scholarly journals Model‐informed drug repurposing: Viral kinetic modelling to prioritize rational drug combinations for COVID‐19

2020 ◽  
Author(s):  
Michael G. Dodds ◽  
Rajesh Krishna ◽  
Antonio Goncalves ◽  
Craig R. Rayner
Keyword(s):  
Kinetic Modelling ◽  
Drug Repurposing ◽  
Drug Combinations ◽  
Viral Kinetic ◽  
Rational Drug

Kinetic modelling of NSAID action on COX-1: Focus on in vitro/in vivo aspects and drug combinations

2009 ◽  
Vol 36 (1) ◽  
pp. 122-136 ◽  
Author(s):  
Alexey Goltsov ◽  
Anton Maryashkin ◽  
Maciej Swat ◽  
Yuri Kosinsky ◽  
Ian Humphery-Smith ◽  
...  
Keyword(s):  
Kinetic Modelling ◽  
Drug Combinations ◽  
Cox 1

Abstract PR9: Investigating combinatorial ligand addiction provides insights into rational drug combinations in cancer therapy

2012 ◽  
Author(s):  
Emily A. Pace ◽  
Ulrik B. Nielsen ◽  
Birgit Schoeberl ◽  
Diana H. Chai ◽  
Anand Parikh ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Drug Combinations ◽  
Rational Drug

scholarly journals Development of Rational Drug Combinations with Investigational Targeted Agents

2010 ◽  
Vol 15 (5) ◽  
pp. 496-499 ◽  
Author(s):  
Adam Clark ◽  
Matthew Ellis ◽  
Charles Erlichman ◽  
Stuart Lutzker ◽  
James Zwiebel
Keyword(s):  
Drug Combinations ◽  
Targeted Agents ◽  
Rational Drug

scholarly journals NICEdrug.ch, a workflow for rational drug design and systems-level analysis of drug metabolism

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Homa MohammadiPeyhani ◽  
Anush Chiappino-Pepe ◽  
Kiandokht Haddadi ◽  
Jasmin Hafner ◽  
Noushin Hadadi ◽  
...  
Keyword(s):  
Drug Targets ◽  
Drug Repurposing ◽  
Rational Drug Design ◽  
Bioactive Molecules ◽  
Lead Discovery ◽  
Minimal Impact ◽  
Practical Applications ◽  
Rational Drug ◽  
Golden Standard ◽  
And Performance

The discovery of a drug requires over a decade of intensive research and financial investments – and still has a high risk of failure. To reduce this burden, we developed the NICEdrug.ch resource, which incorporates 250,000 bioactive molecules, and studied their enzymatic metabolic targets, fate, and toxicity. NICEdrug.ch includes a unique fingerprint that identifies reactive similarities between drug–drug and drug–metabolite pairs. We validated the application, scope, and performance of NICEdrug.ch over similar methods in the field on golden standard datasets describing drugs and metabolites sharing reactivity, drug toxicities, and drug targets. We use NICEdrug.ch to evaluate inhibition and toxicity by the anticancer drug 5-fluorouracil, and suggest avenues to alleviate its side effects. We propose shikimate 3-phosphate for targeting liver-stage malaria with minimal impact on the human host cell. Finally, NICEdrug.ch suggests over 1300 candidate drugs and food molecules to target COVID-19 and explains their inhibitory mechanism for further experimental screening. The NICEdrug.ch database is accessible online to systematically identify the reactivity of small molecules and druggable enzymes with practical applications in lead discovery and drug repurposing.

scholarly journals Fi-score: a novel approach to characterise protein topology and aid in drug discovery studies

2020 ◽  
Author(s):  
Austė Kanapeckaitė ◽  
Claudia Beaurivage ◽  
Matthew Hancock ◽  
Erik Verschueren
Keyword(s):  
Dihedral Angle ◽  
Target Selection ◽  
Gaussian Mixture Models ◽  
Drug Repurposing ◽  
Gaussian Mixture ◽  
Rational Drug Design ◽  
Drug Candidates ◽  
Novel Approach ◽  
Protein Fingerprinting ◽  
Rational Drug

AbstractTarget evaluation is at the centre of rational drug design and biologics development. In order to successfully engineer antibodies, T-cell receptors or small molecules it is necessary to identify and characterise potential binding or contact sites on therapeutically relevant target proteins. Currently, there are numerous challenges in achieving a better docking precision as well as characterising relevant sites. We devised a first-of-its-kind in silico protein fingerprinting approach based on dihedral angle and B-factor distribution to probe binding sites and sites of structural importance. In addition, we showed that the entire protein regions or individual structural subsets can be profiled using our derived fi-score based on amino acid dihedral angle and B-factor distribution. We further described a method to assess the structural profile and extract information on sites of importance using machine learning Gaussian mixture models. In combination, these biophysical analytical methods could potentially help to classify and systematically analyse not only targets but also drug candidates that bind to specific sites which would greatly improve pre-screening stage, target selection and drug repurposing efforts in finding other matching targets.

scholarly journals Identification of Antifungal Compounds against Multidrug Resistant Candida auris Utilizing a High Throughput Drug Repurposing Screen

2021 ◽  
Author(s):  
Yu-Shan Cheng ◽  
Jose Santinni Roma ◽  
Min Shen ◽  
Caroline Mota Fernandes ◽  
Patricia S. Tsang ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Treatment Options ◽  
Drug Repurposing ◽  
Multidrug Resistant ◽  
Current Treatment ◽  
Drug Combinations ◽  
Serine Palmitoyltransferase ◽  
Candida Auris ◽  
Pharmacologically Active

Candida auris is an emerging fatal fungal infection that has resulted in several outbreaks in hospitals and care facilities. Current treatment options are limited by the development of drug resistance. Identifying new pharmaceuticals to combat these drug-resistant infections will thus be required to overcome this unmet medical need. We have established a bioluminescent ATP-based assay to identify new compounds and potential drug combinations showing effective growth inhibition against multiple strains of multidrug resistant Candida auris. The assay is robust and suitable for assessing large compound collections by high throughput screening. Utilizing this assay, we conducted a screen of 4,314 approved drugs and pharmacologically active compounds which yielded 25 compounds including 6 novel anti-Candida auris compounds and 13 sets of potential two drug combinations. Among the drug combinations, the serine palmitoyltransferase inhibitor myriocin demonstrated a combinational effect with flucytosine against all tested isolates during screening. This combinational effect was confirmed in 13 clinical isolates of Candida auris.

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