From natural products to drugs

2018 ◽  
Vol 4 (4) ◽  
Author(s):  
David J. Newman
Keyword(s):  
Clinical Trials ◽  
Natural Products ◽  
Natural Product ◽  
Product Structure ◽  
First Century ◽  
Novel Agents ◽  
The Us ◽  
Product Structures ◽  
Twenty First Century ◽  
Us Fda

Abstract It is frequently assumed, particularly in the last 15 plus years, that “Natural Product Structures” are no longer a source of drugs in the twenty-first century. In fact, this is not at all true. Even today, in the search for novel agents against manifold diseases, natural product structures, some quite old and some quite recent, are behind the compounds that are either recently (last 5–10 years) approved or that are now in clinical trials against manifold diseases of man. This chapter will cover agents approved since 2010 to the end of 2017 by the US FDA and its equivalent in other countries, plus selected agents that have entered clinical trials against major diseases such as cancer and infections that have “in their chemical pedigree” a natural product structure, even if the final product may be totally synthetic in nature.

Unzipping Natural Products: Improved Natural Product Structure Predictions by Ensemble Modeling and Fingerprint Matching

2018 ◽  
Author(s):  
William A. Shirley ◽  
Brian P. Kelley ◽  
Yohann Potier ◽  
John H. Koschwanez ◽  
Robert Bruccoleri ◽  
...  
Keyword(s):  
Natural Products ◽  
Open Source ◽  
Natural Product ◽  
Gene Cluster ◽  
Public Domain ◽  
Product Structure ◽  
Fingerprint Matching ◽  
Ensemble Modeling ◽  
Chemical Structures ◽  
Source Gene

This pre-print explores ensemble modeling of natural product targets to match chemical structures to precursors found in large open-source gene cluster repository antiSMASH. Commentary on method, effectiveness, and limitations are enclosed. All structures are public domain molecules and have been reviewed for release.

The Rise and Return of the Indo-Pacific

2019 ◽  
Author(s):  
Timothy Doyle ◽  
Dennis Rumley
Keyword(s):  
Common Ground ◽  
First Century ◽  
Regional Security ◽  
Pacific Region ◽  
Nation States ◽  
The Us ◽  
Us Hegemony ◽  
Twenty First Century ◽  
Under Construction ◽  
Political Realities

In the twenty-first century, the Indo-Pacific region has become the new centre of the world. The concept of the ‘Indo-Pacific’’, though still under construction, is a potentially pivotal site, where various institutions and intellectuals of statecraft are seeking common ground on which to anchor new regional coalitions, alliances, and allies to better serve their respective national agendas. This book explores the Indo-Pacific as an ambiguous and hotly contested regional security construction. It critically examines the major drivers behind the revival of classical geopolitical concepts and their deployment through different national lenses. The book also analyses the presence of India and the US in the Indo-Pacific, and the manner in which China has reacted to their positions in the Indo-Pacific to date. It suggests that national constructions of the Indo-Pacific region are more informed by domestic political realities, anti-Chinese bigotries, distinctive properties of twenty-first century US hegemony, and narrow nation-statist sentiments rather than genuine pan-regional aspirations. The book argues that the spouting of contested depictions of the Indo-Pacific region depend on the fixed geostrategic lenses of nation-states, but what is also important is the re-emergence of older ideas—a classical conceptual revival—based on early to mid-twentieth century geopolitical ideas in many of these countries. The book deliberately raises the issue of the sea and constructions of ‘nature’, as these symbols are indispensable parts of many of these Indo-Pacific regional narratives.

scholarly journals Natural product fragment combination to performance-diverse pseudo-natural products

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Michael Grigalunas ◽  
Annina Burhop ◽  
Sarah Zinken ◽  
Axel Pahl ◽  
José-Manuel Gally ◽  
...  
Keyword(s):  
Natural Products ◽  
Product Design ◽  
Natural Product ◽  
Chemical Space ◽  
Biological Evaluation ◽  
Product Structure ◽  
Biologically Relevant ◽  
Biologically Relevant Chemical Space

AbstractNatural product structure and fragment-based compound development inspire pseudo-natural product design through different combinations of a given natural product fragment set to compound classes expected to be chemically and biologically diverse. We describe the synthetic combination of the fragment-sized natural products quinine, quinidine, sinomenine, and griseofulvin with chromanone or indole-containing fragments to provide a 244-member pseudo-natural product collection. Cheminformatic analyses reveal that the resulting eight pseudo-natural product classes are chemically diverse and share both drug- and natural product-like properties. Unbiased biological evaluation by cell painting demonstrates that bioactivity of pseudo-natural products, guiding natural products, and fragments differ and that combination of different fragments dominates establishment of unique bioactivity. Identification of phenotypic fragment dominance enables design of compound classes with correctly predicted bioactivity. The results demonstrate that fusion of natural product fragments in different combinations and arrangements can provide chemically and biologically diverse pseudo-natural product classes for wider exploration of biologically relevant chemical space.

Feminism

2021 ◽  
pp. 410-426
Author(s):  
Elizabeth Hinson-Hasty
Keyword(s):  
Christian Ethics ◽  
First Century ◽  
Christian Realism ◽  
Disciplinary Boundaries ◽  
Contemporary Christian ◽  
The Us ◽  
The World ◽  
Vulnerable People ◽  
Twenty First Century ◽  
Contemporary Context

This chapter examines three feminist responses to Reinhold Niebuhr’s thought and contemporary Christian Realism—conflict, integration, and conversation. The chapter emphasizes the need for future conversation between feminists, realists, and ethicists across a wide variety of fields with people living in the most vulnerable and precarious economic circumstances in the US and around the world. More attention and exploration of Christian concepts of sin and redemption relevant within the contemporary context are worthy of attention. Fostering more intentional conversation across established disciplinary boundaries and with the world’s most vulnerable people will chart a new course in Christian ethics and nurture a more authentic American moral conscience in light of the greatest moral and theological problems of the twenty-first century.

Luspatercept in the treatment of lower-risk myelodysplastic syndromes

2021 ◽  
Author(s):  
Onyee Chan ◽  
Rami S Komrokji
Keyword(s):  
Clinical Trials ◽  
Myelodysplastic Syndromes ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Safety Data ◽  
Erythroid Differentiation ◽  
Fda Approval ◽  
The Us ◽  
Us Fda ◽  
Terminal Erythroid Differentiation

Transforming growth factor beta (TGF-β) signaling pathway is key to hematopoiesis regulation. Increased activation of this pathway contributes to ineffective terminal erythroid differentiation in myelodysplastic syndromes (MDS). Luspatercept is a novel fusion protein that traps TGF-β ligands preventing them from binding to Type II TGF-β receptors, thereby decreasing phosphorylated SMAD2/3 resulting in the downstream effect of promoting erythropoiesis. Seminal clinical trials using luspatercept, PACE-MD and MEDALIST, demonstrated impressive efficacy in the treatment of transfusion-dependent anemia in intermediate risk or lower MDS had led to the US FDA approval for this indication. This review summarizes luspatercept mechanisms of action, efficacy/safety data supporting its use and ongoing clinical trials in MDS.

Epilogue

2020 ◽  
pp. 314-316
Author(s):  
Jennifer A. Delton
Keyword(s):  
New Economy ◽  
National Association ◽  
First Century ◽  
Political Climate ◽  
Donald Trump ◽  
Fine Line ◽  
The Us ◽  
Business Roundtable ◽  
New Challenges ◽  
Twenty First Century

This concluding chapter discusses the National Association of Manufacturers' (NAM) relevance in contemporary times. It shows that NAM is still a going concern. It has survived and adapted to new circumstances, and it has a purported membership of 14,000. It also keeps a lower profile. NAM is no longer the go-to “voice of business,” but it still partners up with the US Chamber of Commerce and the Business Roundtable. In other ways, however, the current NAM resembles its old historic self, despite the drastically different economic and political climate of the twenty-first century. It continues to promote development, offering seminars, data, and other resources to help new manufacturers navigate the new economy. But NAM also has to contend with new challenges in the twenty-first century, as it walks a fine line with regard to President Donald Trump.

Afterword and Timeline: On Becoming a Citizen

2020 ◽  
pp. 123-150
Author(s):  
Melanie C. Hawthorne
Keyword(s):  
Twentieth Century ◽  
Sexual Orientation ◽  
Gender Norms ◽  
First Century ◽  
National Belonging ◽  
Cultural Assumptions ◽  
The Us ◽  
Gay Pride ◽  
Twenty First Century

Throughout the course of the twentieth century and into the twenty-first, women's claims to citizenship in their own right have gradually been recognized in Europe and the US, though some exceptions still remain (as charted in a parallel chronology). Yet citizenship remains tied to broad cultural assumptions about gender and enforces gender norms. The resurgence of nationalism in the twenty-first century suggests and the success of "gay pride" movements may have shifted shame away from sexual orientation and onto national belonging, but the question remains whether the underlying structural ideological isomorphism has shifted.

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