scholarly journals Inhibition of Migration, Invasion and Drug Resistance of Pancreatic Adenocarcinoma Cells – Role of Snail, Slug and Twist and Small Molecule Inhibitors

2020 ◽  
Vol Volume 13 ◽  
pp. 5763-5777
Author(s):  
Ezgi Kaşıkcı ◽  
Esra Aydemir ◽  
Omer Faruk Bayrak ◽  
Fikrettin Sahin
Keyword(s):  
Drug Resistance ◽  
Pancreatic Adenocarcinoma ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Adenocarcinoma Cells

Small-molecule degraders of cyclin-dependent kinase protein: a review

2021 ◽  
Author(s):  
Bin Yu ◽  
Zekun Du ◽  
Yuming Zhang ◽  
Zhiyu Li ◽  
Jinlei Bian
Keyword(s):  
Cell Cycle ◽  
Drug Resistance ◽  
Protein Degradation ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Structural Characteristics ◽  
Protein A ◽  
Cyclin Dependent Kinase ◽  
Chemical Tools ◽  
Potential Therapeutics

Proteolysis-targeting chimeras are a new modality of chemical tools and potential therapeutics involving the induction of protein degradation. Cyclin-dependent kinase (CDK) protein, which is involved in cycles and transcription cycles, participates in regulation of the cell cycle, transcription and splicing. Proteolysis-targeting chimeras targeting CDKs show several advantages over traditional CDK small-molecule inhibitors in potency, selectivity and drug resistance. In addition, the discovery of molecule glues promotes the development of CDK degraders. Herein, the authors describe the existing CDK degraders and focus on the discussion of the structural characteristics and design of these degraders.

scholarly journals Role of Small Molecule Targeted Compounds in Cancer: Progress, Opportunities, and Challenges

2021 ◽  
Vol 9 ◽  
Author(s):  
Guoqiang Sun ◽  
Dawei Rong ◽  
Zhouxiao Li ◽  
Guangshun Sun ◽  
Fan Wu ◽  
...  
Keyword(s):  
Immune Response ◽  
Drug Resistance ◽  
Targeted Therapy ◽  
Drug Administration ◽  
Small Molecule ◽  
Molecular Targeted Therapy ◽  
Low Cost ◽  
Future Directions ◽  
Clinical Drug

Research on molecular targeted therapy of tumors is booming, and novel targeted therapy drugs are constantly emerging. Small molecule targeted compounds, novel targeted therapy drugs, can be administered orally as tablets among other methods, and do not draw upon genes, causing no immune response. It is easily structurally modified to make it more applicable to clinical needs, and convenient to promote due to low cost. It refers to a hotspot in the research of tumor molecular targeted therapy. In the present study, we review the current Food and Drug Administration (FDA)-approved use of small molecule targeted compounds in tumors, summarize the clinical drug resistance problems and mechanisms facing the use of small molecule targeted compounds, and predict the future directions of the evolving field.

scholarly journals Perspectives, past, present and future: the proline cycle/proline-collagen regulatory axis

Amino Acids ◽  
2021 ◽  
Author(s):  
James M. Phang
Keyword(s):  
Extracellular Matrix ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Human Tumors ◽  
Regulatory Link

AbstractIn the 35 years since the introduction of the “proline cycle”, its relevance to human tumors has been widely established. These connections are based on a variety of mechanisms discovered by many laboratories and have stimulated the search for small molecule inhibitors to treat cancer or metastases. In addition, the multi-layered connections of the proline cycle and the role of proline and hydroxyproline in collagen provide an important regulatory link between the extracellular matrix and metabolism.

scholarly journals Small-Molecule Inhibitors Targeting Proteasome-Associated Deubiquitinases

2021 ◽  
Vol 22 (12) ◽  
pp. 6213
Author(s):  
Seonghyeon Moon ◽  
Srinivasan Muniyappan ◽  
Sung-Bae Lee ◽  
Byung-Hoon Lee
Keyword(s):  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Kinetic Studies ◽  
26S Proteasome ◽  
Chemical Screening ◽  
Cellular Context ◽  
Substrate Processing ◽  
Intracellular Proteolysis ◽  
Processing Steps

The 26S proteasome is the principal protease for regulated intracellular proteolysis. This multi-subunit complex is also pivotal for clearance of harmful proteins that are produced throughout the lifetime of eukaryotes. Recent structural and kinetic studies have revealed a multitude of conformational states of the proteasome in substrate-free and substrate-engaged forms. These conformational transitions demonstrate that proteasome is a highly dynamic machinery during substrate processing that can be also controlled by a number of proteasome-associated factors. Essentially, three distinct family of deubiquitinases–USP14, RPN11, and UCH37–are associated with the 19S regulatory particle of human proteasome. USP14 and UCH37 are capable of editing ubiquitin conjugates during the process of their dynamic engagement into the proteasome prior to the catalytic commitment. In contrast, RPN11-mediated deubiquitination is directly coupled to substrate degradation by sensing the proteasome’s conformational switch into the commitment steps. Therefore, proteasome-bound deubiquitinases are likely to tailor the degradation events in accordance with substrate processing steps and for dynamic proteolysis outcomes. Recent chemical screening efforts have yielded highly selective small-molecule inhibitors for targeting proteasomal deubiquitinases, such as USP14 and RPN11. USP14 inhibitors, IU1 and its progeny, were found to promote the degradation of a subset of substrates probably by overriding USP14-imposed checkpoint on the proteasome. On the other hand, capzimin, a RPN11 inhibitor, stabilized the proteasome substrates and showed the anti-proliferative effects on cancer cells. It is highly conceivable that these specific inhibitors will aid to dissect the role of each deubiquitinase on the proteasome. Moreover, customized targeting of proteasome-associated deubiquitinases may also provide versatile therapeutic strategies for induced or repressed protein degradation depending on proteolytic demand and cellular context.

scholarly journals Small molecule inhibitors reveal an indispensable scaffolding role of RIPK 2 in NOD 2 signaling

2018 ◽  
Vol 37 (17) ◽  
Author(s):  
Matous Hrdinka ◽  
Lisa Schlicher ◽  
Bing Dai ◽  
Daniel M Pinkas ◽  
Joshua C Bufton ◽  
...  
Keyword(s):  
Small Molecule ◽  
Small Molecule Inhibitors
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