CDK8 and CDK19: positive regulators of signal-induced transcription and negative regulators of Mediator complex proteins

M Chen, J Li, L Zhang, L Wang, C Cheng… - Nucleic Acids …, 2023 - academic.oup.com
We have conducted a detailed transcriptomic, proteomic and phosphoproteomic analysis of
CDK8 and its paralog CDK19, alternative enzymatic components of the kinase module …

Inhibition of CDK8/19 Mediator kinase potentiates HER2-targeting drugs and bypasses resistance to these agents in vitro and in vivo

X Ding, AC Sharko, MSJ McDermott… - Proceedings of the …, 2022 - National Acad Sciences
Breast cancers (BrCas) that overexpress oncogenic tyrosine kinase receptor HER2 are
treated with HER2-targeting antibodies (such as trastuzumab) or small-molecule kinase …

Mediator kinase inhibition reverses castration resistance of advanced prostate cancer

J Li, TA Hilimire, Y Liu, L Wang, J Liang… - The Journal of …, 2024 - Am Soc Clin Investig
Mediator kinases CDK19 and CDK8, pleiotropic regulators of transcriptional reprogramming,
are differentially regulated by androgen signaling, but both kinases are upregulated in …

[HTML][HTML] The study of a novel CDK8 inhibitor E966-0530–45418 that inhibits prostate cancer metastasis in vitro and in vivo

TY Ho, TY Sung, SL Pan, WJ Huang, KC Hsu… - Biomedicine & …, 2023 - Elsevier
Prostate cancer is a prevalent malignancy among men globally, and androgen deprivation
therapy is the conventional first-line treatment for metastatic prostate cancer. While …

Unveiling the impact of CDK8 on tumor progression: mechanisms and therapeutic strategies

X Yin, Z He, K Chen, K Ouyang, C Yang, J Li… - Frontiers in …, 2024 - frontiersin.org
CDK8 is an important member of the cyclin-dependent kinase family associated with
transcription and acts as a key “molecular switch” in the Mediator complex. CDK8 regulates …

[HTML][HTML] Design, synthesis, and biological evaluation of indolin-2-one derivatives as novel cyclin-dependent protein kinase 8 (CDK8) inhibitors

JY Hsu, KC Hsu, C Sun, CH Chou, TE Lin… - Biomedicine & …, 2023 - Elsevier
Cyclin-dependent protein kinase 8 (CDK8) plays important roles in regulating fibrotic growth
factors and inflammatory signaling pathways. Long-term chronic inflammation of the lungs …

Mediator kinase inhibitors suppress triple-negative breast cancer growth and extend tumor suppression by mTOR and AKT inhibitors

X Ding, J Liang, AC Sharko, TA Hilimire, J Li… - Proceedings of the …, 2024 - pnas.org
Triple-negative breast cancers (TNBC) are treated primarily by chemotherapy and lack
clinically validated therapeutic targets. In particular, inhibitors of the PI3K/AKT/mTOR …

Cu-Catalyzed Decarboxylative Annulation of N-Phenylglycines with Maleimides: Synthesis of 1H-Pyrrolo[3,4-c]quinoline-1,3(2H)-diones

KH Lv, L Chen, K Zhao, JM Yang… - The Journal of Organic …, 2023 - ACS Publications
A novel protocol for the construction of functionalized 1 H-pyrrolo [3, 4-c] quinoline-1, 3 (2 H)-
diones (PQLs, 3) from N-phenylglycines and maleimides was developed. The cascade …

Delocalized quinolinium-macrocyclic peptides, an atypical chemotype for CNS penetration

V Pingitore, J Pancholi, TW Hornsby, J Warne… - Science …, 2024 - science.org
Macrocyclic drugs can address an increasing range of molecular targets but enabling
central nervous system (CNS) access to these drugs has been viewed as an intractable …

CDK8 inhibitors antagonize HIV-1 reactivation and promote provirus latency in T cells

RM Horvath, ZL Brumme, I Sadowski - Journal of Virology, 2023 - Am Soc Microbiol
Latent HIV-1 provirus represents the barrier toward a cure for infection and is dependent
upon the host RNA Polymerase (Pol) II machinery for reemergence. Here, we find that …