scholarly journals Missing Novelty in Drug Development

2021 ◽  
Author(s):  
Joshua Krieger ◽  
Danielle Li ◽  
Dimitris Papanikolaou
Keyword(s):  
Radical Innovation ◽  
Chemical Similarity ◽  
Net Worth ◽  
Drug Candidates ◽  
Pharmaceutical Firms ◽  
External Finance ◽  
Fda Approval ◽  
Novel Drugs ◽  
Positive Shock ◽  
Novel Drug

Abstract We provide evidence that risk aversion leads pharmaceutical firms to underinvest in radical innovation. We introduce a new measure of drug novelty based on chemical similarity and show that firms face a risk-reward trade-off: novel drug candidates are less likely to obtain FDA approval but are based on more valuable patents. Consistent with a simple model of costly external finance, we show that a positive shock to firms’ net worth leads firms to develop more novel drugs. This suggests that even large firms may behave as though they are risk averse, reducing their willingness to investment in potentially valuable radical innovation.

Integrated in Silico Methods for the Design and Optimization of Novel Drug Candidates

Oncology ◽  
2017 ◽  
pp. 434-481
Author(s):  
Nikola Minovski ◽  
Marjana Novič
Keyword(s):  
In Silico ◽  
Comprehensive Overview ◽  
Design And Optimization ◽  
Drug Candidates ◽  
In Silico Drug Design ◽  
Current Trends ◽  
Novel Drugs ◽  
Screening Protocol ◽  
Cost Efficient ◽  
Novel Drug

Although almost fully automated, the discovery of novel, effective, and safe drugs is still a long-term and highly expensive process. Consequently, the need for fleet, rational, and cost-efficient development of novel drugs is crucial, and nowadays the advanced in silico drug design methodologies seem to effectively meet these issues. The aim of this chapter is to provide a comprehensive overview of some of the current trends and advances in the in silico design of novel drug candidates with a special emphasis on 6-fluoroquinolone (6-FQ) antibacterials as potential novel Mycobacterium tuberculosis DNA gyrase inhibitors. In particular, the chapter covers some of the recent aspects of a wide range of in silico drug discovery approaches including multidimensional machine-learning methods, ligand-based and structure-based methodologies, as well as their proficient combination and integration into an intelligent virtual screening protocol for design and optimization of novel 6-FQ analogs.

Integrated in Silico Methods for the Design and Optimization of Novel Drug Candidates

2015 ◽  
pp. 269-317
Author(s):  
Nikola Minovski ◽  
Marjana Novič
Keyword(s):  
In Silico ◽  
Comprehensive Overview ◽  
Design And Optimization ◽  
Drug Candidates ◽  
In Silico Drug Design ◽  
Current Trends ◽  
Novel Drugs ◽  
Screening Protocol ◽  
Cost Efficient ◽  
Novel Drug

Although almost fully automated, the discovery of novel, effective, and safe drugs is still a long-term and highly expensive process. Consequently, the need for fleet, rational, and cost-efficient development of novel drugs is crucial, and nowadays the advanced in silico drug design methodologies seem to effectively meet these issues. The aim of this chapter is to provide a comprehensive overview of some of the current trends and advances in the in silico design of novel drug candidates with a special emphasis on 6-fluoroquinolone (6-FQ) antibacterials as potential novel Mycobacterium tuberculosis DNA gyrase inhibitors. In particular, the chapter covers some of the recent aspects of a wide range of in silico drug discovery approaches including multidimensional machine-learning methods, ligand-based and structure-based methodologies, as well as their proficient combination and integration into an intelligent virtual screening protocol for design and optimization of novel 6-FQ analogs.

scholarly journals Current and promising novel drug candidates against visceral leishmaniasis

2019 ◽  
Vol 91 (8) ◽  
pp. 1385-1404 ◽  
Author(s):  
Rosa M. Reguera ◽  
Yolanda Pérez-Pertejo ◽  
Camino Gutiérrez-Corbo ◽  
Bárbara Domínguez-Asenjo ◽  
César Ordóñez ◽  
...  
Keyword(s):  
Low Income ◽  
Neglected Tropical Diseases ◽  
Zoonotic Diseases ◽  
Low Income Countries ◽  
Drug Candidates ◽  
Novel Drugs ◽  
Early Case ◽  
New Treatments ◽  
Novel Drug ◽  
Early Case Detection

Abstract Leishmaniasis is a group of zoonotic diseases caused by a trypanosomatid parasite mostly in impoverished populations of low-income countries. In their different forms, leishmaniasis is prevalent in more than 98 countries all over the world and approximately 360-million people are at risk. Since no vaccine is currently available to prevent any form of the disease, the control strategy of leishmaniasis mainly relies on early case detection followed by adequate pharmacological treatment that may improve the prognosis and can reduce transmission. A handful of compounds and formulations are available for the treatment of leishmaniasis in humans, but only few of them are currently in use since most of these agents are associated with toxicity problems such as nephrotoxicity and cardiotoxicity in addition to resistance problems. In recent decades, very few novel drugs, new formulations of standard drugs or combinations of them have been approved against leishmaniasis. This review highlights the current drugs and combinations that are used medical practice and recent advances in new treatments against leishmaniasis that were pointed out in the recent 2nd Conference, Global Challenges in Neglected Tropical Diseases, held in San Juan, Puerto Rico in June 2018, emphasizing the plethora of new families of molecules that are bridging the gap between preclinical and first-in-man trials in next future.

Update on MicroRNA-based Treatment Strategies

2021 ◽  
Vol 30 (03) ◽  
pp. 243-250
Author(s):  
Eric Hesse ◽  
Franz Jakob ◽  
Hanna Taipaleenmäki
Keyword(s):  
Treatment Strategies ◽  
Protein Coding ◽  
Therapeutic Implications ◽  
The Public ◽  
Drug Candidates ◽  
Diagnostic Use ◽  
Recent Success ◽  
Novel Approach ◽  
Novel Drugs ◽  
Novel Drug

AbstractThe family of RNAs comprises several members, protein coding mRNAs and a larger group of non-coding RNAs, which include small, approximately 21-25 nucleotides long microRNAs (miRNAs). In addition to an evolving diagnostic use of RNAs, RNA-based drugs are emerging very rapidly in medicine, which is not only -but currently very prominently visible- due to the impressive success of the first-in-class Covid-19 vaccines such as Comirnaty and Moderna (marketed by the companies Biontech/Pfizer and Moderna, respectively). Although administration of RNA-based drugs comes along with several technical obstacles including delivery approaches, the technology is experiencing a breakthrough and technical and conceptual hurdles that may still remain are very likely to be overcome within the near future. It is therefore highly likely that RNA-based pharmacotherapies may revolutionize medicine by improving vaccination concepts but also by providing novel drugs to treat many other conditions like cancer, metabolic- and degenerative diseases and beyond. It is fascinating to witness the rise of such milestones in medicine and is tempting to elaborate which additional accomplishments can be made using this technology towards personalized medicine comprising diagnostic and therapeutic aspects as well as individual drug design.Although the most recent success with mRNA-based and therefore protein coding vaccines currently takes center stage in media and people’s life, other types of RNAs that are less prominent to the public, like non-coding miRNAs, also develop very successfully towards diagnostic and therapeutic purposes. While the diagnostic use of miRNAs was reviewed in another article in this issue (see article from Hackl et al., this issue), this brief review will provide an update on the emerging therapeutic implications of miRNAs. Despite the fact that no miRNA-based drug has yet reached clinical approval, several compounds are in pre-clinical and clinical development for the treatment of various diseases and great progress has been made during the recent years, which also facilitated the establishment of several innovative biotech companies.Several obstacles associated with this novel approach including off-target effects, tissue specificity and delivery systems exist. However, important improvements have already been made and will continue to be made. It can therefore be assumed that treatments using this class of RNA will also further progress and stimulate additional stakeholders to enter the field to develop novel drug candidates as first-in-class medicinal products to address highly unmet clinical needs. This technology is still at its infancy given that miRNAs were uncovered just about 20 years ago but the conditions are promising for the development of next generation miRNA-based drugs.

Current Status in the Design and Development of Agonists and Antagonists of Adenosine A3 Receptor as Potential Therapeutic Agents

2019 ◽  
Vol 25 (25) ◽  
pp. 2772-2787 ◽  
Author(s):  
Raghu P. Mailavaram ◽  
Omar H.A. Al-Attraqchi ◽  
Supratik Kar ◽  
Shinjita Ghosh
Keyword(s):  
Drug Target ◽  
Therapeutic Agents ◽  
G Protein Coupled Receptors ◽  
Current Status ◽  
Renal Diseases ◽  
Adenosine A3 Receptor ◽  
Drug Candidates ◽  
Novel Drugs ◽  
The Family ◽  
G Protein Coupled

Adenosine receptors (ARs) belongs to the family of G-protein coupled receptors (GPCR) that are responsible for the modulation of a wide variety of physiological functions. The ARs are also implicated in many diseases such as cancer, arthritis, cardiovascular and renal diseases. The adenosine A3 receptor (A3AR) has emerged as a potential drug target for the progress of new and effective therapeutic agents for the treatment of various pathological conditions. This receptor’s involvement in many diseases and its validity as a target has been established by many studies. Both agonists and antagonists of A3AR have been extensively investigated in the last decade with the goal of developing novel drugs for treating diseases related to immune disorders, inflammation, cancer, and others. In this review, we shall focus on the medicinal chemistry of A3AR ligands, exploring the diverse chemical classes that have been projected as future leading drug candidates. Also, the recent advances in the therapeuetic applications of A3AR ligands are highlighted.

Introduction

2017 ◽  
Author(s):  
Stefan Homburg
Keyword(s):  
Great Recession ◽  
Rational Expectations ◽  
Borrowing Constraints ◽  
Distinctive Features ◽  
Net Worth ◽  
The Great Recession ◽  
External Finance ◽  
International Audience ◽  
Aims And Scope

Chapter 1 describes the book’s aims and scope. The main objective is to improve understanding of the Great Recession and its aftermath. The book provides a unified theoretical framework that uses dynamic general equilibrium models, or DGE, but dispenses with the rational expectations assumption. Its distinctive features are clean models with a rich institutional structure encompassing credit money, external finance, borrowing constraints, net worth, real estate, and commercial banks. Written for economists in universities, governments, and financial institutions, the book addresses an international audience.

scholarly journals Integrated network analysis identifying potential novel drug candidates and targets for Parkinson's disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pusheng Quan ◽  
Kai Wang ◽  
Shi Yan ◽  
Shirong Wen ◽  
Chengqun Wei ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drug Target ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Control Group ◽  
Drug Candidates ◽  
Novel Drug

AbstractThis study aimed to identify potential novel drug candidates and targets for Parkinson’s disease. First, 970 genes that have been reported to be related to PD were collected from five databases, and functional enrichment analysis of these genes was conducted to investigate their potential mechanisms. Then, we collected drugs and related targets from DrugBank, narrowed the list by proximity scores and Inverted Gene Set Enrichment analysis of drug targets, and identified potential drug candidates for PD treatment. Finally, we compared the expression distribution of the candidate drug-target genes between the PD group and the control group in the public dataset with the largest sample size (GSE99039) in Gene Expression Omnibus. Ten drugs with an FDR < 0.1 and their corresponding targets were identified. Some target genes of the ten drugs significantly overlapped with PD-related genes or already known therapeutic targets for PD. Nine differentially expressed drug-target genes with p < 0.05 were screened. This work will facilitate further research into the possible efficacy of new drugs for PD and will provide valuable clues for drug design.

Developing novel chemical entities for the treatment of lysosomal storage disorders: an academic perspective

2015 ◽  
Vol 309 (12) ◽  
pp. F996-F999 ◽  
Author(s):  
James A. Shayman
Keyword(s):  
Drug Targets ◽  
Lysosomal Storage ◽  
Federal Drug Administration ◽  
Drug Candidates ◽  
Gaucher Disease Type 1 ◽  
Biotechnology Companies ◽  
Approved Drugs ◽  
Novel Drug ◽  
Early Drug

Historically, most Federal Drug Administration-approved drugs were the result of “in-house” efforts within large pharmaceutical companies. Over the last two decades, this paradigm has steadily shifted as the drug industry turned to startups, small biotechnology companies, and academia for the identification of novel drug targets and early drug candidates. This strategic pivot has created new opportunities for groups less traditionally associated with the creation of novel therapeutics, including small academic laboratories, for engagement in the drug discovery process. A recent example of the successful development of a drug that had its origins in academia is eliglustat tartrate, an oral agent for Gaucher disease type 1.

scholarly journals Harnessing the medicinal properties of Cussonia barteri Seem. (Araliaceae) in drug development. A review

2018 ◽  
Vol 64 (3) ◽  
pp. 50-61 ◽  
Author(s):  
Ighodaro Igbe ◽  
Osaze Edosuyi ◽  
Agbonlahor Okhuarobo
Keyword(s):  
Drug Development ◽  
Antioxidant Activities ◽  
Biological Activities ◽  
Stem Bark ◽  
Deciduous Tree ◽  
Drug Candidates ◽  
Medicinal Properties ◽  
Phytochemical Constituents ◽  
Anti Inflammatory ◽  
Novel Drug

Summary Cussonia barteri Seem (Araliaceae) is a deciduous tree growing in savannah of Africa. Ethnomedicinally, it is used in Africa as an analgesic, anti-malarial, anti-inflammatory, anti-anaemic, anti-diarhoea, anti-poison, ani-pyschotic and anti-epileptic agent. This review provides a brief summary on the phytochemical screenings, ethnomedicinal and pharmacological applications of various parts of C. barteri. Leaves, stem bark and seed of C. barteri have been shown to be rich in saponins, flavonoids, phenols, sugars and alkaloids. Some of these constituents have been isolated and elucidated from C. barteri. Several compounds isolated from plant include triterpenes, saponins, polyenyne and quinic esters. Phytochemical constituents are also partly responsible for biological activities of C. barteri. Extracts and components isolated from the plant have demonstrated neuropharmacological, anti-larvicidal, anti-microbial, anti-inflammatory and antioxidant activities. Overall, the insights provided by this review reinforce the potential of C. barteri for drug development and create the need for further scientific probe of constituents of the plant with the aim of developing novel drug candidates.

scholarly journals PERSPECTIVE INSIGHT AND APPLICATION OF IN-SILICO TOOL AS VIRTUAL SCREENING METHOD FOR LEAD DESIGNING AND DEVELOPMENT

2021 ◽  
Vol 11 (6) ◽  
pp. 16-24
Author(s):  
Hemant U Chikhale
Keyword(s):  
In Silico ◽  
Screening Method ◽  
Lead Discovery ◽  
Environmental Technology ◽  
Lead Structure ◽  
Drug Candidates ◽  
Underlying Principle ◽  
Novel Drug ◽  
Investigative Process ◽  
Specific Illness

Humans are now in a bioinformatics and chemo informatics century, where we can foresee data across domains like as healthcare, the environmental, technology, and public health. The use of information sharing in silico methodologies has impacted sickness administration by predicting the absorption, distribution, metabolism, excretion, and toxicity (ADMET) patterns of synthetic compounds and efficient and environmentally succeeding pharmaceuticals upfront. The purpose of lead discovery and design is to create the appearance of novel drug candidates that can attach to a specific illness cause. The lead investigative process starts with the recognition of the lead structure, which is followed by the synthesis of its analogs and their estimation in order to produce a candidate for lead improvement. The finding of the proper lead exact is the fundamental and primary worked in the traditional lead discovery progression, and the use of computer (in silico) approaches is widely used in lead innovation. A medicinal chemist's passion for building lead structure is piqued by biomolecules, which are often made up of DNA, RNA, and proteins (such as enzymes, receptors, transporters, and ion channels). The underlying principle of such nuts and bolts is noteworthy to be acquainted with their pharmacological implication to the disease under examination. The motive of this review piece of writing is to emphasize several of the in silico methods that are used in lead discovery and to express the applications of these computational methods.

Sign in / Sign up

Export Citation Format

Share Document