Next Online Meeting - 24th May 2016

[mattodd]

The next online strategy meeting will be on May 24th. It’ll be a little different from normal. Mark Gardner, from AMG Consultants, is organizing the latest in his series of Global Health Drug Discovery Webinars to focus on OSM. This is great for a number of reasons - Mark reaches out to people and communities that may lie outside of those we typically reach with OSM meetings, and Mark was involved with Series 4 at Pfizer at the very beginning, before OSM took it on - he’s therefore familiar with the strengths and weaknesses of the compounds as they stand.

Register here - you need to in order to receive the link for the meeting itself. The first flyer is below. The second flyer, giving more information on all the issues, can be downloaded here. Please forward this on to anyone you think might be interested, particularly groups of students interested in, or currently studying, med chem and who might want to get involved with a “real live” medchem project.

Additional files and links to recordings etc (for after this Issue is closed) can be found on the ELN. For example here is the Series 4 SDF.

Outline agenda:

Project background & scientific objectives (5) Overview of project information sources - ie what's where (5) Data sources & summary of analyses (5-10) SAR overview, questions for the audience (20) Discussion (10-15) Final guidance on what's required from the audience & how to submit your suggestions & what happens next (5)

Discussion Points are as follows. Here is the pre-meeting deck outlining them all. Each has its own page summarising the relevant data. We'll actively deal with 1-3 in the meeting (i.e. suggestions welcome within the hour), with 4-6 being more community FYIs where we can collate suggestions after the meeting. All discussion points will be covered in our follow up meeting on June 8th (see below for link).

1) Solubility (see #388): How can we make generic improvements in solubility, potentially as a means to improve other factors such as metabolic clearance? Is solubility our key concern?

2) In Vitro In Vivo Correlation (IVIVC) (see #389): How much can we believe the in vitro metabolic clearance data we have on this series? How well do these data correlate with in vivo data? i.e. do we need to demonstrate more clearly an IVIVC, and how might we best do that?

3) Potency (see #390): Based on the SAR to date, what compounds ought we to be targeting (informed by the two issues above) to improve potency?

4) Mechanism of Action (see #391): A next phase of this project is to try to prove the MoA, which is suspected to be via binding to PfATP4. Resources will be needed for a cheminformatic approach to establishing a pharmacophore model.

5) Sourcing Compounds (see #392): What are the most promising untapped resources of existing compounds or synthetic groups interested in collaborating?

6) Interacting with Data (see #393): How can OSM's data and interface be made more user-friendly, particularly to newcomers.

i.e. some overall description of the project for newcomers but mostly a focus on some big-picture science questions for consideration - we'll lay those out between now and the meeting to get the main issues on the table. Paul Willis will say a few things at the start, and Chris Swain will provide guidance on how to play with OSM data.

Follow-up (#394)

Two weeks after this webinar we’ll have a more traditional online meeting where we can garner new inputs or summarize existing suggestions, in order to plan for the next month or so. This is being run independently of Mark: Follow-up meeting location: click here, no need to register. Time: Wed 8th June, same time as first webinar (8am East Coast US, Brazil, 1pm UK, 2pm CET, SAST, 10pm Sydney)

[mattodd]

The meeting recording is here. Thanks to @drc007 for highlighting

[mattodd]

Sidney Burford, a freelance specialist in CMC regulatory affairs and formerly manager of regulatory affairs at Taiho Pharma in Japan, posted a comment during the meeting: "Impressed with SARs and nos. of compounds. Might be time to construct a provisional TPP and get a wish list from clinicians to help prioritize issues e.g. solubility may not be critical. Suggest useful to check plasma binding of more promising compounds so far. Chemistry slightly too dominant at present!"

My reply here: Thanks Sidney. The TPPs are all on the MMV website, and we're aiming there. The dominance of chemistry is not intended, but emerges from my chemistry lab being the grant-funded core (at the moment) and also because synthesis is the roadblock. Comments like yours help redress the balance! Plasma binding - yes, that would be desirable."

Does anyone with expertise in this area have suggestions as for the type of plasma/protein binding experiment and where they could be done?