Is the Malaria Box really free?
Yes. You can request the Malaria Box simply by completing the form on the MMV website and it will be dispatched to you at the earliest opportunity free of charge. In return, you commit to place your data resulting from research on the Malaria Box in the public domain within 2 years after its generation; either via the ChEMBL database or also publication in a peer-reviewed journal, with an acknowledgement to the source and supply of the compounds. Publication in an open access journal, in particular, is strongly encouraged. In the interests of increasing collaboration between researchers, MMV will list the names and contact details of the requestors on its website.
What screens have been carried out on the compounds in the Malaria Box already?
The compounds were originally tested against the asexual blood stage of P. falciparum by our partners. MMV has then reconfirmed this activity using a fresh solid sample. The compounds have also been tested for cytotoxicity and are within levels considered acceptable for an initial drug discovery programme (i.e. they are typically 10 fold less potent against the human cell line than the P. falciparum target). See supporting information for further details.
Can the Malaria Box be screened against non-antimalarial biological targets?
Yes. Although the Malaria Box is primarily intended to catalyse malaria research, we would be more than happy were it to be screened against other neglected diseases. Given that many antimalarial entities have demonstrated activity against other neglected and parasitic diseases there is good reason to believe the Malaria Box could be gainfully applied in this way.
What kind of hit rates could be expected when screening the Malaria Box against specific biological targets?
The compound selection of the Malaria Box has been based on whole cell screening of the compounds against the malaria parasite. Typical high-throughput screening campaigns have hit rates of <1%. In light of these points it is therefore possible that screening the compounds against a specific malaria/non-malaria target may only generate a few hits, at most.
Will MMV provide scientific input or advice on data generated on the Malaria Box?
MMV would be very pleased to hear about the results generated from research on the Malaria Box. Depending on the query, MMV might also be able to provide you with advice to further your work. Please contact us.
Will MMV provide funding to follow up any interesting results?
MMV does not provide grants for projects, but usually has an annual call for proposals during the first quarter. This is advertised on our website, in Science, Nature and The American Journal of Tropical Medicine and Hygiene. You may also keep informed by signing up for our e-newsletter. All proposals must meet the stipulated criteria of the call and will be evaluated along with all other proposals.
From where do the compounds in the Malaria Box originate?
All compounds present in the Malaria Box originate from the chemical libraries of Novartis-GNF, GlaxoSmithKline and St. Jude Children’s Research Hospital and are commercially available.
What are the characteristics of the drug-like compounds?
The drug-like compounds have been selected to be as diverse as possible while possessing rule-of-5-compliant physicochemical properties (i.e.properties commensurate with oral absorption). However, their oral absorption has not been confirmed through in vitro or in vivo pharmacokinetic studies. Known toxicophores have been removed from this set. These compounds are therefore considered to be those most useful as starting points for drug discovery activities such as lead optimization.
What are the characteristics of the probe-like compounds?
The selection of probe-like compounds is intended to represent the broadest cross-section of structural diversity. They therefore might find most use as tools for probing biological mechanisms of action against a particular target. As some of these compounds do not comply with all of the rule-of-5 physicochemical properties (i.e.properties commensurate with oral absorption) they could be considered to be less useful for drug discovery activities where the intention is to identify orally active compounds.
Are internal antimalarial standards present in the Malaria Box?
No. Each plate has 16 wells left blank to allow your preferred standards to be freshly prepared and added to each plate prior to screening.
My screening resources are limited. Is it possible to receive a smaller selection of compounds?
Yes. MMV has assembled representative selections of 80 and 400 compounds in 96-well-plate formats to suit your screening throughput. The smaller selection contains 40 of the most potent drug-like compounds and 40 of the most potent probe-like compounds.
For more information about the content of each plate please see the supporting information.
Can I order another copy of the Malaria Box?
The supplied quantity should be sufficient for most initial screens. In certain instances it might be possible for MMV to supply further copies of the Malaria Box, please reapply via the website including a justification for the additional request. Please note that first time users of the Malaria Box will be prioritized.
Will MMV supply larger and solid quantities of material for hit validation studies?
Unfortunately not; as a not-for-profit organisation we are only at liberty to supply the initial samples required for research. However, all the compounds in the Malaria Box are commercially available and the details of the suppliers are available on the eMolecules website.
How is the Malaria Box prepared and shipped?
SCYNEXIS will ship sealed plates containing frozen 10 mM dimethyl sulfoxide (DMSO) solutions in 96-well plates along with handling instructions.
Is there a recommended procedure for handling the plate(s)?
Yes. SCYNEXIS will inform you by email of the delivery and subsequent handling details. We suggest that the requestor ensures reception of the Malaria Box to maintain the plate(s) in a frozen state to prevent cross contamination of wells.
Is there a recommended procedure for diluting the plate(s)?
Yes. MMV suggests you perform an intermediate dilution step to generate several copies of the supplied master plate (10 mM stock solution in 100% DMSO). This will avoid multiple freeze/thaw cycles which could lead to the creation of condensation on top of the plates and to an unwanted and unquantifiable dilution of the stock solution. It will also protect the compounds from possible degradation.
Suggested procedure: Dilute the 10 mM stock solution plate to a concentration of 1 mM in 100% DMSO (dilute the initial 10 µL of stock solution into 90 µL of DMSO). 10 plates containing 10 µL solution at 1 mM could then be generated. MMV recommends you test all compounds for screening at a 1µM final concentration and to keep the final volume of DMSO in the reaction buffer as low as possible.