Selective covalent CDK7 inhibitor THZ1 is a promising potential anti-tumor drug in many kinds of cancers. Epithelial-mesenchymal Transition (EMT) is highly related to cancer initiation, development, invasion and metastasis and other pathogenesis processes. We treated cancer cell line Hela229 and three...
From Structure Modification to Drug Launch: A Systematic Review of the Ongoing Development of Cyclin-Dependent Kinase Inhibitors for Multiple Cancer Therapy 2022, Journal of Medicinal Chemistry CDK7 Inhibitors in Cancer Therapy: The Sweet Smell of Success? 2020, Journal of Medicinal Chemistry Gambogic ...
[drug (μM)] 10 f 1 0.9 0.8 0.7 0.6 0.5 0.4 1 Log [THZ1(μM)] 0.1 1 0.9 0.8 0.7 0.6 0.5 0.4 1 0.1 Log [obatoclax (μM)] ALCL primary 4 3 2 1 0 Pre-THZ1 Post-THZ1 g OCI-Ly13.2 mice h OCI-Ly12 mice Day: 1 4.5 8 Day: 1 7 11 20 Vehicle Vehicle Obatoclax Oba...
The CDK7 inhibitors (CDK7i) ICEC0942 and THZ1, are promising new cancer therapeutics. Resistance to targeted drugs frequently compromises cancer treatment. We sought to identify mechanisms by which cancer cells may become resistant to CDK7i. Resistant lines were established through continuous drug se...
Therefore, THZ1 could be a potent drug for NSCLC and was used to investigate the functional role of CDK7 in NSCLC. First, THZ1 inhibited NSCLC viability in a time- and dose- dependent manner (Fig. 2a and S2C). Moreover, THZ1 treatment resulted in less and smaller colonies of NSCLC cell...
Drug resistanceApoptosisCell cyclemTOR inhibitorCDK7 cyclin-dependent kinase 7CTD carboxyl-terminal domainICI immune checkpoint inhibitormRCC metastatic RCCRCC renal cell carcinomaRenal cell carcinoma (RCC) is a major cancer of the kidney. The 5-year survival rate is overall 74% and only 8% for ...
In this study, we assessed the therapeutic potential of THZ1 as a promising drug candidate for the treatment of NSCLC. We found that THZ1 significantly inhibited proliferation of NSCLC cells and arrested the cell cycle in G2/M phase along with downregulation of cyclins and CDKs. Furthermore, ...
Moreover, in fast drug sensitivity assay, THZ1 and LY2228820 combination killed more lung adenocarcinoma cells from the PDX model than each drug alone (Fig. 4f). In addition, THZ1 and LY2228820 synergistically decreased the MYC protein and mRNA levels in A549 and H292 cells (Fig. 4g, h)....