Targeting CDK2 in cancer: challenges and opportunities for therapy

S Tadesse, AT Anshabo, N Portman, E Lim, W Tilley… - Drug discovery today, 2020 - Elsevier
Highlights•CDK2 has key roles in cell cycle, DNA replication and DNA damage.•Multiple
biomarkers can indicate increased CDK2 activity.•Some cancers have particular …

Cyclin-dependent kinase 2 inhibitors in cancer therapy: an update

S Tadesse, EC Caldon, W Tilley… - Journal of medicinal …, 2018 - ACS Publications
Cyclin-dependent kinase 2 (CDK2) drives the progression of cells into the S-and M-phases
of the cell cycle. CDK2 activity is largely dispensable for normal development, but it is …

[HTML][HTML] 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 …

Cyclin E in normal physiology and disease states

C Chu, Y Geng, Y Zhou, P Sicinski - Trends in cell biology, 2021 - cell.com
E-type cyclins, collectively called cyclin E, represent key components of the core cell cycle
machinery. In mammalian cells, two E-type cyclins, E1 and E2, activate cyclin-dependent …

Development of isatin-thiazolo [3, 2-a] benzimidazole hybrids as novel CDK2 inhibitors with potent in vitro apoptotic anti-proliferative activity: Synthesis, biological and …

WM Eldehna, MA El Hassab, MF Abo-Ashour… - Bioorganic …, 2021 - Elsevier
In the current medical era, human health is experiencing numerous challenges, particularly
the human malignancies. Therefore, the therapeutic arsenal for these malignancies is to be …

[HTML][HTML] Cyclin-dependent kinase inhibitors and their therapeutic potential in colorectal cancer treatment

OM Thoma, MF Neurath, MJ Waldner - Frontiers in pharmacology, 2021 - frontiersin.org
Cyclin-dependent kinases (CDKs) are key players in cell cycle regulation. So far, more than
ten CDKs have been described. Their direct interaction with cyclins allow progression …

Novel oxindole/benzofuran hybrids as potential dual CDK2/GSK-3β inhibitors targeting breast cancer: design, synthesis, biological evaluation, and in silico studies

WM Eldehna, ST Al-Rashood, T Al-Warhi… - Journal of Enzyme …, 2021 - Taylor & Francis
The serine/threonine protein kinases CDK2 and GSK-3β are key oncotargets in breast
cancer cell lines, therefore, in the present study three series of oxindole-benzofuran hybrids …

Selective targeting of cyclin E1-amplified high-grade serous ovarian cancer by cyclin-dependent kinase 2 and AKT inhibition

G Au-Yeung, F Lang, WJ Azar, C Mitchell… - Clinical Cancer …, 2017 - AACR
Abstract Purpose: Cyclin E1 (CCNE1) amplification is associated with primary treatment
resistance and poor outcome in high-grade serous ovarian cancer (HGSC). Here, we …

[HTML][HTML] Spatial competition constrains resistance to targeted cancer therapy

K Bacevic, R Noble, A Soffar, O Wael Ammar… - Nature …, 2017 - nature.com
Adaptive therapy (AT) aims to control tumour burden by maintaining therapy-sensitive cells
to exploit their competition with resistant cells. This relies on the assumption that resistant …

Cyclin-dependent kinase (CDK) inhibitors: structure–activity relationships and insights into the CDK-2 selectivity of 6-substituted 2-arylaminopurines

CR Coxon, E Anscombe, SJ Harnor… - Journal of medicinal …, 2017 - ACS Publications
Purines and related heterocycles substituted at C-2 with 4′-sulfamoylanilino and at C-6
with a variety of groups have been synthesized with the aim of achieving selectivity of …