Four lessons from global health drug discovery: medicine for an ailing industry?
Ontology highlight
ABSTRACT:
SUBMITTER: Elliott RL
PROVIDER: S-EPMC4025862 | biostudies-other | 2012 Sep
REPOSITORIES: biostudies-other
Similar Datasets
Project description:In 2008, the UCLA Department of Medicine established a three-week clinical elective in Malawi, Africa, for Medicine and Medicine/Pediatrics residents. We sought to determine whether the elective resulted in improved medical knowledge, alterations in career trajectory, and whether the opportunity for the elective influenced selection of UCLA for residency. A 29-question survey was distributed to all graduates of the elective from 2009-2013. Surveys were distributed to 40 individuals, with 33 responses (82.5%). Thirty-one participants (93.9%) reported increased medical knowledge and 24 participants (72.7%) reported the rotation altered their career trajectory. Among the 23 residents who came to UCLA after the elective was established, 13 (56.5%) stated it had an influential role in their selection of UCLA for residency. The Malawi elective resulted in self-reported increases in medical knowledge, alterations in career trajectory, and has played an important role in attracting individuals to UCLA for residency.
| S-EPMC4228879 | biostudies-other
Project description:Despite massive global efforts tuberculosis rates continue to climb and drug-resistance rates are rising to alarming levels. Discovering new agents for treating this bacterial pathogen poses unique challenges, but these challenges have been faced throughout the entire modern history of research into anti-infectives. This review looks back at every decade since the 1940s and summarizes the most important drugs developed during each decade highlighting the lessons learned during these successful medicinal chemistry programs. Looking forward we must accelerate the integration of these past lessons with the impressive advances that have been made in the basic understanding of the biology of this disease.
| S-EPMC6380367 | biostudies-literature
Project description:During the coronavirus disease 2019 (COVID-19) pandemic, a wave of rapid and collaborative drug discovery efforts took place in academia and industry, culminating in several therapeutics being discovered, approved and deployed in a 2-year time frame. This article summarizes the collective experience of several pharmaceutical companies and academic collaborations that were active in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral discovery. We outline our opinions and experiences on key stages in the small-molecule drug discovery process: target selection, medicinal chemistry, antiviral assays, animal efficacy and attempts to pre-empt resistance. We propose strategies that could accelerate future efforts and argue that a key bottleneck is the lack of quality chemical probes around understudied viral targets, which would serve as a starting point for drug discovery. Considering the small size of the viral proteome, comprehensively building an arsenal of probes for proteins in viruses of pandemic concern is a worthwhile and tractable challenge for the community.
| S-EPMC10176316 | biostudies-literature
Project description:Global health networks, webs of individuals and organizations with a shared concern for a particular condition, have proliferated over the past quarter century. They differ in their effectiveness, a factor that may help explain why resource allocations vary across health conditions and do not correspond closely with disease burden. Drawing on findings from recently concluded studies of eight global health networks-addressing alcohol harm, early childhood development (ECD), maternal mortality, neonatal mortality, pneumonia, surgically-treatable conditions, tobacco use, and tuberculosis-I identify four challenges that networks face in generating attention and resources for the conditions that concern them. The first is problem definition: generating consensus on what the problem is and how it should be addressed. The second is positioning: portraying the issue in ways that inspire external audiences to act. The third is coalition-building: forging alliances with these external actors, particularly ones outside the health sector. The fourth is governance: establishing institutions to facilitate collective action. Research indicates that global health networks that effectively tackle these challenges are more likely to garner support to address the conditions that concern them. In addition to the effectiveness of networks, I also consider their legitimacy, identifying reasons both to affirm and to question their right to exert power.
| S-EPMC5384980 | biostudies-other
Project description:Analysis of binding energy hot spots at protein surfaces can provide crucial insights into the prospects for successful application of fragment-based drug discovery (FBDD), and whether a fragment hit can be advanced into a high-affinity, drug-like ligand. The key factor is the strength of the top ranking hot spot, and how well a given fragment complements it. We show that published data are sufficient to provide a sophisticated and quantitative understanding of how hot spots derive from a protein 3D structure, and how their strength, number, and spatial arrangement govern the potential for a surface site to bind to fragment-sized and larger ligands. This improved understanding provides important guidance for the effective application of FBDD in drug discovery.
| S-EPMC4640985 | biostudies-literature
Project description:Many drugs, or their antecedents, were discovered through observation of their effects on normal or disease physiology. For the past generation, this phenotypic drug discovery approach has been largely supplanted by the powerful but reductionist approach of modulating specific molecular targets of interest. Nevertheless, modern phenotypic drug discovery, which combines the original concept with modern tools and strategies, has re-emerged over the past decade to systematically pursue drug discovery based on therapeutic effects in realistic disease models. Here, we discuss recent successes with this approach, as well as consider ongoing challenges and approaches to address them. We also explore how innovation in this area may fuel the next generation of successful projects.
| S-EPMC9708951 | biostudies-literature
Project description:Organisation EGAO00000000867
| EGAO00000000867 | EGA
Project description:The development of structure-guided drug discovery is a story of knowledge exchange where new ideas originate from all parts of the research ecosystem. Dorothy Crowfoot Hodgkin obtained insulin from Boots Pure Drug Company in the 1930s and insulin crystallization was optimized in the company Novo in the 1950s, allowing the structure to be determined at Oxford University. The structure of renin was developed in academia, on this occasion in London, in response to a need to develop antihypertensives in pharma. The idea of a dimeric aspartic protease came from an international academic team and was discovered in HIV; it eventually led to new HIV antivirals being developed in industry. Structure-guided fragment-based discovery was developed in large pharma and biotechs, but has been exploited in academia for the development of new inhibitors targeting protein-protein interactions and also antimicrobials to combat mycobacterial infections such as tuberculosis. These observations provide a strong argument against the so-called 'linear model', where ideas flow only in one direction from academic institutions to industry. Structure-guided drug discovery is a story of applications of protein crystallography and knowledge exhange between academia and industry that has led to new drug approvals for cancer and other common medical conditions by the Food and Drug Administration in the USA, as well as hope for the treatment of rare genetic diseases and infectious diseases that are a particular challenge in the developing world.
| S-EPMC5571795 | biostudies-literature
Project description:ContextIn recent decades, natural products have undisputedly played a leading role in the development of novel medicines. Yet, trends in the pharmaceutical industry at the level of research investments indicate that natural product research is neither prioritized nor perceived as fruitful in drug discovery programmes as compared with incremental structural modifications and large volume HTS screening of synthetics.AimWe seek to understand this phenomenon through insights from highly experienced natural product experts in industry and academia.MethodWe conducted a survey including a series of qualitative and quantitative questions related to current insights and prospective developments in natural product drug development. The survey was completed by a cross-section of 52 respondents in industry and academia.ResultsOne recurrent theme is the dissonance between the perceived high potential of NP as drug leads among individuals and the survey participants' assessment of the overall industry and/or company level strategies and their success. The study's industry and academic respondents did not perceive current discovery efforts as more effective as compared with previous decades, yet industry contacts perceived higher hit rates in HTS efforts as compared with academic respondents. Surprisingly, many industry contacts were highly critical to prevalent company and industry-wide drug discovery strategies indicating a high level of dissatisfaction within the industry.ConclusionsThese findings support the notion that there is an increasing gap in perception between the effectiveness of well established, commercially widespread drug discovery strategies between those working in industry and academic experts. This research seeks to shed light on this gap and aid in furthering natural product discovery endeavors through an analysis of current bottlenecks in industry drug discovery programmes.
| S-EPMC4620409 | biostudies-literature
Project description:BackgroundSecondary fungal metabolites are important sources for new drugs against infectious diseases and cancers.MethodsTo obtain a library with enough diversity, we collected about 2,395 soil samples and 2,324 plant samples from 36 regions in Africa, Asia, and North America. The collection areas covered various climate zones in the world. We examined the usability of the global fungal extract library (GFEL) against parasitic malaria transmission, Gram-positive and negative bacterial pathogens, and leukemia cells.ResultsNearly ten thousand fungal strains were isolated. Sequences of nuclear ribosomal internal transcribed spacer (ITS) from 40 randomly selected strains showed that over 80% were unique. Screening GFEL, we found that the fungal extract from Penicillium thomii was able to block Plasmodium falciparum transmission to Anopheles gambiae, and the fungal extract from Tolypocladium album was able to kill myelogenous leukemia cell line K562. We also identified a set of candidate fungal extracts against bacterial pathogens.
| S-EPMC7703384 | biostudies-literature