WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406560
CAS#: 1604810-83-4 (free base)
Description: THZ1 is a selective CDK7 inhibitor that preferentially diminishes transcription in cancer cells. THZ1 has the unprecedented ability to target a remote cysteine residue located outside of the canonical kinase domain, providing an unanticipated means of achieving selectivity for CDK7. Cancer cell-line profiling indicates that a subset of cancer cell lines, including human T-cell acute lymphoblastic leukaemia (T-ALL), have exceptional sensitivity to THZ1. Cyclin-dependent kinases (CDKs) are involved in temporal control of the cell cycle and transcription and play central roles in cancer development and metastasis.
MedKoo Cat#: 406560
Name: THZ1
CAS#: 1604810-83-4 (free base)
Chemical Formula: C31H28ClN7O2
Exact Mass: 565.1993
Molecular Weight: 566.05
Elemental Analysis: C, 65.78; H, 4.99; Cl, 6.26; N, 17.32; O, 5.65
Related CAS #: 1604810-83-4 (free base)
Synonym: THZ1; THZ1; THZ 1.
IUPAC/Chemical Name: (E)-N-(3-((5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)-4-(4-(dimethylamino)but-2-enamido)benzamide
InChi Key: OBJNFLYHUXWUPF-IZZDOVSWSA-N
InChi Code: InChI=1S/C31H28ClN7O2/c1-39(2)16-6-11-28(40)35-21-14-12-20(13-15-21)30(41)36-22-7-5-8-23(17-22)37-31-34-19-26(32)29(38-31)25-18-33-27-10-4-3-9-24(25)27/h3-15,17-19,33H,16H2,1-2H3,(H,35,40)(H,36,41)(H,34,37,38)/b11-6+
SMILES Code: O=C(NC1=CC=CC(NC2=NC=C(Cl)C(C3=CNC4=C3C=CC=C4)=N2)=C1)C5=CC=C(NC(/C=C/CN(C)C)=O)C=C5
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | THZ1 is a covalent CDK7 inhibitor with an IC50 of 3.2 nM and also inhibits the closely related kinases CDK12 and CDK13 and downregulates MYC expression. |
| In vitro activity: | In the present study, THZ1 arrested the cell cycle of B-ALL cells in vitro in a low concentration, while inducing the apoptosis of B-ALL cells in vitro in a high concentration by activating the apoptotic pathways. In addition, RNA-SEQ results revealed that THZ1 disrupted the cellular metabolic pathways of B-ALL cells. Moreover, THZ1 suppressed the cellular metabolism and blocked the production of cellular metabolic intermediates in B-ALL cells. Mechanistically, THZ1 inhibited the cellular metabolism of B-ALL by downregulating the expression of c-MYC-mediated metabolic enzymes, such as HK1, PFKP, PKM2, and LDHA. Reference: Front Oncol. 2021; 11: 663360. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056175/ |
| In vivo activity: | The brisk elevation of peritoneal CD11b+CD86+ cells, which was already distinct 12 h after LPS injection, was almost halved in mice pretreated with THZ1 (Fig. 2e, Fig. S2C). This phenomenon was further supported by the distribution and response of peritoneal macrophages, which changed markedly in pretreated mice with the decreased percentage of CD11b+F4/80+ macrophages (mean ± SD, LPS, 70.36 ± 6.284; THZ1+LPS, 43.32 ± 11.96) and inhibited transcription of inflammatory genes (Fig. 2f, g, Fig. S2C). A slight increase in CD11b+Ly6C+ monocytes (mean ± SD, LPS, 4.494 ± 3.192; THZ1+LPS, 15.53 ± 10.10) might be a secondary consequence of reduced macrophages. Collectively, the decrease and dysfunction of macrophages support the feasibility for controlling the magnitude of CRS and rescuing mice by blocking CDK7. Reference: Mol Cancer. 2021; 20: 5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780220/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 62.5 | 110.41 | |
| DMF | 30.0 | 53.0 | |
| DMF:PBS (pH 7.2) (1:2) | 0.3 | 0.53 |
The following data is based on the product molecular weight 566.05 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Abudureheman T, Xia J, Li MH, Zhou H, Zheng WW, Zhou N, Shi RY, Zhu JM, Yang LT, Chen L, Zheng L, Xue K, Qing K, Duan CW. CDK7 Inhibitor THZ1 Induces the Cell Apoptosis of B-Cell Acute Lymphocytic Leukemia by Perturbing Cellular Metabolism. Front Oncol. 2021 Apr 6;11:663360. doi: 10.3389/fonc.2021.663360. PMID: 33889549; PMCID: PMC8056175. 2. Attia YM, Shouman SA, Salama SA, Ivan C, Elsayed AM, Amero P, Rodriguez-Aguayo C, Lopez-Berestein G. Blockade of CDK7 Reverses Endocrine Therapy Resistance in Breast Cancer. Int J Mol Sci. 2020 Apr 23;21(8):2974. doi: 10.3390/ijms21082974. PMID: 32340192; PMCID: PMC7215326. 3. Wei Y, Li C, Bian H, Qian W, Jin K, Xu T, Guo X, Lu X, Su F. Targeting CDK7 suppresses super enhancer-linked inflammatory genes and alleviates CAR T cell-induced cytokine release syndrome. Mol Cancer. 2021 Jan 4;20(1):5. doi: 10.1186/s12943-020-01301-7. PMID: 33397398; PMCID: PMC7780220. 4. Kuo KL, Lin WC, Liu SH, Hsu FS, Kuo Y, Liao SM, Yang SP, Wang ZH, Hsu CH, Huang KH. THZ1, a covalent CDK7 inhibitor, enhances gemcitabine-induced cytotoxicity via suppression of Bcl-2 in urothelial carcinoma. Am J Cancer Res. 2021 Jan 1;11(1):171-180. PMID: 33520367; PMCID: PMC7840706. |
| In vitro protocol: | 1. Abudureheman T, Xia J, Li MH, Zhou H, Zheng WW, Zhou N, Shi RY, Zhu JM, Yang LT, Chen L, Zheng L, Xue K, Qing K, Duan CW. CDK7 Inhibitor THZ1 Induces the Cell Apoptosis of B-Cell Acute Lymphocytic Leukemia by Perturbing Cellular Metabolism. Front Oncol. 2021 Apr 6;11:663360. doi: 10.3389/fonc.2021.663360. PMID: 33889549; PMCID: PMC8056175. 2. Attia YM, Shouman SA, Salama SA, Ivan C, Elsayed AM, Amero P, Rodriguez-Aguayo C, Lopez-Berestein G. Blockade of CDK7 Reverses Endocrine Therapy Resistance in Breast Cancer. Int J Mol Sci. 2020 Apr 23;21(8):2974. doi: 10.3390/ijms21082974. PMID: 32340192; PMCID: PMC7215326. |
| In vivo protocol: | 1. Wei Y, Li C, Bian H, Qian W, Jin K, Xu T, Guo X, Lu X, Su F. Targeting CDK7 suppresses super enhancer-linked inflammatory genes and alleviates CAR T cell-induced cytokine release syndrome. Mol Cancer. 2021 Jan 4;20(1):5. doi: 10.1186/s12943-020-01301-7. PMID: 33397398; PMCID: PMC7780220. 2. Kuo KL, Lin WC, Liu SH, Hsu FS, Kuo Y, Liao SM, Yang SP, Wang ZH, Hsu CH, Huang KH. THZ1, a covalent CDK7 inhibitor, enhances gemcitabine-induced cytotoxicity via suppression of Bcl-2 in urothelial carcinoma. Am J Cancer Res. 2021 Jan 1;11(1):171-180. PMID: 33520367; PMCID: PMC7840706. |
1: Cao K, Shilatifard A. Inhibit Globally, Act Locally: CDK7 Inhibitors in Cancer Therapy. Cancer Cell. 2014 Aug 11;26(2):158-9. doi: 10.1016/j.ccr.2014.07.020. PubMed PMID: 25117707.
