The document discusses finding new uses for existing drugs through repurposing or repositioning old drugs. It notes that repurposing drugs can be more cost-effective than developing new drugs and can help address neglected and rare diseases. The document analyzes datasets of drugs identified in in vitro screens to have new biological activities and orphan drugs approved for rare diseases. It finds that drugs identified in screens tend to be more hydrophobic and higher weight than orphan drugs. It advocates for developing better curated databases of drug structures and properties to enable in silico screening for new uses. Overall, the document makes the case that repurposing existing drugs is a promising strategy to develop new treatments, especially for rare and neglected diseases, and that informatics
NIH Drug Discovery and Development - NCTT and CTSAsCTSI at UCSF
Presented at the UC Braid Retreat: Imagine a statewide research engine of pooled resources, data, and expertise that accelerates the “translation” of academic research to direct patient benefit. That's the goal of the University of California Biomedical Research Acceleration, Integration, and Development (UC BRAID) program.
Presenter: Marina Sirota, UCSF
Recent advances in genome typing and sequencing technologies have enabled quick generation of a vast amount of molecular data at very low cost. The mining and computational analysis of this type of data can help shape new diagnostic and therapeutic strategies in biomedicine. In this talk, I will discuss how such technological advances in combination with data science and integrative analysis can be applied to drug discovery in the context of drug target identification, computational drug repurposing, and population stratification approaches.
Disease Network is the science that has emerged to diagnose a disease from a network aspect
specifically. Networks are the group that interconnect to each others similarly disease networks are
the one that reveal concelled connection among apparently independent biomedical entities like
physiologic process, signaling receptors, in addition to genetic code, also they prove to exists
intitutive in addition to powerful way to learn/discover or diagnose a disease.Due to these networks,
we can now consume the elderly drugs and its method to learn/discover the new drug
accordingly.Example- Colchicine is used in gout but after repurposing it is also used in mediterranean
fever. This is because there are many factors that affect the body during mediterranean fever and
gout, we know that gout is a form of arthritis that causes pain in joints also mediterranean fever is the
one which is accompanied by pain in joints, therefore colchicine is used as a repurposed drug again.In
repurposing of medicines or drugs we first analyse the change in symptoms and identify the target
organ and accorgingly we produce a drug that is compatible with pharmacokinetics of the body. As
the availablity of transcriptomic,proteomic and metabolomic data sources are increasing day by day it helps in classification of disease .Also there are some networks reffered to as complex networks which can be called as collection of linked junctions/ nodes
Pistoia Alliance datathon for drug repurposing for rare diseasesPistoia Alliance
As part of the Pistoia Alliance Centre of Excellence for AI in Life Sciences, we are running a datathon.
Rare Disease Drug Repurposing Datathon is your chance to advance knowledge on rare diseases and illustrate best practices in data science. Are you ready to help make a difference — and to showcase your organization’s data science work and skills?
KIF1A.ORG is a parent-led organization established in 2017 to launch the world’s first translational research program dedicated to discovering treatment for people affected by KIF1A Associated Neurological Disorder (KAND). There is no cure or treatment for this neurodegenerative disorder. Yet.
Our organization supports researchers who engage in collaborative and translational work to rapidly discover treatment for this generation of KAND patients. We have made tangible progress over the last three years, but time is running out. 2020 is a transformational year for KIF1A with a clear path to clinical trials.
This Path to Treatment outlines our immediate therapeutic strategy with defined objectives and resources needed to bring treatment options to families affected by KAND.
Learn more and join our mission at www.kif1a.org or contact us at impact@kif1a.org.
While companies no more possesses deep and extensive product pipeline, this is the perfect time to innovate! Innovate not only in terms of product (although that is the core), but also
NIH Drug Discovery and Development - NCTT and CTSAsCTSI at UCSF
Presented at the UC Braid Retreat: Imagine a statewide research engine of pooled resources, data, and expertise that accelerates the “translation” of academic research to direct patient benefit. That's the goal of the University of California Biomedical Research Acceleration, Integration, and Development (UC BRAID) program.
Presenter: Marina Sirota, UCSF
Recent advances in genome typing and sequencing technologies have enabled quick generation of a vast amount of molecular data at very low cost. The mining and computational analysis of this type of data can help shape new diagnostic and therapeutic strategies in biomedicine. In this talk, I will discuss how such technological advances in combination with data science and integrative analysis can be applied to drug discovery in the context of drug target identification, computational drug repurposing, and population stratification approaches.
Disease Network is the science that has emerged to diagnose a disease from a network aspect
specifically. Networks are the group that interconnect to each others similarly disease networks are
the one that reveal concelled connection among apparently independent biomedical entities like
physiologic process, signaling receptors, in addition to genetic code, also they prove to exists
intitutive in addition to powerful way to learn/discover or diagnose a disease.Due to these networks,
we can now consume the elderly drugs and its method to learn/discover the new drug
accordingly.Example- Colchicine is used in gout but after repurposing it is also used in mediterranean
fever. This is because there are many factors that affect the body during mediterranean fever and
gout, we know that gout is a form of arthritis that causes pain in joints also mediterranean fever is the
one which is accompanied by pain in joints, therefore colchicine is used as a repurposed drug again.In
repurposing of medicines or drugs we first analyse the change in symptoms and identify the target
organ and accorgingly we produce a drug that is compatible with pharmacokinetics of the body. As
the availablity of transcriptomic,proteomic and metabolomic data sources are increasing day by day it helps in classification of disease .Also there are some networks reffered to as complex networks which can be called as collection of linked junctions/ nodes
Pistoia Alliance datathon for drug repurposing for rare diseasesPistoia Alliance
As part of the Pistoia Alliance Centre of Excellence for AI in Life Sciences, we are running a datathon.
Rare Disease Drug Repurposing Datathon is your chance to advance knowledge on rare diseases and illustrate best practices in data science. Are you ready to help make a difference — and to showcase your organization’s data science work and skills?
KIF1A.ORG is a parent-led organization established in 2017 to launch the world’s first translational research program dedicated to discovering treatment for people affected by KIF1A Associated Neurological Disorder (KAND). There is no cure or treatment for this neurodegenerative disorder. Yet.
Our organization supports researchers who engage in collaborative and translational work to rapidly discover treatment for this generation of KAND patients. We have made tangible progress over the last three years, but time is running out. 2020 is a transformational year for KIF1A with a clear path to clinical trials.
This Path to Treatment outlines our immediate therapeutic strategy with defined objectives and resources needed to bring treatment options to families affected by KAND.
Learn more and join our mission at www.kif1a.org or contact us at impact@kif1a.org.
While companies no more possesses deep and extensive product pipeline, this is the perfect time to innovate! Innovate not only in terms of product (although that is the core), but also
Exploring Molecular Targets for Repositioning of Hypertensive DrugsYogeshIJTSRD
Drug repositioning or drug repurposing or drug profiling is the discovery of new applications for approved or failed drug.. Drug repositioning is the development of new approved drug applications. The cost of bringing a medicine to the market is around one million which include clinical and preclinical trials. Repositioning of drugs help in cutting down costs as well as time involve in intial validation and authorization. The procedure involved in Drug repositioning is generally performed during the drug development phase to modify or extend an active molecules distribution line. On a fundamental level, repositioning opportunities exist because drugs perturb multiple biological entities and engage themselves in multiple biological processes. Therefore, a drug can play multiple roles or perform a various mode of actions that are responsible for its pharmacology. Hypertension, is a condition that causes increase in the risk of cardiovascular diseases. In this study an attempt has been made to reposition hypertensive drugs for different diseases by exploring molecular targets of hypertensive drugs. Consider that they often need to be administered for long periods of time, often over whole life time Side effects although present, have been found safe enough to be used for such long durations, hence repurposing these drugs for other diseases may be beneficial with limited side effects. Bhawna Singh | Asmita Das "Exploring Molecular Targets for Repositioning of Hypertensive Drugs" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-3 , April 2021, URL: https://www.ijtsrd.com/papers/ijtsrd39910.pdf Paper URL: https://www.ijtsrd.com/biological-science/bioinformatics/39910/exploring-molecular-targets-for-repositioning-of-hypertensive-drugs/bhawna-singh
Learn how to use Pathway Studio to explore biomarkers and brain regions. With the addition of highly sophisticated visualization tools, users can interactively explore the vast number of connections created to help unravel disease biology. In addition, an innovative new taxonomy based on brain region identifications will be presented. Together, these innovations can be applied to rapidly increase the knowledge of diseases based on published findings.
Cell centered database for immunology and cancer research feb252016Ann-Marie Roche
Determining the cellular mechanisms of diseases is a crucial requirement for understanding the causes and progression of diseases, predicting outcomes, and developing new treatments. Often relevant information, e.g. what cells are involved in a disease or what effects does a drug have on cells, is scattered across many papers and journals, which makes it difficult for researchers to be sure they have a complete picture. Using Elsevier’s automated text mining technology, we have created a new cell-centered database consisting of 850 000 facts captured from more than 24 million PubMed abstracts and 3.5 million full text articles for use in Pathway Studio. This database focused primarily on cellular aspects of immunology and immuno-oncology can be used to summarize and visualize published research, and to analyze experimental data.
Developing Drugs in the New Era of Personalized Medicines by Anita Nelsen - Head of Genomic Medicine, Sr. Director, PAREXEL International and Dr. Sy Pretorius - Sr. Vice President, Chief Scientific Officer, PAREXEL International
Many molecules in nature have geometry, which enables
them to exist as non-superimposable mirror images, or enantiomers.
Modulation of toxicity of such molecules provides
possibility for therapeutics, since they target
multiple points in biochemical pathways. It was hypothesized
that toxicity of a chemical agent, could be counteracted
by a homeopathic preparation of the enantiomer of
the chemical agent
BioVariance - Pediatric Pharmacogenomics in Drug DiscoveryJosef Scheiber
This slideset gives an overview of pharmacogenomic and pediatric dosing knowledge and various influence factors. Finally it shows an example on how to use this kind of Data within predictive approaches.
Establishing other new medical usages for already known drugs, including approved drugs.
Drug repurposing lies in repurposing an active pharmaceutical ingredient for a new indication that is already on the market.
Drug repurposing is a promising approach and mainly applied for the treatment of both common and rare genetic diseases, and it also offers significant benefits to the pharmaceutical industries.
"At its simplest, drug repurposing is taking an existing drug and seeing whether it can be used as an effective treatment for another condition.“
“Repurposing generally refers to studying drugs that are already approved to treat one disease or condition to see if they are safe and effective for treating other diseases”.
The slides from the keynote given by Dr. Dan Malone RPh, PhD at the First International Drug-Drug Interaction Knowledge Representation Workshop on October 6th 2014 (http://icbo14.com/sessions/drug-drug-interaction-knowledge-representation-workshop/). Posted with his permission.
Piloting a Comprehensive Knowledge Base for Pharmacovigilance Using Standardi...Richard Boyce, PhD
A presentation of a new adverse drug event evidence base (Laertes - http://goo.gl/nZSqVw) within a standard framework for clinical research (OHDSI - www.ohdsi.org) made at the American Medical Informatics Association Joint Summits on Translational Research on 3/26/2015
This document presents an overview of the AI applications in life sciences. The presentation highlights various steps in drug development and AI applications. Also, discusses Alzheimer’s disease and obstacles to develop drugs. Finally, presents details of AI in target identification for AD.
This disclaimer informs readers know that the views, thoughts, and opinions expressed in the presentation belong solely to the author, and not to the author’s employer, organization, committee or other group or individual.
Clustering the royal society of chemistry chemical repository to enable enhan...Valery Tkachenko
The Royal Society of Chemistry has hosted the ChemSpider database and associated platforms for over five years. Technologies made significant progress over that period but, more importantly, the community needs in terms of the variety of data types as well as search performance have increased. The preprocessing of chemicals for improved similarity searching and compound database navigation is seen as one crucial component of major development efforts to architect a new data repository. This component is engineered and implemented in collaboration with the group of Professor Oliver Kohlbacher at University of Tübingen. They have developed an approach for clustering large chemical libraries based on a fast, parallel, and purely CPU-based algorithm for 2D binary fingerprint similarity calculation. Using this method, the complete similarity network of our seed set with tens of millions of chemicals has been analyzed at a Tanimoto threshold of 0.6 and all similarity links were fed into our database. The latter is highly beneficial and will allow us to create more complex and enriching visualizations of similar compounds with associated bioactivity data and physicochemical properties for the RSC chemical repository users. This presentation will provide an overview of our experiences in applying clustering to our compound data and how it will be used to enrich data navigation on the RSC data repository.
Exploring Molecular Targets for Repositioning of Hypertensive DrugsYogeshIJTSRD
Drug repositioning or drug repurposing or drug profiling is the discovery of new applications for approved or failed drug.. Drug repositioning is the development of new approved drug applications. The cost of bringing a medicine to the market is around one million which include clinical and preclinical trials. Repositioning of drugs help in cutting down costs as well as time involve in intial validation and authorization. The procedure involved in Drug repositioning is generally performed during the drug development phase to modify or extend an active molecules distribution line. On a fundamental level, repositioning opportunities exist because drugs perturb multiple biological entities and engage themselves in multiple biological processes. Therefore, a drug can play multiple roles or perform a various mode of actions that are responsible for its pharmacology. Hypertension, is a condition that causes increase in the risk of cardiovascular diseases. In this study an attempt has been made to reposition hypertensive drugs for different diseases by exploring molecular targets of hypertensive drugs. Consider that they often need to be administered for long periods of time, often over whole life time Side effects although present, have been found safe enough to be used for such long durations, hence repurposing these drugs for other diseases may be beneficial with limited side effects. Bhawna Singh | Asmita Das "Exploring Molecular Targets for Repositioning of Hypertensive Drugs" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-3 , April 2021, URL: https://www.ijtsrd.com/papers/ijtsrd39910.pdf Paper URL: https://www.ijtsrd.com/biological-science/bioinformatics/39910/exploring-molecular-targets-for-repositioning-of-hypertensive-drugs/bhawna-singh
Learn how to use Pathway Studio to explore biomarkers and brain regions. With the addition of highly sophisticated visualization tools, users can interactively explore the vast number of connections created to help unravel disease biology. In addition, an innovative new taxonomy based on brain region identifications will be presented. Together, these innovations can be applied to rapidly increase the knowledge of diseases based on published findings.
Cell centered database for immunology and cancer research feb252016Ann-Marie Roche
Determining the cellular mechanisms of diseases is a crucial requirement for understanding the causes and progression of diseases, predicting outcomes, and developing new treatments. Often relevant information, e.g. what cells are involved in a disease or what effects does a drug have on cells, is scattered across many papers and journals, which makes it difficult for researchers to be sure they have a complete picture. Using Elsevier’s automated text mining technology, we have created a new cell-centered database consisting of 850 000 facts captured from more than 24 million PubMed abstracts and 3.5 million full text articles for use in Pathway Studio. This database focused primarily on cellular aspects of immunology and immuno-oncology can be used to summarize and visualize published research, and to analyze experimental data.
Developing Drugs in the New Era of Personalized Medicines by Anita Nelsen - Head of Genomic Medicine, Sr. Director, PAREXEL International and Dr. Sy Pretorius - Sr. Vice President, Chief Scientific Officer, PAREXEL International
Many molecules in nature have geometry, which enables
them to exist as non-superimposable mirror images, or enantiomers.
Modulation of toxicity of such molecules provides
possibility for therapeutics, since they target
multiple points in biochemical pathways. It was hypothesized
that toxicity of a chemical agent, could be counteracted
by a homeopathic preparation of the enantiomer of
the chemical agent
BioVariance - Pediatric Pharmacogenomics in Drug DiscoveryJosef Scheiber
This slideset gives an overview of pharmacogenomic and pediatric dosing knowledge and various influence factors. Finally it shows an example on how to use this kind of Data within predictive approaches.
Establishing other new medical usages for already known drugs, including approved drugs.
Drug repurposing lies in repurposing an active pharmaceutical ingredient for a new indication that is already on the market.
Drug repurposing is a promising approach and mainly applied for the treatment of both common and rare genetic diseases, and it also offers significant benefits to the pharmaceutical industries.
"At its simplest, drug repurposing is taking an existing drug and seeing whether it can be used as an effective treatment for another condition.“
“Repurposing generally refers to studying drugs that are already approved to treat one disease or condition to see if they are safe and effective for treating other diseases”.
The slides from the keynote given by Dr. Dan Malone RPh, PhD at the First International Drug-Drug Interaction Knowledge Representation Workshop on October 6th 2014 (http://icbo14.com/sessions/drug-drug-interaction-knowledge-representation-workshop/). Posted with his permission.
Piloting a Comprehensive Knowledge Base for Pharmacovigilance Using Standardi...Richard Boyce, PhD
A presentation of a new adverse drug event evidence base (Laertes - http://goo.gl/nZSqVw) within a standard framework for clinical research (OHDSI - www.ohdsi.org) made at the American Medical Informatics Association Joint Summits on Translational Research on 3/26/2015
This document presents an overview of the AI applications in life sciences. The presentation highlights various steps in drug development and AI applications. Also, discusses Alzheimer’s disease and obstacles to develop drugs. Finally, presents details of AI in target identification for AD.
This disclaimer informs readers know that the views, thoughts, and opinions expressed in the presentation belong solely to the author, and not to the author’s employer, organization, committee or other group or individual.
Clustering the royal society of chemistry chemical repository to enable enhan...Valery Tkachenko
The Royal Society of Chemistry has hosted the ChemSpider database and associated platforms for over five years. Technologies made significant progress over that period but, more importantly, the community needs in terms of the variety of data types as well as search performance have increased. The preprocessing of chemicals for improved similarity searching and compound database navigation is seen as one crucial component of major development efforts to architect a new data repository. This component is engineered and implemented in collaboration with the group of Professor Oliver Kohlbacher at University of Tübingen. They have developed an approach for clustering large chemical libraries based on a fast, parallel, and purely CPU-based algorithm for 2D binary fingerprint similarity calculation. Using this method, the complete similarity network of our seed set with tens of millions of chemicals has been analyzed at a Tanimoto threshold of 0.6 and all similarity links were fed into our database. The latter is highly beneficial and will allow us to create more complex and enriching visualizations of similar compounds with associated bioactivity data and physicochemical properties for the RSC chemical repository users. This presentation will provide an overview of our experiences in applying clustering to our compound data and how it will be used to enrich data navigation on the RSC data repository.
ACS 248th Paper 136 JSmol/JSpecView Eureka IntegrationStuart Chalk
Integration of the combined JSmol/JSpecView molecular viewer/spectral viewer software in the Eureka Research Workbench. Can display molecular structures, spectra and the linked version where clicking on a peak shows molecular movement (IR).
Building a semantic chemistry platform with the royal society of chemistryValery Tkachenko
We live in an exponentially expanding world of “big data”. Social networks, global portals and other distributed systems have been attempting to deal with the problem for a few years now. Scientific applications are commonly lagging behind the mainstream trends due to the complexity of the scientific domain. The Royal Society of Chemistry is building the Global Chemistry Network connecting a variety of resources both in-house and external, bridging gaps and advancing the chemical sciences. One of the main issues connected to the world of big data is the ease of navigation and comprehensiveness of the search capabilities. This is where the approach of the semantic web meets the world of big data. We will present our approaches in building a global federated chemistry platform connecting multiple domains of chemistry using semantic web technologies.
Supporting the exploding dimensions of the chemical sciences via global netwo...Valery Tkachenko
The Royal Society of Chemistry is building is a comprehensive federated platform for chemical informatics in a Big Research Data world. The resulting platform is a blend of social, informatics and knowledge components which itself produces new dimensions in the chemical sciences to support activities such as Open Innovation and sharing of data. The platform itself would be isolated and insular unless a broad collaboration between societies, industry and universities is created in a federated and open way. In this presentation we will talk about one of these efforts, between RSC and Moscow State University, to facilitate the development, population and use of a global networking platform for the chemical sciences.
Presentation on the Chemical Analysis Metadata Platform (ChAMP) as a new project to characterize and organize metadata about chemical analysis methods. The project will develop an ontology, controlled vocabularies, and design rules
In the last 6 years high-throughput screening has been used to identify FDA approved drugs that are active against multiple targets (also termed promiscuity). We have identified 34 studies that have screened libraries of FDA approved drugs against various whole cell or target assays. Each study has identified one or more compound with a new bioactivity that had not been previously described. Thirteen of these drugs were active against more than one additional disease, thereby suggesting a degree of promiscuity. The 109 molecules identified by screening in vitro were statistically more hydrophobic than orphan designated products with at least one marketing approval for a common disease indication or one marketing approval for a rare disease (FDA rare disease research database). We have created a database of in vitro data on old drugs for new uses that could be applied for repositioning these or other molecules for neglected and rare diseases.
"How Scientific Wellness will Drive The Future of Health" - Nathan Price (Pro...Hyper Wellbeing
"How Scientific Wellness will Drive The Future of Health" - Nathan Price (Professor, Institute of Systems Biology)
Delivered at the inaugural Hyper Wellbeing Summit, 14th November 2016, Mountain View, California.
For more information including details of subsequent events, please visit http://hyperwellbeing.com
The summit was created to foster a community around an emerging industry - Wellness as a Service (WaaS). Consumer technologies, in particular wearables and mobile, are powering a consumer revolution. A revolution to turn health and wellness into platform delivered services. A revolution enabling consumer data-driven disease risk reduction. A revolution extending health care past sick care towards consumer-led lifelong health, wellness and lifestyle optimization.
WaaS newsletter sign-up http://eepurl.com/b71fdr
@hyperwellbeing
5 years of “Rare” Progress Research: Cheryl Rockman-Greenberg, Max Rady College of Medicine, University of Manitoba
Rare Disease Day Conference 2020 March 9-10
Mike generously is sharing this slide set which he presented at the 250th meeting of the ACS 2015 so that others who think they can not afford to run drug discovery can consider this economical distributed, virtual model….and to see CDD Vault in action.
There is an expanding interest in repurposing and repositioning of drugs as well as how in silico methods can assist these endeavors. Recent repurposing project tendering calls by the National Center for Advancing Translational Sciences (US) and the Medical Research Council (UK) have included compound information and pharmacological data. However none of the internal company development code names were assigned to chemical structures in the official documentation. This not only abrogates in silico analysis to support repurposing but consequently necessitates data gathering and curation to assign structures. We describe here the methods results and challenges associated with this, including the fact that ~40-50% of the code names remain completely blinded. In addition we describe the in silico predictions that are enabled once the structures are accessible. Consequently we suggest approaches to encourage earlier release of name to structure mappings into the public domain.
Growing Stronger Research Fund Overview Jan 2012 For DonorsAmer Haider
Website: http://www.growingstroner.org.
Overview of http://www.GrowingStronger.org, a non-profit focused on improving the quality of life of little people through supporting medical research.
Kim Solez Tissue Engineering Pathology Meets Human Cell Atlas a Glimpse into ...Kim Solez ,
Dr. Kim Solez presents "Tissue Engineering Pathology Meets Aviv Regev's Human Cell Atlas: A Glimpse Into the Future of Pathology" on March 8th, 2017 at the University of Alberta in Edmonton, Alberta, Canada Copyright (c) 2017, JustMachines Inc.
Similar to Acs finding promiscuous old drugs for new uses-final (20)
Presentation from AAPS PharmSci360 (October 23, 2023) in which I describe highlights of my Springer/AAPS book Winning Grants (https://link.springer.com/book/10.1007/978-3-031-27516-6) - presenting a 'how to' guide on writing small business grants - e.g. NIH STTR and SBIR grants. Written by someone experienced in winning such grants.
Evaluating Multiple Machine Learning Models for Biodegradation and Aquatic To...Sean Ekins
The presentation was given at SETAC 2022 Nov 16 and describes our work on Evaluating Multiple Machine Learning Models for Biodegradation and Aquatic Toxicity.
We generated many models that are available to license in our MegaTox software. We found that the support vector machines performed the best after assessing many algorithms for both classification and regression models.
The authors of this work are Thomas R Lane, Fabio Urbina and Sean Ekins.
The contact is sean@collaborationspharma.com
A presentation at the Global Genes rare drug development symposium on governm...Sean Ekins
This presentation from June 12 2020 gives a brief overview of my experience of 15 years of applying for government grants to fund small companies. Prior to this I had no experience of applying for such grants. The bottom line for rare disease groups / families is find a scientist that can do this or assist you. please also see www.collaborationspharma.com
Leveraging Science Communication and Social Media to Build Your Brand and Ele...Sean Ekins
Slides from AAPS Careers session by Maren Katherina Preis, Kyle Bagin, Sean Ekins
Provides some clear steps on how you could use social media to help your career.
Oral presentation given in MEDI session at 2017 ACS in DC.
co-authors Kimberley M. Zorn, Mary A. Lingerfelt, Jair L. de Siqueira-Neto, Alex M. Clark, Sean Ekins
describes drug repurposing and machine learning - for more details see www.collaborationspharma.com
Assay Central: A New Approach to Compiling Big Data and Preparing Machine Lea...Sean Ekins
Oral presentation at 2017 ACS in DC - given by Kimberley Zorn
co-authors include Mary A. Lingerfelt, Alex M. Clark, Sean Ekins
for more details see www.collaborationspharma.com
Five Ways to Use Social Media to Raise Awareness for Your Paper or ResearchSean Ekins
Presentation given at the AAPS 2016 conference in Denver. Some of the slides are from AAPS, Some from Kudos and some from Figshare. One slide is from Tony Williams. All slides used with permission.
CDD: Vault, CDD: Vision and CDD: Models software for biologists and chemists ...Sean Ekins
A perspective on 12 yrs of CDD and developing products and collaborations.
A presentation given at the ACS meeting in San Diego - small business section
This presentation summarizes some early efforts on an open drug discovery collaboration between scientists in Brazil and the US. The amazing virus images were created by John Liebler and can be licensed from him http://www.artofthecell.com/animation/will-the-real-zika-virus-please-stand-up
The homology models were created with Swiss Model by Sean Ekins:
Marco Biasini, Stefan Bienert, Andrew Waterhouse, Konstantin Arnold, Gabriel Studer, Tobias Schmidt, Florian Kiefer, Tiziano Gallo Cassarino, Martino Bertoni, Lorenza Bordoli, Torsten Schwede. (2014). SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Research; (1 July 2014) 42 (W1): W252-W258; doi: 10.1093/nar/gku340.
Arnold K., Bordoli L., Kopp J., and Schwede T. (2006). The SWISS-MODEL Workspace: A web-based environment for protein structure homology modelling. Bioinformatics, 22,195-201.
Kiefer F, Arnold K, Künzli M, Bordoli L, Schwede T (2009). The SWISS-MODEL Repository and associated resources. Nucleic Acids Research. 37, D387-D392.
Guex, N., Peitsch, M.C., Schwede, T. (2009). Automated comparative protein structure modeling with SWISS-MODEL and Swiss-PdbViewer: A historical perspective. Electrophoresis, 30(S1), S162-S173.
Ensuring Chemical Structure, Biological Data and Computational Model Quality
A talk given at SLAS 2016 mon Jan 25th in San Diego
covers published work and recent forays with BIA 10-2474
Pros and cons of social networking for scientistsSean Ekins
Over the past 4 years I have been using social networking tools for scientists more inspired by Antony Williams. I realized I am using many tools and there are pros and cons of them. Here is my brief summary.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Colonic and anorectal physiology with surgical implications
Acs finding promiscuous old drugs for new uses-final
1. Finding Promiscuous Old Drugs for New
Uses
Sean Ekins1,2,3,4 and Antony J. Williams5
1Collaborations in Chemistry, Fuquay Varina, NC.
2Collaborative Drug Discovery, Burlingame, CA.
3Department of Pharmacology, University of Medicine & Dentistry of New Jersey-Robert Wood Johnson
Medical School, Piscataway, NJ.
4School of Pharmacy, Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD.
5Royal Society of Chemistry, Wake Forest, NC
2. Why old drugs ?
More cost effective R&D?
Repurposing/ repositioning
-Quicker to bring to market?
Recent focus on neglected
& rare diseases
Over 7000 diseases
affecting less than 200,000
1000’s of diseases with no
treatments
>300 orphan drugs
approved since 1983
Ekins S, Williams AJ, Krasowski MD and Freundlich JS, Drug Disc Today, 16: 298-310, 2011
3. Just some of the many rare disease groups
Abigail Alliance for Better Access to Developmental Drugs MPD Support
Addi & Cassi Fund National Gaucher Foundation
American Behcet's Disease Association National MPS Society
Amschwand Sarcoma Cancer Foundation National Organization Against Rare Cancers
BDSRA (Batten Disease Support and Research Association) National PKU Alliance
Beyond Batten Disease Foundation National Tay-Sachs & Allied Diseases Association
Blake’s Purpose Foundation New Hope Research Foundation
Breakthrough Cancer Coalition NextGEN Policy
Canadian PKU & Allied Disorders Noah's Hope - Batten disease research fund
Center for Orphan Disease Research and Therapy, University of Our Promise to Nicholas Foundation
Pennsylvania Oxalosis and Hyperoxaluria Foundation
Children’s Cardiomyopathy Foundation Partnership for Cures
Cooley's Anemia Foundation Periodic Paralysis Association
Dani’s Foundation RARE Project
Drew’s Hope Research Foundation Ryan Foundation for MPS Children
EveryLife Foundation for Rare Diseases Sanfilippo Foundation for Children
GIST Cancer Awareness Foundation Sarcoma Foundation of America
Hannah's Hope Fund Solving Kids' Cancer
Hope4Bridget Foundation Taylor's Tale: Fighting Batten Disease
Hypertrophic Cardiomyopathy Association - HCMA Team Sanfilippo Foundation
I Have IIH The Alliance Against Alveolar Soft Part Sarcoma
ISRMD (International Society for Mannosidosis and Related Diseases) The Life Raft Group
Jacob’s Cure The NOMID Alliance
Jain Foundation The Transverse Myelitis Association
Jonah's Just Begun-Foundation to Cure Sanfilippo Inc. The XLH Network, Inc.
Kids V Cancer United Pompe Foundation
Kurt+Peter Foundation
LGMD2I Research Fund
Lymphangiomatosis & Gorham's Disease Alliance
MAGIC Foundation
Manton Center for Orphan Disease Research
Many of these groups are
MarbleRoad
Mary Payton's Miracle Foundation doing R&D on a shoestring
Midwest Asian Health Association (MAHA)
how can we help?
4. One example of why Pharmaceutical R&D needs disrupting
Jonah has Sanfilippo Syndrome – Mucopolysaccharidosis type III – cannot degrade heparan
sulfate - Neurodegeneration
Jonah’s mum, Jill Wood started a foundation, raises money, awareness, funds ground breaking
research happening globally. Willing to sell her house to fund research to save Jonah.
She is in a race against time – what can we do to translate ideas from bench to patient faster?
How do we get more ideas tested, can we focus on approved drugs?
How can we help parents and families ?
5. Availability of libraries of FDA drugs
Johns Hopkins Clinical Compound library- made compounds available at cost
6. Finding Promiscuous Old Drugs for New Uses
In late 2010..searched the literature
Many groups in vitro HTS
Libraries of FDA approved drugs against various whole cell or target assays
Research published in the prior six years - 34 studies -.
1 or more compounds with a suggested new bioactivity
13 drugs were active against more than one additional disease in vitro
Perhaps screen these first?
Ekins and Williams, Pharm Res 28(8):1785-91, 2011
7. Finding Promiscuous Old Drugs for New Uses
Multiple tricyclics
Ekins and Williams, Pharm Res 28(8):1785-91, 2011
8. Finding Promiscuous Old Drugs for New Uses
Amitriptyline and clomipramine = suppress glial fibrially acidic protein
Cho et al., Human Mol Genet (2010) 19: 3169-78
Amitriptyline and clomipramine = mitochondrial permeability transition
Stavrovskaya et al., J Exp Med (2004) 200: 211-22
Pyrvinium Pamoate (antihelmintic) = anti Tuberculosis
Lougheed et al., Tuberculosis (2009) 89: 364-70
Pyrvinium Pamoate (antihelmintic) = anti Antiprotozoal C. parvum
Downey et al., Antimicrob Agents Chemother (2008) 52: 3106-12
Pyrvinium Pamoate (antihelmintic) = anti Antiprotozoal T. Brucei
Mackey et al., Chem Biol Drug Des (2006) 355-63
Ekins and Williams, Pharm Res 28(8):1785-91, 2011
9. Analysis of datasets
Dataset ALogP Molecular Number Number Number Number of Number Molecular
Weight of of Rings of Hydrogen of Polar
Rotatable Aromati bond Hydrogen Surface Area
Bonds c Rings Acceptors bond
Donors
Compounds 3.1 ± 428.4 ± 202.8 5.4 ± 3.8 3.8 ± 1.9 2.0 ± 1.4 5.6 ± 4.2 2.0 ± 1.9 89.6 ± 69.3
identified in vitro with 2.6
new activities (N =
109) *
Compounds 3.6 ± 442.8 ± 150.0 5.1 ± 3.1 4.2 ± 1.5 1.8 ± 1.2 5.5 ± 4.6 2.2 ± 3.3 79.5 ± 78.8
identified in vitro with 2.7
multiple new
activities (N = 13)
•Promiscuous repurposed compounds are more hydrophobic,
•Differences not significant
Ekins and Williams, Pharm Res 28(8):1785-91, 2011
10. Finding Promiscuous Old Drugs for New Uses
109 molecules were identified by screening in vitro
Promiscuous compounds do not appear different to whole dataset
Molecules are close to natural product lead like (MW<460, LogP <4.2)
Rosen et al., J Med Chem (2009) 52: 1953-62
1193 Oral drugs mean MW 343.7 CLOGP 2.3
Vieth et al., J Med Chem (2004) 47: 224-32
Others have shown GPCR promiscuous cpds vs selective have higher MW and
clogP
Azzaoui et al., ChemMedComm (2007) 2: 874-80
Our promiscuous cpds had carbon skeletons identified as promiscuous
Hu and baorath, Chem Inf Model (2010) 50: 2112-8
11. FDA Rare Disease Research Database
• The FDA resource, the rare disease research database (RDRD),
(http://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/Howt
oapplyforOrphanProductDesignation/ucm216147.htm)
• Lists Orphan-designated products with at least one marketing approval for a
common disease indication, for a rare disease indication, or for both common and
rare disease indications.
• In the last category there are less than 50 molecules (including large
biopharmaceutical drugs).
• These tables do not capture the high throughput screening (HTS) data generated to
date
•FDA databases for rare disease research are XL files!!
13. Analysis of datasets
Dataset ALogP Molecular Number Number Number Number of Number Molecular
Weight of of Rings of Hydrogen of Polar
Rotatable Aromati bond Hydrogen Surface Area
Bonds c Rings Acceptors bond
Donors
Orphan designated 1.4 ± 353.2 ± 218.8 5.3 ± 6.4 2.8 ± 1.7 1.2 ± 1.3 5.3 ± 6.0 2.5 ± 3.0 99.2 ± 110.7
products with at 3.0 b a a b
least one marketing
approval for a
common disease
indication (N = 79) #
Orphan designated 0.9 ± 344.4 ± 233.5 5.3 ± 5.3 2.4 ± 1.9 1.3 ± 1.4 6.2 ± 4.2 2.7 ± 2.8 114.2 ± 85.3
products with at 3.3 b a b a
least one marketing
approval for a rare
disease indication (N
= 52) #
orphan repurposed hits are less hydrophobic, smaller MW than in vitro screening cpds
Molecules close to lead-like and closer to oral drugs
Ekins and Williams, Pharm Res 28(8):1785-91, 2011
14. Dataset Intersection
Orphan +
Common Orphan +
Use 0 Rare use
0
3 5
In vitro hits
Do these represent frequent
actives or promiscuous
compounds?
15. Finding Promiscuous Old Drugs for New Uses
In vitro screening compounds repurposed –
Statistically more hydrophobic (log P) and higher MWT than orphan-
designated products with at least one marketing approval for a common
disease indication or one marketing approval for a rare disease from the
FDA’s rare disease research database.
Created multiple structure searchable databases in CDD
Data for repurposing in publications is increasing but who is tracking it?
Limited follow up of compounds from in vitro to in vivo..
Will any of these compounds from in vitro be approved?
Then the NPC browser was released early 2011
16. Government Databases Should Come With a Health Warning
Openness Can Bring Serious Quality Issues
Database released and within days 100’s of errors found in structures
Science Translational Medicine 2011 NPC Browser http://tripod.nih.gov/npc/
Science Translational Medicine 2011
Williams and Ekins,
DDT, 16: 747-750 (2011)
17. Data Errors in the NPC Browser: Analysis of Steroids
Substructure # of # of No Incomplete Complete but
Hits Correct stereochemistry Stereochemistry incorrect
Hits stereochemistry
Gonane 34 5 8 21 0
Gon-4-ene 55 12 3 33 7
Gon-1,4-diene 60 17 10 23 10
18. Why drug structure quality is important?
More groups doing in silico repositioning
Target-based or ligand-based
Network and systems biology
They are all integrating or using sets of FDA drugs..if the
structures are incorrect predictions will be too..
What is need is a definitive set of FDA approved drugs
with correct structures and tools for in silico screening
Also linkage between in vitro data & clinical data
19. Repurpose FDA drugs in silico
Key databases of
structures and 2D Similarity search with “hit”
bioactivity data FDA drugs from screening
database
Export database and Suggest
use for 3D searching approved
with a pharmacophore drugs for testing
or other model - may also
indicate other
uses if it is
present in more
than one
database
Suggest in silico hits
for in vitro screening
Ekins S, Williams AJ, Krasowski MD and Freundlich JS, Drug Disc Today, 16: 298-310, 2011
20. An example for TB and more
Bayesian models for TB whole cell data
200,000 single point
% hits identified
Over 2000 dose response
Used publication that identified compounds with whole
cell activity FDA drugs 2108 molecules (21 actives)
Lougheed et al., Tuberculosis (2009) 89:364-70
Numerous examples of pharmacophores screening drugs
and finding transporter inhibitors, PXR agonists, PXR
antagonists etc..
Ekins et al., Mol Pharmacol, 74(3):662-72 , (2008)
Could use large datasets for other diseases, targets to
build models search FDA drugs….and repurpose
Ekins et al., Mol BioSyst, 6: 840-851, 2010 Ekins and Freundlich, Pharm Res, 28, 1859-1869, 2011.
21. Need to learn from neglected disease research
Do we really need to screen
massive libraries of compounds as
we have for TB and malaria?
And groups are screening
compounds already screened by
others!
Ekins S and Williams AJ, MedChemComm,
http://www.slideshare.net/ekinssean
1: 325-330, 2010.
22. Rare diseases: Searching for Potential Chaperones
for Sanfilippo Syndrome
Pshezhetsky et al showed Glucosamine rescues
HGSNAT mutants
Feldhammer et al., Hum Mutat. 2009 30:918-25
Glucosamine used to create a 3D common features
pharmacophore using Discovery Studio.
The pharmacophore + ligand van der Waals shape
was used to search multiple 3D databases
FDA drugs, natural products, orphan drugs, KEGG,
CSF metabolome etc.
The pharmacophore consists of a positive ionizable
(red) and 3 hydrogen bond donor groups (purple).
Selected hits for experimental testing
Collaboration ongoing!
e.g. Isofagomine maps pharmacophore
23. A path forwards for rare diseases using old drugs?
We propose generalizable methods utilizing transcriptomic, system-wide chemical biology
datasets combined with chemical informatics and, where possible, repurposing of FDA
approved drugs for pre-clinical orphan disease therapies.
A generalizable pre-clinical research approach for orphan disease
therapy Chandree L. Beaulieu et al., submitted 2012
24. Crowdsourcing Project “Off the Shelf R&D”
How can we access more chemistry space?
All pharmas have assets on shelf that reached clinic
“Off the Shelf R&D”
Get the crowd to help in repurposing / repositioning
these assets
How can software help?
- Create communities to test
- Provide informatics tools that are accessible to the
crowd - enlarge user base
- Data storage on cloud – integration with public data
- Crowd becomes virtual pharma-CROs and the
“customer” for enabling services
25. Finding Promiscuous Old Drugs for New Uses
Update 2011-2012
everolimus
5-fluorouracil
ceftriaxone
Could In silico / in vitro repositioning find leads-drugs quicker?
26. Acknowledgments
Jill Wood
Joel Freundlich (UMDNJ),
Matthew D. Krasowski (University of Iowa)
Chris Lipinski
David Sullivan (Johns Hopkins)
Accelrys
CDD – Barry Bunin
Everyone that has shared data in CDD..
Email: ekinssean@yahoo.com
Slideshare: http://www.slideshare.net/ekinssean
Twitter: collabchem
Blog: http://www.collabchem.com/
Website: http://www.collaborations.com/CHEMISTRY.HTM