I've tried to support research in the Neglected Tropical Disease area in several ways, I organised a session at the 19th Cambridge MedChem Meeting in 2017 and arranged for the session to be recorded and is now available online and has been watched nearly 300 times.
This is a recording of the Neglected and Tropical Diseases Session at the 19th Cambridge MedChem Meeting, 11-13 September 2017. The speakers are Kelly Chibale (Univ of Capetown), Christoph Boss (Actelion), Rob Young (GlaxoSmithKline), Jonathan Large (LifeArc) and Charles Mowbray (DNDI).
So I was delighted to hear that IUPHAR/BPS Guide to pharmacology database have been funded by MMV to add details of antimalarials to their database.
This link http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=970 gives details of antimalarial targets, including gene name, synonyms and Uniprot ID.
This link http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=999 gives details of antimalarial ligands, including mode of action and properties. For example artemisinin.
I'd urge you have a look and I'm sure they would be happy to hear any suggestions.
I've spent a little time updating the Drug Discovery Resources Section of the website. In particular:
- CYP interactions now includes details of published crystal structures and more information on known inhibitors
- I've added page on CYP1A2 from ChEMBL data and updated the CYP2D6 and CYP3A4 pages
- Updated the page on Aldehyde Oxidase
- Added new examples on the bioisosteres page
- Updated the Published Fragments section, including adding the overlay of all examples of Kinase fragment hits from the PDB.
- Added new examples to the Chemical Probes page
- Included more examples of halogen bonding to the Molecular Interactions page
20th SCI/RSC Medicinal Chemistry Symposium on 8 - 11 September 2019 at Churchill College, Cambridge.
Abstract deadline: Friday 9th November 2018
The organising committee wishes to solicit late-breaking, high impact medicinal chemistry talks to finalise the scientific programme. Potential contributions should be communicated to the secretariat at firstname.lastname@example.org by Friday 9th November 2018. A number of conference places will be reserved for poster presenters and contributions are invited from the whole field of medicinal chemistry. Those presenting a poster may also elect to advertise their poster via oral presentation of a single slide 'flash' poster. Detailed procedures and submission deadlines for poster abstracts will be provided in the second announcement.
Cyclophilin D (CYP D), is a member of a family of highly homologous peptidylprolyl cis-trans isomerases (PPIases) that interconvert the cis and trans isomers of peptide bonds with the amino acid proline. Proteins with prolyl isomerase activity include cyclophilins, FKBPs, and parvulin. Inhibitors of Cyclophilin D have been postulated as potential drugs for a variety of therapeutic targets including anti-viral activity DOI, neurodegenration DOI, Cancer DOI etc.
Until recently work in this area suffered from the lack of high quality, selective inhibitors, the best studied being the immunosuppressants Cyclosporin and Sanglifehrin A.
At the recent Macrocycles 2018 meeting Vicky Steadman described the identification and optimisation of potent and orally available selective Cyclophilin inhibitors, more details have just been published J Med Chem paper DOI.
Let's hope with potent, cell penetrant and orally available tools in hand we can sort out the biology and bring forward a new class of therapeutic agents.
This looks a very interesting resource described in a recent publication. The ReFRAME library as a comprehensive drug repurposing library and its application to the treatment of cryptosporidiosis DOI.
The ReFRAME collection of 12,000 compounds is a best-in-class drug repurposing library containing nearly all small molecules that have reached clinical development or undergone significant preclinical profiling. The purpose of such a screening collection is to enable rapid testing of compounds with demonstrated safety profiles in new indications, such as neglected or rare diseases, where there is less commercial motivation for expensive research and development.
To date, 12,000 compounds (80% of compounds identified from data mining) have been purchased or synthesized and subsequently plated for screening. In addition, an open-access data portal (https://reframedb.org) has been developed to share ReFRAME screen hits to encourage additional follow-up and maximize the impact of the ReFRAME screening collection.
The website can be searched by structure or text string.
For Example searching for Malaria highlights a number of known therapeutic agents.
This looks like it will be an invaluable resource.
As mentioned on the Target Validation page, Open Targets is a public-private partnership that uses human genetics and genomics data for systematic drug target identification and prioritisation. The current focus is on oncology, immunology and neurodegeneration. An extension to this will be launched on 18 October 2018.
Open Targets Genetics is a new portal developed by Open Targets, an innovative partnership that brings together expertise from six complementary institutions to systematically identify and prioritise targets from which safe and effective medicines can be developed. The Portal offers three unique features to help you discover new associations between genes, variants, and traits, Gene2Variant analysis pipeline, Fine mapping/ credible set analysis, UK Biobank + GWAS Catalog integration.
In an excellent publication "Where do recent small molecule clinical development candidates come from?" DOI, the authors give a detailed description on the development of clinical candidates from the initial hit. They also define the changes in physicochemical properties.
An analysis of physicochemical properties on the hit-to-clinical pairs shows an average increase in molecular weight (ΔMW = +85) but no change in lipophilicity (ΔclogP = −0.2), although exceptions are noted. The majority (>50%) of clinical candidates were found to be structurally very different from their starting point and were more complex.
I thought it might be interesting to look at the calculated properties of the 66 clinical candidates. Interestingly many have molecular weights > 500 and only around 30% contain an ionisable group. All structures contain an aromatic ring and 48 molecules contain 3 or more aromatic rings.
In case anyone was wondering the high molecular weight compounds are not peptides or macrocycles.
The Molecular Interactions page has been updated to include a section on anion-aryl interactions.
Just announced. Open Targets Platform release - 18.08.
In this release there is now data on:
- 21,149 targets
- 10,101 diseases
- 6.5 million pieces of evidence
- 2.9 million associations between targets and diseases
The Open Targets Platform is a comprehensive and robust data integration for access to and visualisation of potential drug targets associated with disease. It brings together multiple data types and aims to assist users to identify and prioritise targets for further investigation. A drug target can be a protein, protein complex or RNA molecule and it’s displayed by its gene name from the Human Gene Nomenclature Committee, HGNC. We integrate all the evidence to the target using Ensembl stable IDs and describe relationships between diseases by mapping them to Experimental Factor Ontology (EFO) terms. The Platform supports workflows starting from a target or disease, and shows the available evidence for target – disease associations. Target and Disease profile pages showing specific information for both target (e.g baseline expression) and disease (e.g. Disease Classification) are also available
A couple of people have asked me how to access the category tags that are attached to news items, the short answer is not easily so I've created a new tab at the top of the page that gives you direct access.
Click on the link and you will get an alphabetical listing of all categories with appropriate links.
It may take a day or so for the new menu bar to appear on all pages.