Top 4 Biorxiv Papers Today in Pharmacology And Toxicology


1.997 Mikeys
#1. Development of the first low nanomolar Liver Receptor Homolog-1 agonist through structure-guided design
Suzanne G Mays, Autumn R Flynn, Jeffrey L Corneilson, C. Denise Okafor, Hongtao Wang, Guohui Wang, Xiangsheng Huang, Heather N Donaldson, Elizabeth J Millings, Rohini Polavarapu, David Moore, John Calvert, Nathan Jui, Eric Anthony Ortlund
As a key regulator of metabolism and inflammation, the orphan nuclear hormone receptor, Liver Receptor Homolog-1 (LRH-1), has potential as a therapeutic target for diabetes, nonalcoholic fatty live disease, and inflammatory bowel diseases. Discovery of LRH-1 modulators has been difficult, in part due to the tendency for synthetic compounds to bind unpredictably within the lipophilic binding pocket. Using a structure-guided approach, we exploited a newly-discovered polar interaction to lock agonists in a consistent orientation. This enabled the discovery of the first low nanomolar LRH-1 agonist, one hundred times more potent than the best previous modulator. We elucidate a novel mechanism of action that relies upon specific polar interactions deep in the LRH-1 binding pocket. In an organoid model of inflammatory bowel disease, the new agonist increases expression ofLRH-1-conrolled steroidogenic genes and promotes anti-inflammatory gene expression changes. These studies constitute major progress in developing LRH-1 modulators with...
more | pdf
Figures
Tweets
Github
None.
Youtube
None.
Other stats
Sample Sizes : None.
Authors: 14
Total Words: 13616
Unqiue Words: 4212

1.997 Mikeys
#2. Assessment of chemotherapy-induced organ damage with 68Ga-labeled duramycin
Anne Rix, Natascha Ingrid Drude, Anna Mrugalla, Ferhan Baskaya, Koon Yan Pak, Brian Gray, Hans-Juergen Kaiser, Rene Hany Tolba, Eva Fiegle, Wiltrud Lederle, Felix Manuel Mottaghy, Fabian Kiessling
Compared to standard toxicological techniques in preclinical toxicity studies, non−invasive imaging of organ toxicity enables fast and longitudinal investigation of the whole animal. Therefore, we set out to evaluate [68Ga]Ga−NODAGA−duramycin as a positron emission tomography (PET)−tracer of cell death for detecting chemotherapy−induced organ toxicity. Methods: NODAGA−duramycin was radiolabeled with 68Ga, and quality control was done by thin layer chromatography and high performance liquid chromatography. Tracer specificity was determined in vitro by performing competitive binding experiments on ethanol treated cells. To optimize the timing of the PET/CT−based tracer evaluation, kinetic studies were performed in untreated and cisplatin−treated (20 mg/kg BW, intraperitoneal (i.p.)) BALB/cAnNRj mice. Organ uptake was analyzed in doxorubicin (4 mg/kg BW, i.p.)−, busulfan (18.8 mg/kg KG, i.p.)−, and cisplatin−treated (20 mg/kg BW, i.p.) mice, and in untreated control mice 2 hours after intravenous injection of 5−10 MBq...
more | pdf
Figures
Tweets
biorxivpreprint: Assessment of chemotherapy-induced organ damage with 68Ga-labeled duramycin https://t.co/eo3RCHdkkb #bioRxiv
sbotlite: RT @biorxivpreprint: Assessment of chemotherapy-induced organ damage with 68Ga-labeled duramycin https://t.co/eo3RCHdkkb #bioRxiv
Github
None.
Youtube
None.
Other stats
Sample Sizes : None.
Authors: 12
Total Words: 7271
Unqiue Words: 2393

1.997 Mikeys
#3. Variability in Human Drug Metabolizing Cytochrome P450 CYP2C9, CYP2C19 and CYP3A5 Activities Caused by Genetic Variations in Cytochrome P450 Oxidoreductase
Maria Natalia Rojas Velazques, Shaheena Parween, Sameer S Udhane, Amit V Pandey
A broad spectrum of human diseases are caused by mutations in the NADPH cytochrome P450 oxidoreductase (POR). Cytochrome P450 proteins perform several reactions, including the metabolism of steroids, drugs, and other xenobiotics. In 2004 the first human patients with defects in POR were reported, and over 250 variations in POR are known. Information about the effects of POR variants on drug metabolizing enzymes is limited and has not received much attention. By analyzing the POR sequences from genomics databases, we identified potentially disease-causing variations and characterized these by in vitro functional studies using recombinant proteins. Proteins were expressed in bacteria and purified for activity assays. Activities of cytochrome P450 enzymes were tested in vitro using liposomes prepared with lipids into which P450 and P450 reductase proteins were embedded. Here we are reporting the effect of POR variants on drug metabolizing enzymes CYP2C9, CYP2C19, and CYP3A5 which are responsible for the metabolism of many drugs. POR...
more | pdf
Figures
Tweets
biorxivpreprint: Variability in Human Drug Metabolizing Cytochrome P450 CYP2C9, CYP2C19 and CYP3A5 Activities Caused by Genetic Variations in Cytochrome P450 Oxidoreductase https://t.co/EUN4F2dYQi #bioRxiv
Github
None.
Youtube
None.
Other stats
Sample Sizes : None.
Authors: 4
Total Words: 5003
Unqiue Words: 1593

1.997 Mikeys
#4. Acute Thiamethoxam exposure in Apis mellifera : Absence of both stress-induced changes in mRNA splicing and synergistic effects of common fungicide and herbicide
Pamela Decio, Pinar Ustaoglu, Thaisa C Roat, Osmar Malaspina, Jean-Marc Devaud, Reinhard Stoger, Matthias Soller
Securing food supply for a growing population is one of the current major challenges and heavily relies on the use of agrochemicals to maximize crop yield. Neonicotinoids are globally one of the most widely used insecticides. It is increasingly recognized, that neonicotinoids have a negative impact on non-target organisms, including important pollinators such as the European honey bee Apis mellifera. Toxicity of neonicotinoids may be enhanced through simultaneous exposure with additional pesticides, which could help explain, in part, the global decline of honey bee colonies. Here we examined whether exposure effects of the neonicotinoid Thiamethoxam are enhanced by the commonly used fungicide Carbendazim and the herbicide Glyphosate. For the first time, we also analysed alternative splicing changes upon pesticide exposure in the honey bee. In particular, we examined transcripts of three genes: i) the stress sensor gene X box binding protein-1 (Xbp1), ii) the Down Syndrome Cell Adhesion Molecule (Dscam) gene and iii) the embryonic...
more | pdf
Figures
Tweets
biorxivpreprint: Acute Thiamethoxam exposure in Apis mellifera : Absence of both stress-induced changes in mRNA splicing and synergistic effects of common fungicide and herbicide https://t.co/OztS7JFXNu #bioRxiv
Github
None.
Youtube
None.
Other stats
Sample Sizes : None.
Authors: 7
Total Words: 7243
Unqiue Words: 2379

About

Assert is a website where the best academic papers on arXiv (computer science, math, physics), bioRxiv (biology), BITSS (reproducibility), EarthArXiv (earth science), engrXiv (engineering), LawArXiv (law), PsyArXiv (psychology), SocArXiv (social science), and SportRxiv (sport research) bubble to the top each day.

Papers are scored (in real-time) based on how verifiable they are (as determined by their Github repos) and how interesting they are (based on Twitter).

To see top papers, follow us on twitter @assertpub_ (arXiv), @assert_pub (bioRxiv), and @assertpub_dev (everything else).

To see beautiful figures extracted from papers, follow us on Instagram.

Tracking 128,326 papers.

Search
Sort results based on if they are interesting or reproducible.
Interesting
Reproducible
Feedback
Online
Stats
Tracking 128,326 papers.