Science, art and drug discovery: a personal perspective

2000 ◽  
Vol 99 (4) ◽  
pp. 255-260 ◽  
Author(s):  
Simon F. CAMPBELL
Keyword(s):  
Clinical Trials ◽  
Erectile Dysfunction ◽  
Drug Discovery ◽  
New Technologies ◽  
Traditional Approach ◽  
Phosphodiesterase Inhibitor ◽  
Research Programme ◽  
Personal Perspective ◽  
The Impact ◽  
Male Erectile Dysfunction

The research programme that started in 1985 led to the approval of Sildenafil (Viagra®), in 1998, as the first oral treatment for male erectile dysfunction. The initial project objective was the design and synthesis of novel inhibitors of phosphodiesterase that would increase tissue levels of cGMP, and that could be beneficial for the treatment of cardiovascular conditions. Starting from zaprinast, a weak phosphodiesterase inhibitor, computer modelling guided rational medicinal chemistry to achieve significant increases in potency and selectivity for the 5-isoenzyme within a novel series of pyrazolopyrimidinones. Optimization of structure–activity relationships and pharmacokinetic properties led to sildenafil, which proved essentially devoid of cardiovascular activity in clinical trials. However, the emerging role of nitric oxide and cGMP in controlling blood flow in the penis suggested that sildenafil would have a beneficial effect on erectile function. This hypothesis was confirmed by extensive clinical trials in nearly 5000 patients and the Food and Drug Administration approved sildenafil in March 1998 for male erectile dysfunction. Sildenafil is now available in over 100 countries and more than 150 million tablets have been dispensed worldwide. The sildenafil research programme reflects a traditional approach to drug discovery, but pressures to improve productivity have prompted major investments in genome sciences and new technologies. The impact of these initiatives on the drug discovery paradigm will be discussed, particularly with respect to shortening time scales between identifying gene sequences and submitting innovative products for regulatory approval.

Clinical trials — the personal perspective of the research physician?

2020 ◽  
Vol 75 (3) ◽  
pp. 256-263
Author(s):  
Maria Y. Egorova ◽  
Irina A. Shuvalova ◽  
Olga I. Zvonareva ◽  
Igor D. Pimenov ◽  
Olga S. Kobyakova ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Medical Care ◽  
New Technologies ◽  
Healthcare Providers ◽  
Study Drug ◽  
Well Being ◽  
Personal Perspective ◽  
Public And Private ◽  
Factors Affecting ◽  
To Receive

Background. The organization of clinical trials (CTs) requires the participation and coordination of healthcare providers, patients, public and private parties. Obstacles to the participation of any of these groups pose a risk of lowering the potential for the implementation of CTs. Researchers are a key human resource in conducting of CT. Their motivation for participation can have a significant impact on the recruitment and retention of patients, on the quality of the data collected, which determines the overall outcome of the study. Aims to assess the factors affecting the inclusion of Russian physicians-researchers in CT, and to determine their role in relations with patients-participants. Materials and methods. The study was organized as a part of the Russian multicenter face-to-face study. A survey was conducted of researchers from 10 cities of Russia (20172018). The participation in the survey for doctors was anonymous and voluntary. Results. The study involved 78 respondents. Most research doctors highly value the importance of research for science (4,84 0,39), society (4,67 0,46) and slightly lower for participating patients (4,44 0,61). The expectations of medical researchers are related to improving their financial situation and attaining new experience (n = 14; 18,18%). However, the opportunity to work with new technologies of treatment and diagnosis (n = 41; 52,56%) acted as a motivating factor. According to the questionnaire, the vast majority of research doctors (n = 29; 37,18%) believe that the main reason for patients to participate in CT is to receive quality and free medical care. The most significant obstacle to the inclusion of participants in CT was the side effects of the study drug (n = 38; 48,71%). Conclusions. The potential of clinical researchers in Russia is very high. The patient-participant acts for the research doctor as the subject of the study, and not the object, so the well-being of the patient is not indifferent to the doctor. However, the features of the functioning of our health care system form the motivation of doctors-researchers (additional earnings, professional self-development) and the way they perceive the motivation of patients (CT as an opportunity to receive quality medical care).

The Impact of Urinary Incontinence on Male Erectile Dysfunction

2017 ◽  
Vol 14 (5) ◽  
pp. e264 ◽  
Author(s):  
Alexandre Fornari ◽  
Marina Gressler ◽  
Ana Neis ◽  
Isabel Cunha ◽  
Lais Oliveira ◽  
...  
Keyword(s):  
Urinary Incontinence ◽  
Erectile Dysfunction ◽  
The Impact ◽  
Male Erectile Dysfunction

scholarly journals Team Approaches to Developing Innovative Products and Processes

1997 ◽  
Vol 01 (04) ◽  
pp. 333-354 ◽  
Author(s):  
Sally Caird ◽  
Robin Roy ◽  
David Wield
Keyword(s):  
New Technologies ◽  
Research Programme ◽  
Environmental Technology ◽  
Product Cycles ◽  
The United Kingdom ◽  
Innovative Products ◽  
Research Findings ◽  
Functional Teams ◽  
Open Markets ◽  
The Impact

International competitiveness, accelerated by the impact of new technologies, has pressurised industry to meet the challenges for higher productivity, faster product cycles, higher levels of quality and lower costs in increasingly internationalised markets. Multi-functional teams have been heralded as a management solution and an innovative organisational approach to address these challenges. This paper summarises the findings from a research programme which aimed to identify the most appropriate team approaches for co-ordinating innovative product/process developments and for enhancing their success. It is based on case studies of environmental technology projects in 25 companies in the United Kingdom. Team approaches were broadly classified as "single-disciplinary", "multi-disciplinary" or "multi-functional" according to members' expertise and innovation function, which could be more or less integrated. The research findings emphasised the diversity of organisational teams which varied according to different projects, organisational, inter-organisational and market conditions, and were more complex when several departments, teams or companies were involved. The findings revealed that multi-functional teams were important in achieving success in open markets, because of their control over appropriate expertise, even though they did not guarantee commercial success. Integrated team approaches were not sufficient for achieving susscess, although most companies regarded their teams as necessary.

scholarly journals Translational precision medicine: an industry perspective

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dominik Hartl ◽  
Valeria de Luca ◽  
Anna Kostikova ◽  
Jason Laramie ◽  
Scott Kennedy ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Drug Discovery ◽  
Precision Medicine ◽  
Paradigm Shift ◽  
Development Process ◽  
New Technologies ◽  
Traditional Approach ◽  
Drug Discovery And Development ◽  
Development Face ◽  
Digital Biomarkers

AbstractIn the era of precision medicine, digital technologies and artificial intelligence, drug discovery and development face unprecedented opportunities for product and business model innovation, fundamentally changing the traditional approach of how drugs are discovered, developed and marketed. Critical to this transformation is the adoption of new technologies in the drug development process, catalyzing the transition from serendipity-driven to data-driven medicine. This paradigm shift comes with a need for both translation and precision, leading to a modern Translational Precision Medicine approach to drug discovery and development. Key components of Translational Precision Medicine are multi-omics profiling, digital biomarkers, model-based data integration, artificial intelligence, biomarker-guided trial designs and patient-centric companion diagnostics. In this review, we summarize and critically discuss the potential and challenges of Translational Precision Medicine from a cross-industry perspective.

scholarly journals Suppression of Nonsense Mutations by New Emerging Technologies

2020 ◽  
Vol 21 (12) ◽  
pp. 4394 ◽  
Author(s):  
Pedro Morais ◽  
Hironori Adachi ◽  
Yi-Tao Yu
Keyword(s):  
Clinical Trials ◽  
New Technologies ◽  
Genetic Disorders ◽  
Protein Translation ◽  
Premature Termination Codon ◽  
Nonsense Suppression ◽  
Coding Region ◽  
Nucleotide Substitutions ◽  
Nonsense Mutations ◽  
The Impact

Nonsense mutations often result from single nucleotide substitutions that change a sense codon (coding for an amino acid) to a nonsense or premature termination codon (PTC) within the coding region of a gene. The impact of nonsense mutations is two-fold: (1) the PTC-containing mRNA is degraded by a surveillance pathway called nonsense-mediated mRNA decay (NMD) and (2) protein translation stops prematurely at the PTC codon, and thus no functional full-length protein is produced. As such, nonsense mutations result in a large number of human diseases. Nonsense suppression is a strategy that aims to correct the defects of hundreds of genetic disorders and reverse disease phenotypes and conditions. While most clinical trials have been performed with small molecules, there is an increasing need for sequence-specific repair approaches that are safer and adaptable to personalized medicine. Here, we discuss recent advances in both conventional strategies as well as new technologies. Several of these will soon be tested in clinical trials as nonsense therapies, even if they still have some limitations and challenges to overcome.

Is technological change a devourer of jobs?

2017 ◽  
pp. 111-140 ◽  
Author(s):  
R. Kapeliushnikov
Keyword(s):  
Technological Change ◽  
Critical Analysis ◽  
New Technologies ◽  
Employment Growth ◽  
Foreseeable Future ◽  
Employment Effects ◽  
Technological Unemployment ◽  
Micro Level ◽  
Task Sets ◽  
The Impact

The paper provides a critical analysis of the idea of technological unemployment. The overview of the existing literature on the employment effects of technological change shows that on the micro-level there exists strong and positive relationship between innovations and employment growth in firms; on the sectoral level this correlation becomes ambiguous; on the macro-level the impact of new technologies seems to be positive or neutral. This implies that fears of explosive growth of technological unemployment in the foreseeable future are exaggerated. Our analysis further suggests that new technologies affect mostly the structure of employment rather than its level. Additionally we argue that automation and digitalisation would change mostly task sets within particular occupations rather than distribution of workers by occupations.

Sitagliptin: a potential drug for the treatment of SARS-CoV-2?

2020 ◽  
Author(s):  
Sanaa Bardaweel
Keyword(s):  
Clinical Trials ◽  
Drug Discovery ◽  
Antimalarial Drug ◽  
Drug Repurposing ◽  
Spike Protein ◽  
Diabetic Patients ◽  
Potential Drug ◽  
Chemokine Production ◽  
Drug Discovery And Development ◽  
Sequence Identity

Recently, an outbreak of fatal coronavirus, SARS-CoV-2, has emerged from China and is rapidly spreading worldwide. As the coronavirus pandemic rages, drug discovery and development become even more challenging. Drug repurposing of the antimalarial drug chloroquine and its hydroxylated form had demonstrated apparent effectiveness in the treatment of COVID-19 associated pneumonia in clinical trials. SARS-CoV-2 spike protein shares 31.9% sequence identity with the spike protein presents in the Middle East Respiratory Syndrome Corona Virus (MERS-CoV), which infects cells through the interaction of its spike protein with the DPP4 receptor found on macrophages. Sitagliptin, a DPP4 inhibitor, that is known for its antidiabetic, immunoregulatory, anti-inflammatory, and beneficial cardiometabolic effects has been shown to reverse macrophage responses in MERS-CoV infection and reduce CXCL10 chemokine production in AIDS patients. We suggest that Sitagliptin may be beneficial alternative for the treatment of COVID-19 disease especially in diabetic patients and patients with preexisting cardiovascular conditions who are already at higher risk of COVID-19 infection.

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