The Pathogen Box

element-invisible
Catalysing neglected disease drug discovery

Supporting information

The Pathogen Box is supplied free of charge

You can request the Pathogen Box by completing the form on the website. It will be dispatched to you at the earliest opportunity free of charge. In return, you commit to placing your data resulting from research on the Pathogen Box molecules in the public domain within 2 years after its generation; either via the ChEMBL database and/or by publication in a peer-reviewed journal, with an acknowledgement to the source and supply of the compounds.

Publication in an open access journal is strongly encouraged. In the interest of increasing collaboration between researchers, MMV will list the names and contact details of the requestors and those who have reported or published data on the Pathogen Box website.

When you request the box please ensure that you have the resources in place to test it. Challenge grants are only occasionally available to support scientists from disease endemic countries to test these collections. Any related information will be shared on this website.

Screens carried out on the compounds in the Pathogen Box before launch

The individual compounds have only been tested (using a fresh solid sample) to confirm activity against the pathogen for which the compounds were first reported to be active. The compounds have not been tested against the other pathogens represented in the Pathogen Box. Requestors therefore have the opportunity to screen and identify new leads against a particular pathogen (for example finding antimalarial compounds active against cryptosporidium). The compounds have also been tested for cytotoxicity and values are within levels considered acceptable for an initial drug discovery programme (i.e. they are typically 5-fold less potent against the human cell line than the pathogen).

Structures and plate mapping of the 400 compounds

View the structures and plate mapping of the 400 compounds included in the Pathogen Box. This Excel document also includes details on the pathogen against which the compound has shown activity as well as other useful chemical data (compound ID, batch ID, trivial name, molecular weight, salt, cLogP).

Scientific input or advice

MMV would be pleased to hear about the results generated from research on the Pathogen Box. Depending on the query, MMV or a partner organization might also be able to provide you with advice or additional samples to further your work. In particular, building on the funding from the Bill & Melinda Gates Foundation, MMV has received funding from WHO member states for chemistry and target finding of compounds in the Pathogen Box; MMV would be delighted to discuss whether these resources could help your project. Please contact us.

Funding for follow-up work

Scientists in disease endemic countries will be able to apply for ‘Exploiting the Pathogen Box Challenge grants’ in 2016. These are funded by WHO member state countries and details will be announced on the Pathogen Box website. Malaria drug discovery projects, using hits from the Pathogen Box may be eligible to apply for the MMV annual call for proposals. Both funding calls will be advertised on MMV's website and social media platforms. 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. MMV or partners may also be able to provide advice to requestors wishing to apply to other funding agencies.

Malaria Box recipients

We welcome Pathogen Box requests from researchers who have reported the results from screening the Malaria Box. Researchers who have not reported Malaria Box results should do so before applying for the Pathogen Box.

Additional copies of the Pathogen Box

The supplied quantity should be sufficient for most initial screens. In certain instances it might be possible to supply further copies of the Pathogen Box - please reapply via the website including a justification for the additional request. Please note that first time users of the Pathogen Box will be prioritised.

Supply of solid samples of material for hit validation studies

Please contact us to discuss your requirements.

Preparation and shipment of Pathogen Box

Evotec, our compound management partner for the Pathogen Box, will ship sealed plates containing frozen 10 mM dimethyl sulfoxide (DMSO) solutions (10µL of each compound) in 96-well plates, along with handling instructions. 

Recommended procedure for handling the plates

Evotec will inform you by email of the delivery and subsequent handling details. We suggest that the requestor ensures receipt of the Pathogen Box to maintain the plate(s) in a frozen state to prevent cross contamination of wells. 

Recommended procedure for diluting the plates

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.