An overview of the issues and approaches in selecting the best targets for drug discovery and validating them. Given at the Drug Discovery Forum held at the Royal Society, London and organised by the Academy of Medical Sciences
ACRI is a leading clinical research training institute in Bangalore.
ACRI creates a value add for every degree. Our PGDCRCDM course is approved by the Mysore University. Graduates and Post Graduates and even PhDs have trained with us and got enviable positions in the Clinical Research Industry. ACRI supplements University training with Industry based training, coupled with hands-on internships and projects based on real case studies. The ACRI brand gives the individual the confidence and expertise to join the ever-growing workforce both in the country and abroad.
Drug discovery is an inventive process of identifying a compound or new medication based on knowledge of biological target, therapeutically useful in treating and curing a disease.
The process of drug discovery involves the identification of candidates,synthesis, characterization,screening,assays for therapeutic efficacy.
Once a compound has shown its value in these tests, it will begin the process of drug development prior to clinical trials.
ACRI is a leading clinical research training institute in Bangalore.
ACRI creates a value add for every degree. Our PGDCRCDM course is approved by the Mysore University. Graduates and Post Graduates and even PhDs have trained with us and got enviable positions in the Clinical Research Industry. ACRI supplements University training with Industry based training, coupled with hands-on internships and projects based on real case studies. The ACRI brand gives the individual the confidence and expertise to join the ever-growing workforce both in the country and abroad.
Drug discovery is an inventive process of identifying a compound or new medication based on knowledge of biological target, therapeutically useful in treating and curing a disease.
The process of drug discovery involves the identification of candidates,synthesis, characterization,screening,assays for therapeutic efficacy.
Once a compound has shown its value in these tests, it will begin the process of drug development prior to clinical trials.
Tools for target identification and validationDr. sreeremya S
Microarrays
Target identification seeks to identify new targets, normally
proteins (or DNA/RNA), whose modulation might
inhibit or reverse disease progression. Current technologies
enable researchers to attempt to correlate changes in
gene (genomics) and protein (proteomics) expression
with human disease, in the hope of finding new targets.
Microarrays are a well-utilized tool in both academic and
industrial research laboratories. They can be used to
assess gene and protein expression (via nucleic acid or
protein microarrays) to identify novel targets, and can also
be used to validate the found targets at the tissue or cell
scale (via tissue or cell microarrays
Part of the MaRS Best Practices Series - Pre-Clinical development workshop
http://www.marsdd.com/bestpractices
Speaker: Jack Jiang, VP Medicinal and Analytical Chemistry, Ricerca BioSciences
Topic explained as a M.Sc. Microbiology Student point of you. It contains general Properties of drug, its discovery process and Rational Drug Design Process using Bioinformatic Tools.
The basic aspects of drug discovery starts from target discovery and validation further going to lead identification and optimization. In this particular slide discussion is regarding the target discovery and the tools that have been utilized in this process.
INTRODUCTION
A PERFECT THERAPEUTIC DRUG
DRUG DISCOVERY- HISTORY
MODERN DRUG DISCOVERY
BIOINFORATICS IN DRUG DISCOVERY
DRUG DISCOVERY BASED ON BIOINFORMATIC TOOLS
BIOINFORMATICS IN COMPUTER-AIDED DRUG DISCOVERY
ECONOMICS OF DRUG DISCOVERY
CONCLUSION
REFERENCES
Molecular target and development modelsAmjad Afridi
Molecular targets are cellular or tissue structures that are intended to be visualized by means of molecular imaging.
Different biological structures can potentially serve as imaging targets.
These Targets ranging from gene mutations, mRNA levels, protein levels, DNA, RNA and enzyme activities.
Drug Discovery: Target Identification and Validation Lindsay Rosenwald
For many years, pharmaceutical research companies have developed new drugs using a standard drug discovery process. The process usually begins with extensive medical research about a particular disease, which provides researchers with a better understanding of the disease and how it affects the body. The next step of the drug discovery process typically involves target identification and target validation.
Tools for target identification and validationDr. sreeremya S
Microarrays
Target identification seeks to identify new targets, normally
proteins (or DNA/RNA), whose modulation might
inhibit or reverse disease progression. Current technologies
enable researchers to attempt to correlate changes in
gene (genomics) and protein (proteomics) expression
with human disease, in the hope of finding new targets.
Microarrays are a well-utilized tool in both academic and
industrial research laboratories. They can be used to
assess gene and protein expression (via nucleic acid or
protein microarrays) to identify novel targets, and can also
be used to validate the found targets at the tissue or cell
scale (via tissue or cell microarrays
Part of the MaRS Best Practices Series - Pre-Clinical development workshop
http://www.marsdd.com/bestpractices
Speaker: Jack Jiang, VP Medicinal and Analytical Chemistry, Ricerca BioSciences
Topic explained as a M.Sc. Microbiology Student point of you. It contains general Properties of drug, its discovery process and Rational Drug Design Process using Bioinformatic Tools.
The basic aspects of drug discovery starts from target discovery and validation further going to lead identification and optimization. In this particular slide discussion is regarding the target discovery and the tools that have been utilized in this process.
INTRODUCTION
A PERFECT THERAPEUTIC DRUG
DRUG DISCOVERY- HISTORY
MODERN DRUG DISCOVERY
BIOINFORATICS IN DRUG DISCOVERY
DRUG DISCOVERY BASED ON BIOINFORMATIC TOOLS
BIOINFORMATICS IN COMPUTER-AIDED DRUG DISCOVERY
ECONOMICS OF DRUG DISCOVERY
CONCLUSION
REFERENCES
Molecular target and development modelsAmjad Afridi
Molecular targets are cellular or tissue structures that are intended to be visualized by means of molecular imaging.
Different biological structures can potentially serve as imaging targets.
These Targets ranging from gene mutations, mRNA levels, protein levels, DNA, RNA and enzyme activities.
Drug Discovery: Target Identification and Validation Lindsay Rosenwald
For many years, pharmaceutical research companies have developed new drugs using a standard drug discovery process. The process usually begins with extensive medical research about a particular disease, which provides researchers with a better understanding of the disease and how it affects the body. The next step of the drug discovery process typically involves target identification and target validation.
A presentation outlining the various processes a chemical compound undergoes (thorough & rigorous screening procedures) before it is finally introduced into the drug market
Wendy Cornell, Director, Chemistry Modeling and Informatics at Merck, moderates an expert
panel discussion on targets in drug discovery. The panelists are: Jamie Baumgartner, Ph.D.,
Senior Director of in vitro Pharmacology at MDS Pharma Services, Brian Lightbody, Vice President
of Business Development of Small Molecule Drug Discovery for MicroCal Products Group,
GE Healthcare, and Patrick Zarrinkar, Vice President of Technology Development at Ambit BioSciences
Integrating Disruptive Technologies Into Translational Research Hinxton Hal...Mike Romanos
Introduction to a session with the same title. Addresses the challenges in drug discovery and how disruptive technologies can help. Focusses on use of RNAi and stem cells in translational studies
Answer four fundamental questions on how to develop the most innovative cancer immunotherapy treatments, starting with screening for lead molecules and ending with evaluation of combination therapies.
2015 11-26 ODDP2015 Course Oncology Drug Development, Amsterdam, Alain van GoolAlain van Gool
Tutorial lecture explaining real case stories of oncology drug development, passing on lessons learned from my pharma days to an audience of research professionals.
Recurrent/Metastatic HNSCC: Harnessing Immunotherapy in Comprehensive Carei3 Health
i3 Health is pleased to make this slide deck from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck, presented by Glenn J. Hanna, MD, Director, Center for Cancer Therapeutic Innovation (Early Drug Development Program)
Medical Oncologist, Center for Head & Neck Oncology
Dana-Farber Cancer Institute, and Deborah Wong, MD, PhD, Associate Clinical Professor of Medicine, Division of Hematology-Oncology, UCLA Medical Center, was presented at a live educational event at the 2024 Multidisciplinary Head and Neck Cancers Symposium. It will provide expert perspectives on harnessing immunotherapy in recurrent/metastatic HNSCC to provide comprehensive care.
2014 11-27 ODDP 2014 course, Amsterdam, Alain van GoolAlain van Gool
Presentation as part of a comprehensive oncology drug development course, to discuss a pharmaceutical approach to identify, validate and develop biomarkers for personalized medicine for melanoma.
Personalized medicine involves the prescription of specific therapeutics best suited for an individual based on their genetic or proteomic profile. This talk discusses current approaches in drug discovery/development, the role of genetics in drug metabolism, and lawful/ethical issues surrounding the deployment of new health technology. I highlight some bioinformatic roles in the drug discovery process, and discuss the use of semantic web technologies for data integration and knowledge discovery..
Personalized medicine involves the prescription of specific therapeutics best suited for an individual based on their genetic or proteomic profile. This talk discusses current approaches in drug discovery/development, the role of genetics in drug metabolism, and lawful/ethical issues surrounding the deployment of new health technology.
LF Energy Webinar: Electrical Grid Modelling and Simulation Through PowSyBl -...DanBrown980551
Do you want to learn how to model and simulate an electrical network from scratch in under an hour?
Then welcome to this PowSyBl workshop, hosted by Rte, the French Transmission System Operator (TSO)!
During the webinar, you will discover the PowSyBl ecosystem as well as handle and study an electrical network through an interactive Python notebook.
PowSyBl is an open source project hosted by LF Energy, which offers a comprehensive set of features for electrical grid modelling and simulation. Among other advanced features, PowSyBl provides:
- A fully editable and extendable library for grid component modelling;
- Visualization tools to display your network;
- Grid simulation tools, such as power flows, security analyses (with or without remedial actions) and sensitivity analyses;
The framework is mostly written in Java, with a Python binding so that Python developers can access PowSyBl functionalities as well.
What you will learn during the webinar:
- For beginners: discover PowSyBl's functionalities through a quick general presentation and the notebook, without needing any expert coding skills;
- For advanced developers: master the skills to efficiently apply PowSyBl functionalities to your real-world scenarios.
Securing your Kubernetes cluster_ a step-by-step guide to success !KatiaHIMEUR1
Today, after several years of existence, an extremely active community and an ultra-dynamic ecosystem, Kubernetes has established itself as the de facto standard in container orchestration. Thanks to a wide range of managed services, it has never been so easy to set up a ready-to-use Kubernetes cluster.
However, this ease of use means that the subject of security in Kubernetes is often left for later, or even neglected. This exposes companies to significant risks.
In this talk, I'll show you step-by-step how to secure your Kubernetes cluster for greater peace of mind and reliability.
GraphRAG is All You need? LLM & Knowledge GraphGuy Korland
Guy Korland, CEO and Co-founder of FalkorDB, will review two articles on the integration of language models with knowledge graphs.
1. Unifying Large Language Models and Knowledge Graphs: A Roadmap.
https://arxiv.org/abs/2306.08302
2. Microsoft Research's GraphRAG paper and a review paper on various uses of knowledge graphs:
https://www.microsoft.com/en-us/research/blog/graphrag-unlocking-llm-discovery-on-narrative-private-data/
Elevating Tactical DDD Patterns Through Object CalisthenicsDorra BARTAGUIZ
After immersing yourself in the blue book and its red counterpart, attending DDD-focused conferences, and applying tactical patterns, you're left with a crucial question: How do I ensure my design is effective? Tactical patterns within Domain-Driven Design (DDD) serve as guiding principles for creating clear and manageable domain models. However, achieving success with these patterns requires additional guidance. Interestingly, we've observed that a set of constraints initially designed for training purposes remarkably aligns with effective pattern implementation, offering a more ‘mechanical’ approach. Let's explore together how Object Calisthenics can elevate the design of your tactical DDD patterns, offering concrete help for those venturing into DDD for the first time!
Neuro-symbolic is not enough, we need neuro-*semantic*Frank van Harmelen
Neuro-symbolic (NeSy) AI is on the rise. However, simply machine learning on just any symbolic structure is not sufficient to really harvest the gains of NeSy. These will only be gained when the symbolic structures have an actual semantics. I give an operational definition of semantics as “predictable inference”.
All of this illustrated with link prediction over knowledge graphs, but the argument is general.
Connector Corner: Automate dynamic content and events by pushing a buttonDianaGray10
Here is something new! In our next Connector Corner webinar, we will demonstrate how you can use a single workflow to:
Create a campaign using Mailchimp with merge tags/fields
Send an interactive Slack channel message (using buttons)
Have the message received by managers and peers along with a test email for review
But there’s more:
In a second workflow supporting the same use case, you’ll see:
Your campaign sent to target colleagues for approval
If the “Approve” button is clicked, a Jira/Zendesk ticket is created for the marketing design team
But—if the “Reject” button is pushed, colleagues will be alerted via Slack message
Join us to learn more about this new, human-in-the-loop capability, brought to you by Integration Service connectors.
And...
Speakers:
Akshay Agnihotri, Product Manager
Charlie Greenberg, Host
Essentials of Automations: Optimizing FME Workflows with ParametersSafe Software
Are you looking to streamline your workflows and boost your projects’ efficiency? Do you find yourself searching for ways to add flexibility and control over your FME workflows? If so, you’re in the right place.
Join us for an insightful dive into the world of FME parameters, a critical element in optimizing workflow efficiency. This webinar marks the beginning of our three-part “Essentials of Automation” series. This first webinar is designed to equip you with the knowledge and skills to utilize parameters effectively: enhancing the flexibility, maintainability, and user control of your FME projects.
Here’s what you’ll gain:
- Essentials of FME Parameters: Understand the pivotal role of parameters, including Reader/Writer, Transformer, User, and FME Flow categories. Discover how they are the key to unlocking automation and optimization within your workflows.
- Practical Applications in FME Form: Delve into key user parameter types including choice, connections, and file URLs. Allow users to control how a workflow runs, making your workflows more reusable. Learn to import values and deliver the best user experience for your workflows while enhancing accuracy.
- Optimization Strategies in FME Flow: Explore the creation and strategic deployment of parameters in FME Flow, including the use of deployment and geometry parameters, to maximize workflow efficiency.
- Pro Tips for Success: Gain insights on parameterizing connections and leveraging new features like Conditional Visibility for clarity and simplicity.
We’ll wrap up with a glimpse into future webinars, followed by a Q&A session to address your specific questions surrounding this topic.
Don’t miss this opportunity to elevate your FME expertise and drive your projects to new heights of efficiency.
Key Trends Shaping the Future of Infrastructure.pdfCheryl Hung
Keynote at DIGIT West Expo, Glasgow on 29 May 2024.
Cheryl Hung, ochery.com
Sr Director, Infrastructure Ecosystem, Arm.
The key trends across hardware, cloud and open-source; exploring how these areas are likely to mature and develop over the short and long-term, and then considering how organisations can position themselves to adapt and thrive.
Smart TV Buyer Insights Survey 2024 by 91mobiles.pdf91mobiles
91mobiles recently conducted a Smart TV Buyer Insights Survey in which we asked over 3,000 respondents about the TV they own, aspects they look at on a new TV, and their TV buying preferences.
Accelerate your Kubernetes clusters with Varnish CachingThijs Feryn
A presentation about the usage and availability of Varnish on Kubernetes. This talk explores the capabilities of Varnish caching and shows how to use the Varnish Helm chart to deploy it to Kubernetes.
This presentation was delivered at K8SUG Singapore. See https://feryn.eu/presentations/accelerate-your-kubernetes-clusters-with-varnish-caching-k8sug-singapore-28-2024 for more details.
Target Validation Academy Of Medical Sciences 1 Dec 2006
1. Target Validation Academy of Medical Sciences London 1 st Dec 2006 Mike Romanos VP Discovery Technology GlaxoSmithKline R&D Stevenage
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4. Drug Discovery Process and Target Validation Continuum Gene to target Target to Lead Lead to candidate Candidate to FTIH FTIH to PoC PoC to Commit to Phase III Phase III File & Launch Lifecycle mgt Target selection Lead validation Compound on/off target effects Refined validation vs product profile TARGET VALIDATION Translational medicine
5. Essential Tools: Biological Systems Animal models of disease Human tissues Disease-relevant cell models Humans
11. FXR: Master Regulator of Bile Acid Homeostasis cholesterol Liver Intestine blood bile acid bile bile acid RXR FXR bile acid RXR FXR bile acid
12. Efficacy of GW4064 in Cholestasis Model # p<0.05 cw Normal * p<0.05 cw ANIT Bile Acids Bilirubin 0 200 400 600 800 Bile acid (µmol/L) 0 1 2 3 4 5 6 Total bilirubin (mg/dL) * # # Enzyme activity (U/L) 0 500 1000 1500 2000 ALT AST # # * * Liu et al., JCI , 112 , 1678 (2003) Normal ANIT ANIT+GW4064 ANIT+TUDCA
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16. Mouse VR1 Knockout No response to capsaicin – no overt pathology No hyperalgaesia induced by inflammatory insult (but no effect on mechanical hypersensitivity) -8.0 -7.0 -6.0 -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 Capsaicin (KO) Vehicle (KO) Capsaicin (Het) Vehicle (Het) Capsaicin (WT) Vehicle (WT) Mean Maximum Temp Change (Centigrade )
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18. VR1 expression is up-regulated in chronic inflamed rectum A proliferation of VR1 positive nerve terminals is seen in chronic inflamed gut (oesophagus) C22, 1:5000 Human Disease Tissue: VR1 in Visceral Pain rectal mucosa Normal Hyper 0.0 0.1 0.2 0.3 0.4 0.5 0.6 VR1 immunoreactivity % area p = 0.0286 Mann Whitney U
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21. siRNA Target Identification in Inflammatory Diseases Assays selected to reflect key disease mechanisms Mast Cells: IgER mediated histamine release (Rhinitis) Dendritic Cells: CD40 mediated IL-12 release (Asthma) Macrophages: IC mediated TNF release (RA) Epithelial Cells: Oxidative stress mediated cytokine release/apoptosis (COPD) T Cells: CD3/CD28 mediated IL-5 and IL-13 release (Asthma) siRNA
22. siRNA for High Throughput Screen BioFocus Collaboration: Biology-driven Target Discovery
23. Validation of Target A and B in Primary Human CD4+ Cells Using siRNA Target A (TCR response) Target B (antigen response) Profound inhibition of key cytokines in Rheumatoid Arthritis (TNF ) and Asthma (IL13) * Selective inhibition of Asthma ‘pathological’ cytokine production 0 1000 2000 3000 4000 5000 6000 7000 TNFa IL13 pg/ml Control T Target A IL13 Control Target B 0 1000 2000 3000 4000 5000 pg/ml
24. Target Validation in Human Disease Tissue Targeting Allergen Specific T Cell Responses in Asthma Effect of drug on secretion of Cytokines and other Mediators Supernatant allergic asthmatic biopsy material Allergen ± Drug p=0.02 Unchallenged allergen challenged allergen challenged +drug Effect of tool compound to Target A on IL-5 release
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28. Clinical improvement Clinical decline Model-adjusted mean Change from baseline in ADAS-cog by ApoE4 status Pharmacogenetic Stratification Enables Observation of Clinical Efficacy: Roziglitazone in AD
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