- RFP Year2020
- Awarded Amount$80,000
- DiseaseNTD (Chagas disease / Leishmaniasis)
- Development StageHit Identification
- Collaboration PartnersDaiichi Sankyo RD Novare Co., Ltd., Drugs for Neglected Diseases initiative
- Past Project
1. Project objective
This is a continuation of the screening conducted by DNDi and Daiichi Sankyo RD Novare (S2017-221) that aims to screen Daiichi Sankyo RD Novare’s natural product collection of fermentation extracts (30,000 samples) against T. cruzi and L. donovani to identify hit compounds and evaluate potential progression into the Hit-to-Lead stage.
2. Project design
Based on T. cruzi and L. donovani. activity data from the S2017-221 project, a total of 17 fermented extracts were selected for further investigation. The dereplication and bio-guided fractionation of the newly fermented extracts has been completed for those 17 natural products producing microbial strains. Based on this data, isolation of the active ingredients from the 3 most promising strains was undertaken and successfully completed for 2 of them.
3. Results, lessons learned
A new chemical series of interest has been identified as well as chemically and biologically characterised with respect to activity against T. cruzi and L. donovani. In addition, a structurally unrelated singleton of interest was identified, and its biological activity against these target characterized, as well. Due to the limited number of hits identified and early-stage profiles of these hits, it was decided that proposing a Hit-to-Lead program would not be realistic at this time. Further biological profiling of the hit compounds obtained will be conducted at DNDi’s on an in-kind basis, expecting that these hits may serve as novel probes for further mechanism of action studies and, perhaps, eventually a Target Research Platform proposal.
In terms of lessons learned, as we already knew, the isolation and identification of pure compounds from fermentation extract is a complicated and difficult process, and thus challenging to complete in a short period of time on schedule. We feel that such efforts are worth the investment of time and resources in order to identify new molecular entities, as long as the risk of long timelines and not being able to identify all active compounds is understood by all parties involved. Putting in place a clear process with regard to the prioritization/discontinuation of the strains/extracts/fractions under consideration for hit identification is key for this type of project to allow a rational allocation of the work resources as well as management of the project timelines and objectives.