Update 11/7/12: Our call has been scheduled for TODAY at 1:00 pm Eastern US Time. Email me for dial-in information; Slides are available here .
Update, 10/26/12: Progress has been made on the model, and interest is growing! We’re planning a follow-up call to discuss progress and plans on Nov 7 or 8.
Update, 9/20/12: I’m working to get additional parasitology and med chem folks involved in the discussion before convening the next phone call. Please stay tuned! Watch this space, and follow me on Twitter: @NUTrypKiller
Update, 8/31/12: Slides from our first teleconference to discuss the concept are posted - have a look and see what you think!
The last several years has seen an explosion in interest and opportunity for the discovery of new drugs for neglected tropical diseases (NTDs), such as sleeping sickness, malaria, Chagas disease, leishmaniasis, lymphatic filariasis, and schistosomiasis. Without a doubt, these efforts have been enhanced by the clear description of targeted product profiles, and public sharing of data, primarily from the earliest stages of drug discovery.
This combination of clear goals for optimization and drug-like hit and lead molecules needs to have concerted effort applied to convert these important starting points into new drug therapies.
There is currently little, if any coordination between drug discovery efforts for NTDs. Often, certain attractive chemotypes are pursued by multiple groups, unbeknownst to each other. This represents a serious waste of resource in a very resource-constrained field.
With this in mind, the following sorts of questions often come up:
- I’ve selected excellent leads from the Tres Cantos Antimalarial set. Who else has already pursued these lead classes? Are they still actively working on them? Has this lead class been deprioritized for any reason?
- Has anyone developed structure-activity relationships in related chemotypes?
- Has anyone established a pharmacophore model or identified a target of action for these compounds?
- I have a good parasite growth assay – are there chemists who want to collaborate with me to optimize new compounds?
- I am a chemist branching into NTD drug discovery – what biology groups would like to collaborate?
- What assays and disease models are considered to be the gold standard by MMV or DNDi? Does anyone have these set up?
Let us establish an Open Source NTD drug discovery effort. In this effort we will:
- Discuss parameters for harmonized assay cascades that will be most directive towards the targeted product profiles advanced by MMV, DNDi, and others for new drugs for NTDs. For example – what selectivity assays should be used, in order to be able to compare results? What data do funders actually look for?
- Identify opportunities for organizations (pharma, biotechs, CROs) to provide in-kind contributions of screening resource, in vitro ADME testing, pharmacokinetics, or safety
- Develop a shared database system for use within the group of participants that will allow various levels of collaboration that are within the investigators’ comfort levels, ranging from:
- Annotation of chemotypes under pursuit (minimal data sharing)
- Sharing of all screening data for new compounds (maximal data sharing)
- Coordinate medicinal chemistry efforts where more than one lab is interested in a single chemotype
- Share molecular models (pharmacophore models, homology models, etc)
- Provide opportunities for sharing compounds and information across pathogens. For example – are the inhibitors that are effective against malaria also effective against leishmania?
What’s in it for me? Why would I share my data? I believe that most people who work in NTD drug discovery do so because they truly are looking to cure these diseases of the poor. Sharing goals, data, and strategies can only help accelerate the process, and help ensure that efforts are not wasted. There are some other, more concrete incentives:
- New opportunities for collaboration will be uncovered, which can lead to new funding proposals
- New research tools (compounds, models, scholarship) can help inform your own program
- Higher visibility – we will regularly communicate the progress of our Open Source effort to key stakeholders in NTD drug discovery.
- We will set ground rules within the group regarding data sharing, use of each other’s’ data, and we will work to find good mechanisms of intellectual property management.
What are we not trying to do?
- We are not trying to force anyone to collaborate with anyone.
- We are not trying to become the center of the universe for NTD drug discovery.
- We are not trying to dissuade anyone from pursuit of any chemotypes – only to share information so best decisions can be made by participating investigators.
- We are not trying to establish a shared research portfolio.
- We are not going to dump everyone’s data into the public domain.
- As an Initiative, we don’t necessarily intend to apply for large grants that tie projects together, though we will likely seek funding for database support and other collaboration tools.
Does this sound even a little bit interesting? Then please do the following:
- Please visit this link to provide information about yourself and your interests, and to provide feedback:
- You can email me questions at email@example.com, and follow me on Twitter: @NUTrypkiller #OpenSourceNTD