Skip to main content

Seminar: Discovery of Viagra/Revatio (aka sildenafil aka UK-92480)






A reminder of an on campus, open, seminar from Andy Bell (now at Imperial College), detailing the discovery and development of UK-92,480 (also known as sildenafil and even better known as V1agra and R3vat10). Andy was one of the medicinal chemists and inventors on the PDE-5 inhibitor programme at Pfizer, and the story covers many aspects of drug discovery including, of course, the discovery of the side effect, and also one where the pharmacology led to many new molecular insights into NO signalling and PDE biology.

There are many myths about the discovery of V1agra, so this is a rare opportunity to hear the exciting story first-hand.


Here's Andy's abstract....


"Viagraâ„¢ (sildenafil) is a unique example of a chemical tool being used to
discover the linkage between a biological mechanism and a disease through
clinical trials. The presentation will describe the discovery of sildenafil
and its use in defining the role of cGMP phosphodiesterases (particularly
PDE5) in human diseases such as Male Erectile Dysfunction (MED) and Pulmonary
Arterial Hypertension (PAH). These clinical studies, combined with the
discovery of additional PDE isoforms, were used to define a desirable profile
for subsequent 2nd generation PDE5 inhibitors. The impact of structural
biology and high throughput screening on the discovery of further clinical
candidates will also be discussed."



The seminar  is on Tuesday July 17th 2012 at 2pm in room M203 (room change alert for those who put it in their diary earlier) - you will need to mail me in order to get registered with campus security if you don't work on campus. If you do, you can just turn up.


Andy will also be giving a more detailed technical seminar on screening file analysis, diversity, chemical space, etc - again, let me know if you are interested in attending this too......

Comments

Popular posts from this blog

ChEMBL 34 is out!

We are delighted to announce the release of ChEMBL 34, which includes a full update to drug and clinical candidate drug data. This version of the database, prepared on 28/03/2024 contains:         2,431,025 compounds (of which 2,409,270 have mol files)         3,106,257 compound records (non-unique compounds)         20,772,701 activities         1,644,390 assays         15,598 targets         89,892 documents Data can be downloaded from the ChEMBL FTP site:  https://ftp.ebi.ac.uk/pub/databases/chembl/ChEMBLdb/releases/chembl_34/ Please see ChEMBL_34 release notes for full details of all changes in this release:  https://ftp.ebi.ac.uk/pub/databases/chembl/ChEMBLdb/releases/chembl_34/chembl_34_release_notes.txt New Data Sources European Medicines Agency (src_id = 66): European Medicines Agency's data correspond to EMA drugs prior to 20 January 2023 (excluding ...

SureChEMBL gets a facelift

    Dear SureChEMBL users, Over the past year, we’ve introduced several updates to the SureChEMBL platform, focusing on improving functionality while maintaining a clean and intuitive design. Even small changes can have a big impact on your experience, and our goal remains the same: to provide high-quality patent annotation with a simple, effective way to find the data you need. What’s Changed? After careful consideration, we’ve redesigned the landing page to make your navigation smoother and more intuitive. From top to bottom: - Announcements Section: Stay up to date with the latest news and updates directly from this blog. Never miss any update! - Enhanced Search Bar: The main search bar is still your go-to for text searches, still with three pre-filter radio buttons to quickly narrow your results without hassle. - Improved Query Assistant: Our query assistant has been redesigned and upgraded to help you craft more precise queries. It now includes five operator options: E...

Here's a nice Christmas gift - ChEMBL 35 is out!

Use your well-deserved Christmas holidays to spend time with your loved ones and explore the new release of ChEMBL 35!            This fresh release comes with a wealth of new data sets and some new data sources as well. Examples include a total of 14 datasets deposited by by the ASAP ( AI-driven Structure-enabled Antiviral Platform) project, a new NTD data se t by Aberystwyth University on anti-schistosome activity, nine new chemical probe data sets, and seven new data sets for the Chemogenomic library of the EUbOPEN project. We also inlcuded a few new fields that do impr ove the provenance and FAIRness of the data we host in ChEMBL:  1) A CONTACT field has been added to the DOCs table which should contain a contact profile of someone willing to be contacted about details of the dataset (ideally an ORCID ID; up to 3 contacts can be provided). 2) In an effort to provide more detailed information about the source of a deposited dat...

Improvements in SureChEMBL's chemistry search and adoption of RDKit

    Dear SureChEMBL users, If you frequently rely on our "chemistry search" feature, today brings great news! We’ve recently implemented a major update that makes your search experience faster than ever. What's New? Last week, we upgraded our structure search engine by aligning it with the core code base used in ChEMBL . This update allows SureChEMBL to leverage our FPSim2 Python package , returning results in approximately one second. The similarity search relies on 256-bit RDKit -calculated ECFP4 fingerprints, and a single instance requires approximately 1 GB of RAM to run. SureChEMBL’s FPSim2 file is not currently available for download, but we are considering generating it periodicaly and have created it once for you to try in Google Colab ! For substructure searches, we now also use an RDKit -based solution via SubstructLibrary , which returns results several times faster than our previous implementation. Additionally, structure search results are now sorted by...

A python client for accessing ChEMBL web services

Motivation The CheMBL Web Services provide simple reliable programmatic access to the data stored in ChEMBL database. RESTful API approaches are quite easy to master in most languages but still require writing a few lines of code. Additionally, it can be a challenging task to write a nontrivial application using REST without any examples. These factors were the motivation for us to write a small client library for accessing web services from Python. Why Python? We choose this language because Python has become extremely popular (and still growing in use) in scientific applications; there are several Open Source chemical toolkits available in this language, and so the wealth of ChEMBL resources and functionality of those toolkits can be easily combined. Moreover, Python is a very web-friendly language and we wanted to show how easy complex resource acquisition can be expressed in Python. Reinventing the wheel? There are already some libraries providing access to ChEM...