scholarly journals Pharmacodynamic assays to facilitate preclinical and clinical development of pre‐ mRNA splicing modulatory drug candidates

2015 ◽  
Vol 3 (4) ◽  
Author(s):  
Yihui Shi ◽  
Amanda S. Joyner ◽  
William Shadrick ◽  
Gustavo Palacios ◽  
Chandraiah Lagisetti ◽  
...  
Keyword(s):  
Clinical Development ◽  
Mrna Splicing ◽  
Drug Candidates

The Position of ADME Predictions in Multi-Objective QSAR

2021 ◽  
Vol 6 (1) ◽  
pp. 1-8
Author(s):  
Anna Tsantili-Kakoulidou
Keyword(s):  
Drug Efficacy ◽  
Clinical Development ◽  
Efficacy And Safety ◽  
Huge Amount ◽  
Multi Objective ◽  
Drug Candidates ◽  
Drug Molecules ◽  
Qsar Models ◽  
Adme Properties ◽  
Single Objective

ADME properties and toxicity predictions play an essential role in prioritization and optimization of drug molecules. According to recent statistics, drug efficacy and safety are principal reasons for drug failure. In this perspective, the position of ADME predictions in the evolution of traditional QSAR from the single objective of biological activity to a multi-task concept is discussed. The essential features of ADME and toxicity QSAR models are highlighted. Since such models are applied to prioritize existing or virtual project compounds with already established or predicted target affinity, a mechanistic interpretation, although desirable, is not a primary goal. However, a broad applicability domain is crucial. A future challenge with multi-objective QSAR is to adapt to the realm of big data by integrating techniques for the exploitation of the continuously increasing number of ADME data and the huge amount of clinical development endpoints for the sake of efficacy and safety of new drug candidates.

scholarly journals Repurposing the estrogen receptor modulator raloxifene to treat SARS-CoV-2 infection

2021 ◽  
Author(s):  
Marcello Allegretti ◽  
Maria Candida Cesta ◽  
Mara Zippoli ◽  
Andrea Beccari ◽  
Carmine Talarico ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Estrogen Receptor ◽  
Early Stage ◽  
Clinical Development ◽  
Immune Memory ◽  
Therapeutic Drug ◽  
The Novel ◽  
Drug Candidates ◽  
Receptor Modulator ◽  
Attractive Candidate

AbstractThe ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates strategies to identify prophylactic and therapeutic drug candidates to enter rapid clinical development. This is particularly true, given the uncertainty about the endurance of the immune memory induced by both previous infections or vaccines, and given the fact that the eradication of SARS-CoV-2 might be challenging to reach, given the attack rate of the virus, which would require unusually high protection by a vaccine. Here, we show how raloxifene, a selective estrogen receptor modulator with anti-inflammatory and antiviral properties, emerges as an attractive candidate entering clinical trials to test its efficacy in early-stage treatment COVID-19 patients.

scholarly journals Recent updates in the discovery and development of novel antimalarial drug candidates

MedChemComm ◽  
2018 ◽  
Vol 9 (3) ◽  
pp. 437-453 ◽  
Author(s):  
John Okombo ◽  
Kelly Chibale
Keyword(s):  
Antimalarial Drug ◽  
Antimalarial Drugs ◽  
Clinical Development ◽  
Radical Cure ◽  
Single Exposure ◽  
Drug Candidates

Concerns of emerging resistance and the search for molecules with potential for single exposure radical cure and prophylaxis have spurred research into compounds with target profiles for clinical development into antimalarial drugs.

Miniaturized screening technologies for drug discovery

2002 ◽  
Vol 30 (4) ◽  
pp. 802-806 ◽  
Author(s):  
J. M. Cooper ◽  
A. E. G. Cass
Keyword(s):  
Drug Discovery ◽  
Molecular Biology ◽  
Pharmaceutical Research ◽  
Toxicity Assessment ◽  
Clinical Development ◽  
Biological Screening ◽  
Drug Candidates ◽  
The Us ◽  
Pharmaceutical Research And Development ◽  
Microsystems Technology

Adaptive Profiling (APL) and other biochip companies aim to harness the power of microsystems technology together with advances in chemistry and molecular biology, to become service and technology providers to organizations involved in pharmaceutical research and development. By supplying a unique range of decisionmaking tools that aid an earlier identification of qualified drug candidates for clinical development, the company should gain a significant share of the US$10 billion biological screening, bioavailability and toxicity assessment market.

Natural Products in the Fight Against Multi-Drug-Resistant Bacteria

2021 ◽  
pp. 130-159
Author(s):  
Mümtaz Güran
Keyword(s):  
Natural Products ◽  
Treatment Options ◽  
Current Treatment ◽  
Clinical Development ◽  
Resistant Bacteria ◽  
Ongoing Research ◽  
Synthetic Compounds ◽  
Regulatory Issues ◽  
Drug Candidates ◽  
Drug Resistant Bacteria

It is well recognised that the antimicrobial resistance crisis has approached critical levels, and current treatment options are very limited, especially in the treatment of infections caused by resistant bacteria. Thus, ongoing research is focused on the development of new molecules which have broader antimicrobial activity. However, the advancements in drug development studies using synthetic compounds has led to a lack of success. Also, economic and regulatory issues have formed a challenge as well. Therefore, research has focused again on natural products. A large number of natural products and natural product-derived compounds are still in various stages of clinical development. Here, current research on the potential uses of natural products or their templates as viable sources of new drug candidates have been discussed to construct an understanding towards the goal of development of new antimicrobials to overcome resistant pathogens.

scholarly journals Characterization of raloxifene as potential pharmacological agent against SARS-CoV-2 and its variants

2021 ◽  
Author(s):  
Daniela Iaconis ◽  
Carmine Talarico ◽  
Candida Manelfi ◽  
Maria Candida Cesta ◽  
Mara Zippoli ◽  
...  
Keyword(s):  
Drug Repurposing ◽  
Pharmaceutical Products ◽  
Clinical Development ◽  
Pharmacological Agent ◽  
Pharmacological Characterization ◽  
Protein Targets ◽  
Drug Candidates ◽  
Cellular Models ◽  
Receptor Modulator

The new coronavirus that emerged, called SARS-CoV-2, is the causative agent of the COVID-19 pandemic. The identification of potential drug candidates that can rapidly enter clinical trials for the prevention and treatment of COVID-19 is an urgent need, despite the recent introduction of several new vaccines for the prevention and protection of this infectious disease which in many cases becomes severe. Drug repurposing (DR), a process for studying existing pharmaceutical products for new therapeutic indications, represents one of the most effective potential strategies employed to increase the success rate in the development of new drug therapies. We identified raloxifene, a known Selective Estrogen Receptor modulator (SERM), as a potential pharmacological agent for the treatment of COVID-19 patients. Following a virtual screening campaign on the most relevant viral protein targets, in this work we report the results of the first pharmacological characterization of raloxifene in relevant cellular models of COVID-19 infection. The results obtained on all the most common viral variants originating in Europe, United Kingdom, Brazil, South Africa and India, currently in circulation, are also reported, confirming the efficacy of raloxifene and, consequently, the relevance of the proposed approach. Taken together, all the information gathered supports the clinical development of raloxifene and confirms that the drug can be proposed as a viable new option to fight the pandemic in at least some patient populations. The results obtained so far have paved the way for a first clinical study to test the safety and efficacy of raloxifene, just concluded in patients with COVID-19 paucisymptomatic.

scholarly journals Organic synthesis: the art and science of replicating the molecules of living nature and creating others like them in the laboratory

2014 ◽  
Vol 470 (2163) ◽  
pp. 20130690 ◽  
Author(s):  
K. C. Nicolaou
Keyword(s):  
Total Synthesis ◽  
Organic Synthesis ◽  
Organic Molecules ◽  
Clinical Development ◽  
Catalytic Reactions ◽  
Bioactive Molecules ◽  
Drug Candidates ◽  
Science Technology ◽  
Potential Applications ◽  
Living Nature

Synthetic organic chemists have the power to replicate some of the most intriguing molecules of living nature in the laboratory and apply their developed synthetic strategies and technologies to construct variations of them. Such molecules facilitate biology and medicine, as they often find uses as biological tools and drug candidates for clinical development. In addition, by employing sophisticated catalytic reactions and appropriately designed synthetic processes, they can synthesize not only the molecules of nature and their analogues, but also myriad other organic molecules for potential applications in many areas of science, technology and everyday life. After a short historical introduction, this article focuses on recent advances in the field of organic synthesis with demonstrative examples of total synthesis of complex bioactive molecules, natural or designed, from the author’s laboratories, and their impact on chemistry, biology and medicine.

Exploring the Multifunctional Neuroprotective Promise of Rasagiline Derivatives for Multi-Dysfunctional Alzheimer’s Disease

2020 ◽  
Vol 26 (37) ◽  
pp. 4690-4698 ◽  
Author(s):  
Md. Sahab Uddin ◽  
Md. Tanvir Kabir ◽  
Md. Habibur Rahman ◽  
Md. Abdul Alim ◽  
Md. Motiar Rahman ◽  
...  
Keyword(s):  
Single Molecule ◽  
Molecular Mechanisms ◽  
Iron Chelator ◽  
Clinical Development ◽  
Drug Candidate ◽  
Brain Disorder ◽  
Neuroprotective Effects ◽  
Drug Candidates ◽  
Age Related ◽  
Over Time

Alzheimer's disease (AD) is a chronic, age-related, and irreversible brain disorder that typically develops slowly and gets worse over time. The potent auspicious drug candidate for the treatment of AD is supposed to perform the simultaneous modulation of several targets linked to AD. The new therapeutic approach involves drug candidates that are designed to act on multiple targets and have various pharmacological properties. This trend has triggered the development of various multimodal drugs including TV-3326 (i.e. ladostigil) and M-30 (i.e. a new multitarget iron chelator). TV-3326 combines the neurorestorative/neuroprotective effects of the cholinesterase (ChE) inhibitory activity of rivastigmine with rasagiline (a selective monoamine oxidase-B inhibitor and novel antiparkinsonian agent) in a single molecule. M-30, the second derivative of rasagiline, was developed by combining the propargyl moiety of rasagiline into the skeleton of VK-28 (i.e. a novel brain permeable neuroprotective iron chelator). It has been revealed that both the compounds possess anti-AD effects and therefore, the clinical development is directed to the treatment of this type of neurodegenerative diseases (NDs). In this article, we have reviewed the neuroprotective molecular mechanisms and multimodal effects of TV-3326 and M-30.

Sign in / Sign up

Export Citation Format

Share Document