scholarly journals Nuclear receptors: recent drug discovery for cancer therapies

2019 ◽  
Author(s):  
Linjie Zhao ◽  
Shengtao Zhou ◽  
Jan-Åke Gustafsson
Keyword(s):  
Drug Discovery ◽  
Nuclear Receptors ◽  
Cancer Therapies

scholarly journals ONRLDB—manually curated database of experimentally validated ligands for orphan nuclear receptors: insights into new drug discovery

Database ◽  
2015 ◽  
Vol 2015 ◽  
pp. bav112 ◽  
Author(s):  
Ravikanth Nanduri ◽  
Isha Bhutani ◽  
Arun Kumar Somavarapu ◽  
Sahil Mahajan ◽  
Raman Parkesh ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Nuclear Receptors ◽  
Orphan Nuclear Receptors ◽  
New Drug

A Molecular Guidance System Based Upon Target Genes, Nuclear Receptors and Ligands Applied to Drug Discovery and Prediction of Toxicity

2008 ◽  
Vol 8 (12) ◽  
pp. 1252-1264 ◽  
Author(s):  
Virendra Mahesh ◽  
Neil Sidell ◽  
Douglas Ewing ◽  
Edwin Bransome Jr. ◽  
Lawrence Hendry
Keyword(s):  
Drug Discovery ◽  
Nuclear Receptors ◽  
Target Genes ◽  
Guidance System ◽  
Molecular Guidance

scholarly journals Early Drug Discovery and Development of Novel Cancer Therapeutics Targeting DNA Polymerase Eta (POLH)

2021 ◽  
Vol 11 ◽  
Author(s):  
David M. Wilson ◽  
Matthew A. J. Duncton ◽  
Caleb Chang ◽  
Christine Lee Luo ◽  
Taxiarchis M. Georgiadis ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Dna Polymerase ◽  
Synthetic Lethality ◽  
Cancer Therapeutics ◽  
Nucleoside Analogs ◽  
Standard Of Care ◽  
Rapid Identification ◽  
Cancer Therapies ◽  
Polymerase Eta

Polymerase eta (or Pol η or POLH) is a specialized DNA polymerase that is able to bypass certain blocking lesions, such as those generated by ultraviolet radiation (UVR) or cisplatin, and is deployed to replication foci for translesion synthesis as part of the DNA damage response (DDR). Inherited defects in the gene encoding POLH (a.k.a., XPV) are associated with the rare, sun-sensitive, cancer-prone disorder, xeroderma pigmentosum, owing to the enzyme’s ability to accurately bypass UVR-induced thymine dimers. In standard-of-care cancer therapies involving platinum-based clinical agents, e.g., cisplatin or oxaliplatin, POLH can bypass platinum-DNA adducts, negating benefits of the treatment and enabling drug resistance. POLH inhibition can sensitize cells to platinum-based chemotherapies, and the polymerase has also been implicated in resistance to nucleoside analogs, such as gemcitabine. POLH overexpression has been linked to the development of chemoresistance in several cancers, including lung, ovarian, and bladder. Co-inhibition of POLH and the ATR serine/threonine kinase, another DDR protein, causes synthetic lethality in a range of cancers, reinforcing that POLH is an emerging target for the development of novel oncology therapeutics. Using a fragment-based drug discovery approach in combination with an optimized crystallization screen, we have solved the first X-ray crystal structures of small novel drug-like compounds, i.e., fragments, bound to POLH, as starting points for the design of POLH inhibitors. The intrinsic molecular resolution afforded by the method can be quickly exploited in fragment growth and elaboration as well as analog scoping and scaffold hopping using medicinal and computational chemistry to advance hits to lead. An initial small round of medicinal chemistry has resulted in inhibitors with a range of functional activity in an in vitro biochemical assay, leading to the rapid identification of an inhibitor to advance to subsequent rounds of chemistry to generate a lead compound. Importantly, our chemical matter is different from the traditional nucleoside analog-based approaches for targeting DNA polymerases.

scholarly journals Advancing Computer-Aided Drug Discovery (ACADD): In-Silico Approach towards Nuclear Receptors by Big Data

2021 ◽  
pp. 40-46
Author(s):  
K. Palaniammal ◽  
M. Saravana Roentgen Mani ◽  
R. Mohan Kumar
Keyword(s):  
Big Data ◽  
Biological Activity ◽  
Drug Discovery ◽  
Binding Energy ◽  
Nuclear Receptors ◽  
In Silico ◽  
Structural Parameters ◽  
Receptor Interaction ◽  
Drug Discovery And Development ◽  
Computer Aided

The progression of drug discovery and development is time consuming and costly. Advancing Computer-aided drug discovery (ACADD) is an effective tool in reducing the time and cost of research and development. This study deals with the evaluation of the nuclear receptors for the in-silico biological activity using ligand betulinic acid and dexamethasone. Docking results showed that binding energy was -74.190 kcal/mol when compared with that of the standard (-51.551 kcal/mol). Interaction energy -44.16 & -25.14 kcal/mol) of the ligands also coincide with the binding energy. These ligands have shown the best ligand-receptor interaction based on their structural parameters.

scholarly journals ROR nuclear receptors: structures, related diseases, and drug discovery

2014 ◽  
Vol 36 (1) ◽  
pp. 71-87 ◽  
Author(s):  
Yan Zhang ◽  
Xiao-yu Luo ◽  
Dong-hai Wu ◽  
Yong Xu
Keyword(s):  
Drug Discovery ◽  
Nuclear Receptors
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