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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C31H30Cl3N7O2 |
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分子量 | 638.97 | CAS No. | 2095433-94-4 | ||||
Solubility (25°C)* | 体外 | DMSO | 100 mg/mL (156.5 mM) | ||||
Water | Insoluble | ||||||
Ethanol | Insoluble | ||||||
体内 (毎回新しく調製した物を用意してください) |
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | THZ1 is a covalent CDK7 inhibitor which 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. |
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in vitro | THZ1 uses a unique mechanism, combining ATP-site and allosteric covalent binding, as a means of attaining potency and selectivity for CDK7. THZ1 irreversibly inhibits RNAPII CTD phosphorylation by covalently targeting a unique cysteine located outside the kinase domain of CDK7. THZ1, but not THZ1-R, completely inhibits the phosphorylation of the established intracellular CDK7 substrate RNAPII CTD at Ser 5 and Ser 7, with concurrent loss of Ser 2 phosphorylation at 250 nM in Jurkat cells. THZ1 exhibits strong antiproliferative effects across a broad range of cancer cell lines from various cancer types. In Jurkat cells, low-dose THZ1 has a profound effect on a small subset of genes, including the key regulator RUNX1, thus contributing to subsequent loss of the greater gene expression program and cell death[1]. THZ1 causes defects in Pol II(polymerase II) phosphorylation, co-transcriptional capping, promoter proximal pausing, and productive elongation[2]. |
in vivo | THZ1 reduces the proliferation of KOPTK1 T-ALL cells in a human xenograft mouse model. THZ1 is well tolerated at 10 mg/kg with no observable body weight loss or behavioural changes, suggesting that it causes no overt toxicity in the animals[1]. |
細胞アッセイ | 細胞株 | Jurkat, Loucy, KOPTK1 and DND-41 cell lines |
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濃度 | 0-10 μM | |
反応時間 | 4 h | |
実験の流れ | Cells are treated with THZ1, THZ1-R or dimethylsulphoxide (DMSO) for 0-6 h to assess the effect of time on the THZ1-mediated inhibition of RNAPII CTD phosphorylation. For subsequent experiments cells are treated with compounds for 4 h as determined by the time-course experiment described earlier, unless otherwise noted. For inhibitor washout experiments, cells are treated with THZ1, THZ1-R or DMSO for 4 h. Medium containing inhibitors is subsequently removed to effectively 'washout' the compound and the cells are allowed to grow in the absence of inhibitor. For each experiment, lysates are probed for RNAPII CTD phosphorylation and other specified proteins. | |
動物実験 | 動物モデル | Bioluminescent xenografted mouse model |
投薬量 | 10 mg/kg | |
投与方法 | i.v. |
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Data from [Data independently produced by , , J Cancer, 2018, 9(17):3149-3155]
Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation [ Nat Commun, 2024, 15(1):2089] | PubMed: 38453961 |
CDK7-YAP-LDHD axis promotes D-lactate elimination and ferroptosis defense to support cancer stem cell-like properties [ Signal Transduct Target Ther, 2023, 8(1):302] | PubMed: 37582812 |
Targeting transcriptional kinase of CDK7 halts proliferation of multiple myeloma cells by modulating the function of canonical NF-kB pathway and cell cycle regulatory proteins [ Transl Oncol, 2023, 35:101729] | PubMed: 37369156 |
Chemo-phosphoproteomic profiling with ATR inhibitors berzosertib and gartisertib uncovers new biomarkers and DNA damage response regulators [ bioRxiv, 2023, 10.1101/2023.04.03.535285] | PubMed: none |
Rewiring of master transcription factor cistromes during high-grade serous ovarian cancer development [ bioRxiv, 2023, 2023.04.11.536378] | PubMed: 37090516 |
STREAMING-tag system reveals spatiotemporal relationships between transcriptional regulatory factors and transcriptional activity [ Nat Commun, 2022, 13(1):7672] | PubMed: 36539402 |
CDK7/12/13 inhibition targets an oscillating leukemia stem cell network and synergizes with venetoclax in acute myeloid leukemia [ EMBO Mol Med, 2022, e14990] | PubMed: 35253392 |
Targeting dual oncogenic machineries driven by TAL1 and PI3K-AKT pathways in Tcell acute lymphoblastic leukemia [ Haematologica, 2022, 10.3324/haematol.2022.280761] | PubMed: 36073513 |
Systematic illumination of druggable genes in cancer genomes [ Cell Rep, 2022, 38(8):110400] | PubMed: 35196490 |
Combined inhibition of EZH2 and ATM is synthetic lethal in BRCA1-deficient breast cancer [ Breast Cancer Res, 2022, 24(1):41] | PubMed: 35715861 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。