Cyclin dependent kinase 4 as promising drug target in adrenocortical carcinoma

2019 ◽  
Author(s):  
Raimunde Liang ◽  
Isabel Weigand ◽  
Silviu Sbiera ◽  
Stefan Kircher ◽  
Juliane Lippert ◽  
...  
Keyword(s):  
Adrenocortical Carcinoma ◽  
Drug Target ◽  
Cyclin Dependent Kinase

scholarly journals Perspective of Cyclin-dependent kinase 9 (CDK9) as a Drug Target

2012 ◽  
Vol 18 (20) ◽  
pp. 2883-2890 ◽  
Author(s):  
Vladimir Krystof ◽  
Sonja Baumli ◽  
Robert Furst
Keyword(s):  
Drug Target ◽  
Cyclin Dependent Kinase

scholarly journals CDK8-Novel Therapeutic Opportunities

2019 ◽  
Vol 12 (2) ◽  
pp. 92 ◽  
Author(s):  
Ingeborg Menzl ◽  
Agnieszka Witalisz-Siepracka ◽  
Veronika Sexl
Keyword(s):  
Prostate Cancer ◽  
Cancer Therapy ◽  
Drug Target ◽  
Potential Drug Target ◽  
Cyclin Dependent Kinase ◽  
Potential Drug ◽  
Biological Functions ◽  
Novel Treatment ◽  
Breast And Prostate Cancer ◽  
Novel Therapeutic

Improvements in cancer therapy frequently stem from the development of new small-molecule inhibitors, paralleled by the identification of biomarkers that can predict the treatment response. Recent evidence supports the idea that cyclin-dependent kinase 8 (CDK8) may represent a potential drug target for breast and prostate cancer, although no CDK8 inhibitors have entered the clinics. As the available inhibitors have been recently reviewed, we focus on the biological functions of CDK8 and provide an overview of the complexity of CDK8-dependent signaling throughout evolution and CDK8-dependent effects that may open novel treatment avenues.

scholarly journals Cyclin-dependent kinase 12 is a drug target for visceral leishmaniasis

Nature ◽  
2018 ◽  
Vol 560 (7717) ◽  
pp. 192-197 ◽  
Author(s):  
Susan Wyllie ◽  
Michael Thomas ◽  
Stephen Patterson ◽  
Sabrinia Crouch ◽  
Manu De Rycker ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Drug Target ◽  
Cyclin Dependent Kinase

p19INK4d: More than Just a Cyclin-Dependent Kinase Inhibitor

2019 ◽  
Vol 21 (1) ◽  
pp. 96-102
Author(s):  
Xu Han ◽  
Yijin Kuang ◽  
Huiyong Chen ◽  
Ting Liu ◽  
Ji Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Drug Target ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Cell Cycle Regulators ◽  
Cyclin Dependent Kinase ◽  
Disease Treatment ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Damage Repair

Cyclin-dependent kinase inhibitors (CDKIs) are important cell cycle regulators. The CDKI family is composed of the INK4 family and the CIP/KIP family. p19INK4d belongs to the INK4 gene family and is involved in a series of normal physiological activities and the pathogenesis of diseases. Many factors play regulatory roles in the p19INK4d gene expression at the transcriptional and posttranscriptional levels. p19INK4d not only regulates the cell cycle but also plays regulatory roles in apoptosis, DNA damage repair, cell differentiation of hematopoietic cells, and cellular senescence. In this review, the regulatory network of the p19INK4d gene expression and its biological functions are summarized, which provides a basis for further study of p19INK4d as a drug target for disease treatment.

scholarly journals Inhibitors of Leishmania mexicana CRK3 Cyclin-Dependent Kinase: Chemical Library Screen and Antileishmanial Activity

2004 ◽  
Vol 48 (8) ◽  
pp. 3033-3042 ◽  
Author(s):  
Karen M. Grant ◽  
Morag H. Dunion ◽  
Vanessa Yardley ◽  
Alexios-Leandros Skaltsounis ◽  
Doris Marko ◽  
...  
Keyword(s):  
Drug Target ◽  
Leishmania Donovani ◽  
Kinase Inhibitor ◽  
Genetic Manipulation ◽  
Protein Kinase Inhibitors ◽  
Antileishmanial Activity ◽  
Kinase Assay ◽  
Cyclin Dependent Kinase ◽  
Chemical Library

ABSTRACT The CRK3 cyclin-dependent kinase of Leishmania has been shown by genetic manipulation of the parasite to be essential for proliferation. We present data which demonstrate that chemical inhibition of CRK3 impairs the parasite's viability within macrophages, thus further validating CRK3 as a potential drug target. A microtiter plate-based histone H1 kinase assay was developed to screen CRK3 against a chemical library enriched for protein kinase inhibitors. Twenty-seven potent CRK3 inhibitors were discovered and screened against Leishmania donovani amastigotes in vitro. Sixteen of the CRK3 inhibitors displayed antileishmanial activity, with a 50% effective dose (ED50) of less than 10 μM. These compounds fell into four chemical classes: the 2,6,9-trisubstituted purines, including the C-2-alkynylated purines; the indirubins; the paullones; and derivatives of the nonspecific kinase inhibitor staurosporine. The paullones and staurosporine derivatives were toxic to macrophages. The 2,6,9-trisubstituted purines inhibited CRK3 in vitro, with 50% inhibitory concentrations ranging from high nanomolar to low micromolar concentrations. The most potent inhibitors of CRK3 (compounds 98/516 and 97/344) belonged to the indirubin class; the 50% inhibitory concentrations for these inhibitors were 16 and 47 nM, respectively, and the ED50s for these inhibitors were 5.8 and 7.6 μM, respectively. In culture, the indirubins caused growth arrest, a change in DNA content, and aberrant cell types, all consistent with the intracellular inhibition of a cyclin-dependent kinase and disruption of cell cycle control. Thus, use of chemical inhibitors supports genetic studies to confirm CRK3 as a validated drug target in Leishmania and provides pharmacophores for further drug development.

Memapsin 2, a drug target for Alzheimer's disease

2003 ◽  
Vol 70 ◽  
pp. 213-220 ◽  
Author(s):  
Gerald Koelsch ◽  
Robert T. Turner ◽  
Lin Hong ◽  
Arun K. Ghosh ◽  
Jordan Tang
Keyword(s):  
Crystal Structure ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transition State ◽  
Amyloid Precursor Protein ◽  
Therapeutic Target ◽  
Drug Target ◽  
Aspartic Protease ◽  
Precursor Protein ◽  
Memapsin 2

Mempasin 2, a ϐ-secretase, is the membrane-anchored aspartic protease that initiates the cleavage of amyloid precursor protein leading to the production of ϐ-amyloid and the onset of Alzheimer's disease. Thus memapsin 2 is a major therapeutic target for the development of inhibitor drugs for the disease. Many biochemical tools, such as the specificity and crystal structure, have been established and have led to the design of potent and relatively small transition-state inhibitors. Although developing a clinically viable mempasin 2 inhibitor remains challenging, progress to date renders hope that memapsin 2 inhibitors may ultimately be useful for therapeutic reduction of ϐ-amyloid.

520: Establishment of an Adrenocortical Carcinoma Cell Line (SO-RY), and its Characterization Including Adrenal Cortical Steroidogenesis

2005 ◽  
Vol 173 (4S) ◽  
pp. 141-142
Author(s):  
Yutaka Kamiyama ◽  
Hiroshi Okada ◽  
Koujiro Nishio ◽  
Takashi Yoshii ◽  
Keisuke Saito ◽  
...  
Keyword(s):  
Cell Line ◽  
Adrenocortical Carcinoma ◽  
Carcinoma Cell ◽  
Carcinoma Cell Line
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