 2025 Nov 21:2025.11.20.689563. [Abstract]
- bioRxiv. 2025 March 19.
- bioRxiv. 2024 Dec 10:2024.12.09.627542. [Abstract]
- bioRxiv. 2023 Oct 22.
- bioRxiv. 2023 Jul 17.
- Patent. US20230124700A1.
- Harvard University. 2023 Mar. 30487357.
- bioRxiv. 2023 Mar 23.
- Universidade de Lisboa. 2021 Dec 21.
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Cell Proliferation/Viability Assay
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Cell Proliferation/Viability Assay
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RT-PCR
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IF
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Bio/Physico-chemical Assay
Biological Activity
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CDK12 158 nM (IC50) |
CDK13 69 nM (IC50) |
CDK7 8.5 μM (IC50) |
CDK9 10.5 μM (IC50) |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| Bel-7402 | IC50 |
650 nM
Compound: THZ531
|
Antiproliferative activity against human Bel-7402 cells assessed as inhibition of cell growth measured after 96 hrs by SRB assay
Antiproliferative activity against human Bel-7402 cells assessed as inhibition of cell growth measured after 96 hrs by SRB assay
|
[PMID: 36905918] |
| BT-474 | GI50 |
0.044 μM
Compound: THZ531
|
Antiproliferative activity against trastuzumab-sensitive HER2-positive human BT-474 cells by Cell Titer Glo assay
Antiproliferative activity against trastuzumab-sensitive HER2-positive human BT-474 cells by Cell Titer Glo assay
|
[PMID: 38061230] |
| HCT-116 | IC50 |
89 nM
Compound: THZ531
|
Antiproliferative activity against human HCT-116 cells assessed as inhibition of cell growth measured after 96 hrs by SRB assay
Antiproliferative activity against human HCT-116 cells assessed as inhibition of cell growth measured after 96 hrs by SRB assay
|
[PMID: 36905918] |
| HeLa | IC50 |
106 nM
Compound: THZ531
|
Antiproliferative activity against human HeLa cells assessed as inhibition of cell growth measured after 96 hrs by SRB assay
Antiproliferative activity against human HeLa cells assessed as inhibition of cell growth measured after 96 hrs by SRB assay
|
[PMID: 36905918] |
| JIMT-1 | GI50 |
1.84 μM
Compound: THZ531
|
Antiproliferative activity against trastuzumab-resistant HER2-positive human JIMT-1 cells by Cell Titer Glo assay
Antiproliferative activity against trastuzumab-resistant HER2-positive human JIMT-1 cells by Cell Titer Glo assay
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[PMID: 38061230] |
| Kelly | IC50 |
253.8 nM
Compound: 10a; THZ531
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Antiproliferative activity against human Kelly cells harboring CDK12 C1039F mutant assessed as reduction in cell viability incubated for 72 hrs by CellTiter-Glo assay
Antiproliferative activity against human Kelly cells harboring CDK12 C1039F mutant assessed as reduction in cell viability incubated for 72 hrs by CellTiter-Glo assay
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[PMID: 33945934] |
| Kelly | IC50 |
93 nM
Compound: 10a; THZ531
|
Antiproliferative activity against human Kelly cells harboring wild type CDK12 assessed as reduction in cell viability incubated for 72 hrs by CelTiter-Glo assay
Antiproliferative activity against human Kelly cells harboring wild type CDK12 assessed as reduction in cell viability incubated for 72 hrs by CelTiter-Glo assay
|
[PMID: 33945934] |
| L02 | IC50 |
119 nM
Compound: THZ531
|
Cytotoxicity against human L02 cells assessed as inhibition of cell growth measured after 96 hrs by SRB assay
Cytotoxicity against human L02 cells assessed as inhibition of cell growth measured after 96 hrs by SRB assay
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[PMID: 36905918] |
| MDA-MB-231 | IC50 |
133 nM
Compound: THZ531
|
Antiproliferative activity against human MDA-MB-231 cells assessed as inhibition of cell growth measured after 96 hrs by SRB assay
Antiproliferative activity against human MDA-MB-231 cells assessed as inhibition of cell growth measured after 96 hrs by SRB assay
|
[PMID: 36905918] |
| MDA-MB-231 | IC50 |
17.9 μM
Compound: 13; THZ531
|
Antiproliferative activity against human MDA-MB-231 cells assessed as inhibition of cell growth incubated for 48 hrs by MTT assay
Antiproliferative activity against human MDA-MB-231 cells assessed as inhibition of cell growth incubated for 48 hrs by MTT assay
|
[PMID: 37478560] |
| MDA-MB-231 | IC50 |
7.1 μM
Compound: 13; THZ531
|
Antiproliferative activity against human MDA-MB-231 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
Antiproliferative activity against human MDA-MB-231 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
|
[PMID: 37478560] |
| MDA-MB-436 | IC50 |
18.1 μM
Compound: 13; THZ531
|
Antiproliferative activity against human MDA-MB-436 cells assessed as inhibition of cell growth incubated for 48 hrs by MTT assay
Antiproliferative activity against human MDA-MB-436 cells assessed as inhibition of cell growth incubated for 48 hrs by MTT assay
|
[PMID: 37478560] |
| MDA-MB-436 | IC50 |
6.4 μM
Compound: 13; THZ531
|
Antiproliferative activity against human MDA-MB-436 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
Antiproliferative activity against human MDA-MB-436 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
|
[PMID: 37478560] |
| MDA-MB-468 | IC50 |
14.4 μM
Compound: 13; THZ531
|
Antiproliferative activity against human MDA-MB-468 cells assessed as inhibition of cell growth incubated for 48 hrs by MTT assay
Antiproliferative activity against human MDA-MB-468 cells assessed as inhibition of cell growth incubated for 48 hrs by MTT assay
|
[PMID: 37478560] |
| MDA-MB-468 | IC50 |
5.8 μM
Compound: 13; THZ531
|
Antiproliferative activity against human MDA-MB-468 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
Antiproliferative activity against human MDA-MB-468 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
|
[PMID: 37478560] |
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.
Chemical Information
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CAS No. 1702809-17-3
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Appearance Solid
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Molecular Weight 558.07
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Formula C30H32ClN7O2
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Color White to light yellow
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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
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Publications (38)
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Journal Impact Factor
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Most Recent
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Nature
2020 Sep;585(7824):293-297. PMID: 32494016
THZ531 purchased from MedChemExpress. Usage Cited in: Nature. 2020 Sep;585(7824):293-297. [Abstract]
Titration of CDK12-Alexa488cycK (0-3.75 μM) to 50 nM terbiumDDB1 in the presence of 5 μM THZ531, ATP or DMSO.
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Cell
2025 Oct 30;188(22):6301-6316.e29. PMID: 40818455 -
Mol Cell
HSPA1A and DNAJB1 regulate NELF condensate dynamics to safeguard transcriptional recovery under heat stress. [Abstract]2026 Feb 19;86(4):674-692.e10. PMID: 41653920 -
Mol Cell
A role for human senataxin in contending with pausing and backtracking during transcript elongation. [Abstract]2025 Nov 20;85(22):4166-4182.e10. PMID: 41232527 -
Mol Cell
PAF1C-mediated activation of CDK12/13 kinase activity is critical for CTD phosphorylation and transcript elongation. [Abstract]2025 May 15;85(10):1952-1967.e8. PMID: 40315851 -
Nat Commun
Transcriptional and epigenetic rewiring by the NUP98::KDM5A fusion oncoprotein directly activates CDK12. [Abstract]2025 May 19;16(1):4656. PMID: 40389480
THZ531 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2025 May 19;16(1):4656. [Abstract]
Cell viability assay of primary human NUP98-rearranged AML cells, healthy donor BM MNC and CD34+ progenitors treated with indicated concentrations of THZ531 (0.1 nM-10 μM) for 3 days.
THZ531 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2025 May 19;16(1):4656. [Abstract]
GI50 values from cell viability assays of murine AML cells treated with THZ531 for 3 days.
THZ531 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2025 May 19;16(1):4656. [Abstract]
RT-qPCR analysis of dTAG-NUP98::KDM5A cells treated with THZ531 (2 µM, 24 h) showing log2FC values.
THZ531 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2025 May 19;16(1):4656. [Abstract]
Representative images of γH2A.X immunofluorescence staining of dTAG-GFP-NUP98::KDM5A cells treated with THZ531 (2 µM, 24 h) (left) and quantification of γH2A.x signal (right). Midline represents the median, bounds of the box represent the inter-quartile range (Q1 to Q3), and whiskers represent minimum and maximum values.
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Nat Chem Biol
2020 Nov;16(11):1199-1207. PMID: 32747809 -
Nucleic Acids Res
Interaction of the NRF2 and p63 transcription factors promotes keratinocyte proliferation in the epidermis. [Abstract]2021 Apr 19;49(7):3748-3763. PMID: 33764436 -
J Exp Clin Cancer Res
MYC up-regulation confers vulnerability to dual inhibition of CDK12 and CDK13 in high-risk Group 3 medulloblastoma. [Abstract]2023 Aug 21;42(1):214. PMID: 37599362 -
J Biomed Sci
O-GlcNAc transferase couples MRE11 to transcriptionally active chromatin to suppress DNA damage. [Abstract]2022 Feb 14;29(1):13. PMID: 35164752 -
Pharmacol Res
CDK12 inhibition upregulates ATG7 triggering autophagy via AKT/FOXO3 pathway and enhances anti-PD-1 efficacy in colorectal cancer. [Abstract]2024 Mar:201:107097. PMID: 38354870 -
Cell Death Dis
2021 Jul 27;12(8):740. PMID: 34315855 -
Cell Death Dis
2020 Sep 15;11(9):754. PMID: 32934219 -
EMBO J
Resistance to CDK7 inhibitors directed by acquired mutation of a conserved residue in cancer cells. [Abstract]2025 Sep 8. PMID: 40921851 -
Cell Rep
CDK12 inhibition reveals melanoma dependence on the RUNX1/CBFβ complex for genomic stability. [Abstract]2025 Nov 25;44(11):116495. PMID: 41176765 -
J Med Chem
3,5,7-Substituted Pyrazolo[4,3- d]Pyrimidine Inhibitors of Cyclin-Dependent Kinases and Cyclin K Degraders. [Abstract]2022 Jul 14;65(13):8881-8896. PMID: 35749742 -
EMBO Rep
DDB1 engagement defines the selectivity of S656 analogs for cyclin K degradation over CDK inhibition. [Abstract]2025 Jun;26(11):2836-2854. PMID: 40295725 -
Eur J Med Chem
Discovery of a novel dual-target inhibitor of CDK12 and PARP1 that induces synthetic lethality for treatment of triple-negative breast cancer. [Abstract]2023 Nov 5:259:115648. PMID: 37478560 -
Breast Cancer Res
Systematic screening identifies ABCG2 as critical factor underlying synergy of kinase inhibitors with transcriptional CDK inhibitors. [Abstract]2023 May 5;25(1):51. PMID: 37147730 -
Mol Oncol
2024 May 22. PMID: 38775167 -
J Cell Mol Med
2026 Apr;30(7):e71101. PMID: 41896195 -
iScience
Transcriptional synergy in human aortic endothelial cells is vulnerable to combination p300/CBP and BET bromodomain inhibition. [Abstract]2024 May 16;27(6):110011. PMID: 38868181 -
iScience
2022 Aug 28;25(9):105030. PMID: 36111258 -
Cell Signal
Targeting CDK12 rescues C/EBPβ-mediated platinum and PARP inhibitor resistance in ovarian cancer. [Abstract]2025 Dec 16:112328. PMID: 41412562 -
Glycobiology
Compromised CDK12 activity causes dependency on the high activity of O-GlcNAc transferase. [Abstract]2024 Dec 10;34(12):cwae081. PMID: 39361894 -
Biochem Biophys Res Commun
Interaction of CDK12 with NXF1 is a new node for the linking mechanism between transcription and transportation of mRNA. [Abstract]2024 Aug 28:735:150608. PMID: 39270556 -
Biochem Biophys Res Commun
2019 Dec 10;520(3):544-550. PMID: 31615655 -
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bioRxiv
2025 Nov 21:2025.11.20.689563. PMID: 41332615 -
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bioRxiv
2024 Dec 10:2024.12.09.627542. PMID: 39713309 -
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Solvent & Solubility
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)
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.
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.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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.
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.
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.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
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).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
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.
Protocol
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (273 KB)
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SDS (643 KB)
- English - EN (643 KB)
- Français - FR (643 KB)
- Deutsch - DE (643 KB)
- Norwegian - NO (643 KB)
- Español - ES (643 KB)
- Swedish - SV (643 KB)
- Italian - IT (643 KB)
- Korean - KR (643 KB)
- Portuguese - PT (643 KB)
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Handling Instructions (2659 KB)
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 |