scholarly journals The academic model: Drug discovery in the academic environment

2012 ◽  
Vol 34 (1) ◽  
pp. 4-6
Author(s):  
Peter R. Shepherd ◽  
William A. Denny
Keyword(s):  
Chemical Space ◽  
New Drugs ◽  
Scientific Methods ◽  
Chemical Structures ◽  
Drug Companies ◽  
Wide Range ◽  
Life Threatening ◽  
Model Drug ◽  
To Come ◽  
The Cost

The second half of the 20th Century was a golden age for the pharmaceutical industry, as ever increasingly sophisticated scientific methods were applied to the process of discovering new drugs and then developing them through the pre-clinical and clinical phases. This was very fruitful, scientifically and financially, with a wide range of highly successful new drugs being developed. These included blockbusters such as the very effective cholesterol-lowering drugs such as Lipitor®, which contributed significantly to the reduced rates of mortality from cardiovascular disease, through to drugs such as Viagra® that treated less life-threatening, but socially important, conditions. In the 1970s and 1980s, the pharma industry employed a high percentage of biochemistry graduates and provided jobs that paid well and seemed to have good security. Inevitably, however, as the older blockbusters began to come off patent, a technological ‘arms race’ broke out as companies searched randomly further and further into chemical space to find chemical structures that might be the elusive new blockbuster drug. Companies built bigger and bigger libraries of drugs, in many cases containing more than a million compounds. These required impressive assay technology and massive robotic screens to sift through. At the same time, the cost of getting drugs to market was increasing due to ever-tightening safety regulations, and, despite the application of ever more technology, the failure rate in (and after) clinical trial remained stubbornly high.

The Economics of New Drugs: Can We Afford to Make Progress in a Common Disease?

2013 ◽  
pp. e126-e130
Author(s):  
Bradford R. Hirsch ◽  
Kevin A. Schulman
Keyword(s):  
Drug Development ◽  
Cost Of Capital ◽  
New Drugs ◽  
Common Disease ◽  
Target Market ◽  
Sustainable Business ◽  
Product Pricing ◽  
Grant Support ◽  
To Come ◽  
The Cost

The concept of personalized medicine is beginning to come to fruition, but the cost of drug development is untenable today. To identify new initiatives that would support a more sustainable business model, the economics of drug development are analyzed, including the cost of drug development, cost of capital, target market size, returns to innovators at the product and firm levels, and, finally, product pricing. We argue that a quick fix is not available. Instead, a rethinking of the entire pharmaceutical development process is needed from the way that clinical trials are conducted, to the role of biomarkers in segmenting markets, to the use of grant support, and conditional approval to decrease the cost of capital. In aggregate, the opportunities abound.

Pharmaceutical Promotion in Canada: Convince Them or Confuse Them

1987 ◽  
Vol 17 (1) ◽  
pp. 77-89 ◽  
Author(s):  
Joel Lexchin
Keyword(s):  
Medical Profession ◽  
The Public ◽  
Adverse Health Effects ◽  
Drug Companies ◽  
Public Media ◽  
Pharmaceutical Promotion ◽  
The Government ◽  
To Come ◽  
Cost Of Drugs ◽  
The Cost

Currently, drug companies are spending in excess of $200 million annually on promoting their products to Canadian physicians. Although the industry has adopted a voluntary code of advertising practice, this has not prevented gross excesses in all forms of pharmaceutical promotion: drug-company sponsored continuing medical education, and promotion through the public media, detailers, direct mail, sampling, and journal advertising. Not only does advertising add to the cost of drugs, but physicians' reliance on information conveyed through advertising leads to poor prescribing and consequently to significant adverse health effects for patients. Reforms of promotional practices are possible, but the initiative is unlikely to come from either the medical profession or the government. Pressure applied through an emerging grass-roots movement is the best hope for change.

scholarly journals High-Content Screening of Natural Products Reveals Novel Nuclear Export Inhibitors

2013 ◽  
Vol 19 (1) ◽  
pp. 57-65 ◽  
Author(s):  
Bastien Cautain ◽  
Nuria de Pedro ◽  
Virginia Murillo Garzón ◽  
María Muñoz de Escalona ◽  
Victor González Menéndez ◽  
...  
Keyword(s):  
Natural Products ◽  
Nuclear Export ◽  
Chemical Space ◽  
Biological Activities ◽  
Tumor Formation ◽  
New Drugs ◽  
Inhibition Activity ◽  
Nucleocytoplasmic Trafficking ◽  
Active Metabolites ◽  
Chemical Structures

Natural products are considered an extremely valuable source for the discovery of new drugs against diverse pathologies. As yet, we have only explored a fraction of the diversity of bioactive compounds, and opportunities for discovering new natural products leading to new drugs are huge. In the present study, U2nesRELOC, a previously established cell-based imaging assay, was employed to screen a collection of extracts of microbial origin for nuclear export inhibition activity. The fluorescent signal of untreated U2nesRELOC cells localizes predominantly to the cytoplasm. Upon treatment with the nuclear export inhibitor leptomycin B, the fluorescent-tagged reporter proteins appear as speckles in the nucleus. A proprietary collection of extracts from fungi, actinomycetes, and unicellular bacteria that covers an uncommonly broad chemical space was used to interrogate this nuclear export assay system. A two-step image-based analysis allowed us to identify 12 extracts with biological activities that are not associated with previously known active metabolites. The fractionation and structural elucidation of active compounds revealed several chemical structures with nuclear export inhibition activity. Here we show that substrates of the nuclear export receptor CRM1, such as Rev, FOXO3a and NF-κB, accumulate in the nucleus in the presence of the fungal metabolite MDN-0105 with an IC50 value of 3.4 µM. Many important processes in tumor formation and progression, as well as in many viral infections, critically depend on the nucleocytoplasmic trafficking of proteins and RNA molecules. Therefore, the disruption of nuclear export is emerging as a novel therapeutic approach with enormous clinical potential. Our work highlights the potential of applying high-throughput phenotypic imaging on natural product extracts to identify novel nuclear export inhibitors.

IMPROVEMENT OF INNOVATIVE ACTIVITY OF THE ENTERPRISE

2017 ◽  
Author(s):  
Nataliya Stoyanets ◽  
◽  
Mathias Onuh Aboyi ◽  
Keyword(s):  
Value Chain ◽  
Net Present Value ◽  
Successful Implementation ◽  
Innovative Development ◽  
Technological Equipment ◽  
Alliance Partner ◽  
Innovation Potential ◽  
Wide Range ◽  
Technological Platform ◽  
The Cost

The article defines that for the successful implementation of an innovative project and the introduction of a new product into production it is necessary to use advanced technologies and modern software, which is an integral part of successful innovation by taking into account the life cycle of innovations. It is proposed to consider the general potential of the enterprise through its main components, namely: production and technological, scientific and technical, financial and economic, personnel and actual innovation potential. Base for the introduction of technological innovations LLC "ALLIANCE- PARTNER", which provides a wide range of support and consulting services, services in the employment market, tourism, insurance, translation and more. To form a model of innovative development of the enterprise, it is advisable to establish the following key aspects: the system of value creation through the model of cooperation with partners and suppliers; creating a value chain; technological platform; infrastructure, determine the cost of supply, the cost of activities for customers and for the enterprise as a whole. The system of factors of influence on formation of model of strategic innovative development of the enterprise is offered. The expediency of the cost of the complex of technological equipment, which is 6800.0 thousand UAH, is economically calculated. Given the fact that the company plans to receive funds under the program of socio-economic development of Sumy region, the evaluation of the effectiveness of the innovation project, the purchase of technological equipment, it is determined that the payback period of the project is 3 years 10 months. In terms of net present value (NPV), the project under study is profitable. The project profitability index (PI) meets the requirements for a positive decision on project implementation> 1.0. The internal rate of return of the project (IRR) also has a positive value of 22% because it exceeds the discount rate.

General Cyclopropane Assembly via Enantioselective Redox-Active Carbene Transfer to Aliphatic Olefins

2018 ◽  
Author(s):  
Marc Montesinos-Magraner ◽  
Matteo Costantini ◽  
Rodrigo Ramirez-Contreras ◽  
Michael E. Muratore ◽  
Magnus J. Johansson ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Asymmetric Synthesis ◽  
Chemical Space ◽  
Synthetic Approach ◽  
Asymmetric Cyclopropanation ◽  
Redox Active ◽  
Wide Range ◽  
Leaving Group ◽  
Stereoelectronic Properties ◽  
Carbene Transfer

Asymmetric cyclopropane synthesis currently requires bespoke strategies, methods, substrates and reagents, even when targeting similar compounds. This limits the speed and chemical space available for discovery campaigns. Here we introduce a practical and versatile diazocompound, and we demonstrate its performance in the first unified asymmetric synthesis of functionalized cyclopropanes. We found that the redox-active leaving group in this reagent enhances the reactivity and selectivity of geminal carbene transfer. This effect enabled the asymmetric cyclopropanation of a wide range of olefins including unactivated aliphatic alkenes, enabling the 3-step total synthesis of (–)-dictyopterene A. This unified synthetic approach delivers high enantioselectivities that are independent of the stereoelectronic properties of the functional groups transferred. Our results demonstrate that orthogonally-differentiated diazocompounds are viable and advantageous equivalents of single-carbon chirons<i>.</i>

Therapeutic Properties of Several Chemical Compounds from Salvia officinalis L. in Alzheimer’s Disease

2020 ◽  
Vol 21 ◽  
Author(s):  
Georgiana Uță ◽  
Denisa Ștefania Manolescu ◽  
Speranța Avram
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Side Effects ◽  
Chemical Compounds ◽  
Natural Compounds ◽  
Salvia Officinalis ◽  
Chemical Structures ◽  
In Silico Studies ◽  
Wide Range ◽  
Salvia Officinalis L

Background.: Currently, the pharmacological management in Alzheimer's disease is based on several chemical structures, represented by acetylcholinesterase and N-methyl-D-aspartate (NMDA) receptor ligands, with still unclear molecular mechanisms, but severe side effects. For this reason, a challenge for Alzheimer's disease treatment remains to identify new drugs with reduced side effects. Recently, the natural compounds, in particular certain chemical compounds identified in the essential oil of peppermint, sage, grapes, sea buckthorn, have increased interest as possible therapeutics. Objectives.: In this paper, we have summarized data from the recent literature, on several chemical compounds extracted from Salvia officinalis L., with therapeutic potential in Alzheimer's disease. Methods.: In addition to the wide range of experimental methods performed in vivo and in vitro, also we presented some in silico studies of medicinal compounds. Results. Through this mini-review, we present the latest information regarding the therapeutic characteristics of natural compounds isolated from Salvia officinalis L. in Alzheimer's disease. Conclusion.: Thus, based on the information presented, we can say that phytotherapy is a reliable therapeutic method in a neurodegenerative disease.

The Chemistry of Drugs to Treat Candida albicans

2019 ◽  
Vol 19 (28) ◽  
pp. 2554-2566 ◽  
Author(s):  
Aurelio Ortiz ◽  
Estibaliz Sansinenea
Keyword(s):  
Candida Species ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Drug Classes ◽  
Life Threatening ◽  
Antifungal Substances ◽  
High Level ◽  
Systemic Infections ◽  
New Compounds ◽  
Level Resistance

Background:: Candida species are in various parts of the human body as commensals. However, they can cause local mucosal infections and, sometimes, systemic infections in which Candida species can spread to all major organs and colonize them. Objective:: For the effective treatment of the mucosal infections and systemic life-threatening fungal diseases, a considerably large number of antifungal drugs have been developed and used for clinical purposes that comprise agents from four main drug classes: the polyenes, azoles, echinocandins, and antimetabolites. Method: : The synthesis of some of these drugs is available, allowing synthetic modification of the molecules to improve the biological activity against Candida species. The synthetic methodology for each compound is reviewed. Results: : The use of these compounds has caused a high-level resistance against these drugs, and therefore, new antifungal substances have been described in the last years. The organic synthesis of the known and new compounds is reported. Conclusion: : This article summarizes the chemistry of the existing agents, both the old drugs and new drugs, in the treatment of infections due to C. albicans, including the synthesis of the existing drugs.

Advances in Triazole Synthesis from Copper-catalyzed Azide-alkyne Cycloadditions (CuAAC) Based on Eco-friendly Procedures

2019 ◽  
Vol 16 (2) ◽  
pp. 244-257 ◽  
Author(s):  
Marcus Vinicius Nora de Souza ◽  
Cristiane França da Costa ◽  
Victor Facchinetti ◽  
Claudia Regina Brandão Gomes ◽  
Paula Mázala Pacheco
Keyword(s):  
Biological Activities ◽  
Reaction Times ◽  
Water Extract ◽  
Fish Bone ◽  
New Drugs ◽  
Bone Powder ◽  
Wide Range ◽  
Recoverable Catalysts ◽  
Egg Shell ◽  
Work Up

Background: 1,2,3-triazoles are an important class of organic compounds and because of their aromatic stability, they are not easily reduced, oxidized or hydrolyzed in acidic and basic environments. Moreover, 1,2,3-triazole derivatives are known by their important biological activities and have drawn considerable attention due to their variety of properties. The synthesis of this nucleus, based on the click chemistry concept, through the 1,3-dipolar addition reaction between azides and alkynes is a well-known procedure. This reaction has a wide range of applications, especially on the development of new drugs. Methods: The most prominent eco-friendly methods for the synthesis of triazoles under microwave irradiation published in articles from 2012-2018 were reviewed. Results: In this review, we cover some of the recent eco-friendly CuAAC procedures for the click synthesis of 1,2,3-triazoles with remarks to new and easily recoverable catalysts, such as rhizobial cyclic β-1,2 glucan; WEB (water extract of banana); biosourced cyclosophoraose (CyS); egg shell powder (ESP); cyclodextrin (β- CD); fish bone powder; nanoparticle-based catalyst, among others. Conclusion: These eco-friendly procedures are a useful tool for the synthesis of 1,2,3-triazoles, providing many advantages on the synthesis of this class, such as shorter reaction times, easier work-up and higher yields when compared to classical procedures. Moreover, these methodologies can be applied to the industrial synthesis of drugs and to other areas.

Synthesis and Biological Evaluation of Novel 4,5,6,7-Tetrahydrobenzo[D]-Thiazol-2- Yl Derivatives Derived from Dimedone with Anti-Tumor, C-Met, Tyrosine Kinase and Pim-1 Inhibitions

2019 ◽  
Vol 19 (12) ◽  
pp. 1438-1453 ◽  
Author(s):  
Rafat M. Mohareb ◽  
Amr S. Abouzied ◽  
Nermeen S. Abbas
Keyword(s):  
Tyrosine Kinase ◽  
Tumor Cell ◽  
Cell Lines ◽  
Single Molecule ◽  
Anticancer Agents ◽  
Biological Evaluation ◽  
New Drugs ◽  
Tumor Cell Lines ◽  
Thiazole Derivatives ◽  
Wide Range

Background: Dimedone and thiazole moieties are privileged scaffolds (acting as primary pharmacophores) in many compounds that are useful to treat several diseases, mainly tropical infectious diseases. Thiazole derivatives are a very important class of compounds due to their wide range of pharmaceutical and therapeutic activities. On the other hand, dimedone is used to synthesize many therapeutically active compounds. Therefore, the combination of both moieties through a single molecule to produce heterocyclic compounds will produce excellent anticancer agents. Objective: The present work reports the synthesis of 47 new substances belonging to two classes of compounds: Dimedone and thiazoles, with the purpose of developing new drugs that present high specificity for tumor cells and low toxicity to the organism. To achieve this goal, our strategy was to synthesize a series of 4,5,6,7-tetrahydrobenzo[d]-thiazol-2-yl derivatives using the reaction of the 2-bromodimedone with cyanothioacetamide. Methods: The reaction of 2-bromodimedone with cyanothioacetamide gave the 4,5,6,7-tetrahydrobenzo[d]- thiazol-2-yl derivative 4. The reactivity of compound 4 towards some chemical reagents was observed to produce different heterocyclic derivatives. Results: A cytotoxic screening was performed to evaluate the performance of the new derivatives in six tumor cell lines. Thirteen compounds were shown to be promising toward the tumor cell lines which were further evaluated toward five tyrosine kinases. Conclusion: The results of antitumor screening showed that many of the tested compounds were of high inhibition towards the tested cell lines. Compounds 6c, 8c, 11b, 11d, 13b, 14b, 15c, 15g, 21b, 21c, 20d and 21d were the most potent compounds toward c-Met kinase and PC-3 cell line. The most promising compounds 6c, 8c, 11b, 11d, 13b, 14b, 15c, 15g, 20c, 20d, 21b, 21c and 21d were further investigated against tyrosine kinase (c-Kit, Flt-3, VEGFR-2, EGFR, and PDGFR). Compounds 6c, 11b, 11d, 14b, 15c, and 20d were selected to examine their Pim-1 kinase inhibition activity the results revealed that compounds 11b, 11d and 15c had high activities.

Bioprospecting Cryptogams as Potential Source of Unique Biodynamic Phytochemicals with Diverse Pharmaceutical Applications

2016 ◽  
Vol 1 (1) ◽  
Author(s):  
Brahma N. Singh ◽  
Garima Pandey ◽  
Prateeksha ◽  
J. Kumar
Keyword(s):  
Secondary Metabolites ◽  
Higher Plants ◽  
New Drugs ◽  
Terrestrial Plants ◽  
Pharmacological Activities ◽  
Therapeutic Drugs ◽  
Potential Source ◽  
Therapeutic Value ◽  
Wide Range ◽  
Novel Structures

With the advent of green pharmaceuticals, the secondary metabolites derived from plants have provided numerous leads for the development of a wide range of therapeutic drugs; however the discovery of new drugs with novel structures has declined in the past few years. Cryptogams including lichens, bryophytes, and pteridophytes represent a group of small terrestrial plants that remain relatively untouched in the drug discovery process though some have been used as ethnomedicines by various tribes worldwide. Studies of their secondary metabolites are recent but reveal unique secondary metabolites which are not synthesized by higher plants. These compounds can have the potential to develop more potential herbal drugs for prevention and treatment of diseases The present article . deals with the secondary metabolites and pharmacological activities of cryptogams with an objective to bring them forth as potential source of biodynamic compounds of therapeutic value.

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