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nih.gov
https://pmc.ncbi.nlm.nih.gov › articles
Global Phosphoproteomics reveal CDK suppression as a …
CRISPR/Cas9 viability database analysis revealed that, in mt KRas-driven pancreatic cancer cells, knocking out the cell cycle regulators CDK1 or CDK2 or the transcriptional regulators …
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Fierce Biotech
https://www.fiercebiotech.com › research
ESMO: Syros targets KRAS-mutant cancer as CDK7 …
Sep 20, 2021 · By inhibiting CDK7, SY-5609 has shown potential to treat cancer by reining in uncontrolled cell proliferation and suppressing the expression of …
Author: Angus Liu
Wiley Online Library
https://onlinelibrary.wiley.com › doi › full
The suppressive efficacy of THZ1 depends on KRAS …
Nov 30, 2023 · Inhibition of CDK7, a potent transcription regulator, may bring new hope for treating pancreatic ductal adenocarcinoma (PDAC), which is featured by large genetic heterogeneity and abundant KRAS mutations.
Studies of Kras CDK7
PubMed
Global Phosphoproteomics Reveal CDK Suppression as a Vulnerability to KRas Addiction in Pancreatic Cancer
Purpose: Among human cancers that harbor mutant (mt) KRas, some, but not all, are dependent on mt KRas. However, little is known about what drives KRas dependency. Experimental design: Global phosphoproteomics, screening of a chemical library of FDA drugs, and genome-wide CRISPR/Cas9 viability d...
Author: Aslamuzzama…
Published: 2021/07/15
Keywords: Among hu…
ScienceDirect
Perspective Cyclin-dependent kinase 7 inhibitor THZ1 in cancer therapy
Current cancer therapies have encountered adverse response due to poor therapeutic efficiency, severe side effects and acquired resistance to multiple drugs. Thus, there are urgent needs for finding new cancer-targeted pharmacological strategies. In this review, we summarized the current understandi...
Published: 2019/09/01
Cited By: 0
Keywords: THZ1; Cycl…
National Center for Biotechnology Information
The covalent CDK7 inhibitor THZ1 potently induces apoptosis in multiple myeloma cells in vitro and in vivo
Cyclin-dependent kinases (CDKs) catalyze the phosphorylation of cyclins, proteins intimately involved in the progression of cells through the cell cycle. However, in addition to their cell cycle regulatory activities, CDKs exert several functions unrelated to cell cycle control. For example, CDK9 ac...
Author: Yu Zhang, Lia…
Published: 2019/10/10
DOI: 10.1158/1078-043…
Massey Cancer Center
https://www.masseycancercenter.org › news › ...
Vulnerability in mutant KRAS pancreatic tumors discovered and …
Jun 16, 2021 · They found that CDK1 and CDK2 as well as CDK7 and CDK9 proteins were associated with mutant KRAS-addicted tumors. Lastly, they evaluated the ability of a library of …
ASCO Publications
https://ascopubs.org › doi
Trial in progress: Phase I study of SY-5609, a potent, selective …
Jun 2, 2022 · Preclinical studies have shown that CDK7 inhibition via SY-5609 inhibits tumor growth in KRAS mutant PDAC xenograft models, in many cases leading to regressions. SY …
nih.gov
https://pmc.ncbi.nlm.nih.gov › articles
Control of Expression of Key Cell Cycle Enzymes Drives Cell Line ...
Here, we employed a previously developed, highly specific small molecule inhibitor that non-covalently blocks ATP binding to CDK7 (LDC4297) to study the mechanisms underlying cell …
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Are KRAS mutations common in PDAC xenografts?
Oncogenic KRAS mutations are prevalent in PDAC. Mutant KRAS is a potent stimulator of mitogenic MAPK signaling and downstream transcriptional programs for cell proliferation. Preclinical studies have shown that CDK7 inhibition via SY-5609 inhibits tumor growth in KRAS mutant PDAC xenograft models, in many cases leading to regressions.
Trial in progress: Phase I study of SY-5609, a potent, selective CDK7
ascopubs.org
Does THZ1 a small-molecule covalent CDK7 inhibitor affect pdacs with different KRAS mutations?
This investigation aimed at exploring the discrepant efficacies of THZ1, a small-molecule covalent CDK7 inhibitor, on PDACs with different KRAS mutations and the underlying mechanisms. Associations of CDK7 expression with survival by KRAS mutations were first assessed.
The suppressive efficacy of THZ1 depends on - Wiley Online Library
onlinelibrary.wiley.com
Does high CDK7 expression affect apoptosis in kras-g12v PDAC patients?
High CDK7 expression was significantly linked to worse survival within PDAC patients carrying KRAS-G12V mutation but not in those with KRAS-G12D mutation. The apoptosis-inducing effect of THZ1 was markedly stronger in KRAS-G12V PDAC than KRAS-G12D cancer.
The suppressive efficacy of THZ1 depends on - Wiley Online Library
onlinelibrary.wiley.com
Is CDK7 inhibition a mechanism of THZ1 susceptibility in PDAC cells?
Finally, PDAC cell lines with primary or acquired resistance to THZ1 were investigated to explore the potential mechanism of THZ1 susceptibility. CDK7 inhibition was identified as a selective and potent therapeutic strategy for PDAC progression in multiple preclinical models.
THZ1 reveals CDK7-dependent transcriptional addictions in ... - Nature
nature.com
Is Cdk7 a potent target for pancreatic cancer?
CDK7 is identified as a potent target for pancreatic cancer. a Schematic overview of screening of epigenetic modulators in BxPC-3 and MiaPaCa-2 (left panel). All compounds were added to cells at the concentration of 0.1 and 1 μM, and cell viability was measured at 72 h. Compounds were then ranked based on their inhibitory effect.
THZ1 reveals CDK7-dependent transcriptional addictions in ... - Nature
nature.com
Is CDK7 downregulated in PDAC cells?
Downregulation of CDK7 in PDAC cells led to a significant decrease in cell growth (clone formation and proliferation), as illustrated by two THZ1-sensitive cell lines (MiaPaCa-2 and PDC0034) and one THZ1-insensitive cell line (SW1990) (Fig. 2d, e).
THZ1 reveals CDK7-dependent transcriptional addictions in ... - Nature
nature.com
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Annals of Oncology
https://www.annalsofoncology.org › article › fulltext
13P SY-5609, a highly potent and selective oral CDK7 inhibitor ...
SY-5609 is a CDK7 inhibitor in development in patients with solid tumors including pancreatic and lung cancers (NCT04247126). Here we report on SY-5609 preclinical activity in models of …
ascopubs.org
https://ascopubs.org › doi › pdf
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Trial in progress: Phase I study of SY-5609, a potent, selective …
Preclinical studies have shown that CDK7 inhibition via SY-5609 inhibits tumor growth in KRAS mutant PDAC xenograft models, in many cases leading to regressions. SY-5609 also …
PubMed
https://pubmed.ncbi.nlm.nih.gov
Global Phosphoproteomics Reveal CDK Suppression as a
Jul 15, 2021 · CRISPR/Cas9 viability database analysis revealed that, in mt KRas-driven pancreatic cancer cells, knocking out the cell-cycle regulators CDK1 or CDK2 or the …
American Association for Cancer Research
https://aacrjournals.org › clincancerres › article › ...
Global Phosphoproteomics Reveal CDK Suppression as …
Jul 15, 2021 · CRISPR/Cas9 viability database analysis revealed that, in mt KRas-driven pancreatic cancer cells, knocking out the cell-cycle regulators CDK1 or CDK2 or the transcriptional regulators CDK7 or CDK9 was as effective as …
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Global Phosphoproteomics reveal CDK suppression as a …

ESMO: Syros targets KRAS-mutant cancer as CDK7 …

The suppressive efficacy of THZ1 depends on KRAS …

Vulnerability in mutant KRAS pancreatic tumors discovered and …

Trial in progress: Phase I study of SY-5609, a potent, selective …

Control of Expression of Key Cell Cycle Enzymes Drives Cell Line ...

Trial in progress: Phase I study of SY-5609, a potent, selective CDK7

The suppressive efficacy of THZ1 depends on - Wiley Online Library

The suppressive efficacy of THZ1 depends on - Wiley Online Library

THZ1 reveals CDK7-dependent transcriptional addictions in ... - Nature

THZ1 reveals CDK7-dependent transcriptional addictions in ... - Nature

THZ1 reveals CDK7-dependent transcriptional addictions in ... - Nature

13P SY-5609, a highly potent and selective oral CDK7 inhibitor ...

Trial in progress: Phase I study of SY-5609, a potent, selective …

Global Phosphoproteomics Reveal CDK Suppression as a

Global Phosphoproteomics Reveal CDK Suppression as …