CDK inhibitors in cancer therapy, an overview of recent development

M Zhang, L Zhang, R Hei, X Li, H Cai… - American journal of …, 2021‏ - pmc.ncbi.nlm.nih.gov
Dysregulated cell division, which leads to aberrant cell proliferation, is one of the key
hallmarks of cancer. Therefore, therapeutic targets that block cell division would be effective …

CDK7 inhibitors as anticancer drugs

GP Sava, H Fan, RC Coombes, L Buluwela… - Cancer and Metastasis …, 2020‏ - Springer
Abstract Cyclin-dependent kinase 7 (CDK7), along with cyclin H and MAT1, forms the CDK-
activating complex (CAK), which directs progression through the cell cycle via T-loop …

High-resolution cryo-EM of the human CDK-activating kinase for structure-based drug design

VI Cushing, AF Koh, J Feng, K Jurgaityte… - Nature …, 2024‏ - nature.com
Rational design of next-generation therapeutics can be facilitated by high-resolution
structures of drug targets bound to small-molecule inhibitors. However, application of …

CDK7 inhibition suppresses super-enhancer-linked oncogenic transcription in MYCN-driven cancer

E Chipumuro, E Marco, CL Christensen, N Kwiatkowski… - Cell, 2014‏ - cell.com
The MYC oncoproteins are thought to stimulate tumor cell growth and proliferation through
amplification of gene transcription, a mechanism that has thwarted most efforts to inhibit …

Targeting cell-cycle machinery in cancer

JM Suski, M Braun, V Strmiska, P Sicinski - Cancer cell, 2021‏ - cell.com
Abnormal activity of the core cell-cycle machinery is seen in essentially all tumor types and
represents a driving force of tumorigenesis. Recent studies revealed that cell-cycle proteins …

RNA cytosine methylation and methyltransferases mediate chromatin organization and 5-azacytidine response and resistance in leukaemia

JX Cheng, L Chen, Y Li, A Cloe, M Yue, J Wei… - Nature …, 2018‏ - nature.com
The roles of RNA 5-methylcytosine (RNA: m5C) and RNA: m5C methyltransferases (RCMTs)
in lineage-associated chromatin organization and drug response/resistance are unclear …

[HTML][HTML] Development of a selective CDK7 covalent inhibitor reveals predominant cell-cycle phenotype

CM Olson, Y Liang, A Leggett, WD Park, L Li… - Cell chemical …, 2019‏ - cell.com
Summary Cyclin-dependent kinase 7 (CDK7) regulates both cell cycle and transcription, but
its precise role remains elusive. We previously described THZ1, a CDK7 inhibitor, which …

Genomic modelling of the ESR1 Y537S mutation for evaluating function and new therapeutic approaches for metastatic breast cancer

A Harrod, J Fulton, VTM Nguyen, M Periyasamy… - Oncogene, 2017‏ - nature.com
Drugs that inhibit estrogen receptor-α (ER) activity have been highly successful in treating
and reducing breast cancer progression in ER-positive disease. However, resistance to …

Quantifying CDK inhibitor selectivity in live cells

CI Wells, JD Vasta, CR Corona, J Wilkinson… - Nature …, 2020‏ - nature.com
Concerted multidisciplinary efforts have led to the development of Cyclin-Dependent Kinase
inhibitors (CDKi's) as small molecule drugs and chemical probes of intracellular CDK …

ICEC0942, an orally bioavailable selective inhibitor of CDK7 for cancer treatment

H Patel, M Periyasamy, GP Sava… - Molecular cancer …, 2018‏ - aacrjournals.org
Recent reports indicate that some cancer types are especially sensitive to transcription
inhibition, suggesting that targeting the transcriptional machinery provides new approaches …