A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemistry programs. The data for all of these assays are presented and analyzed to show how outstanding leads for many indications can be selected. These results reveal the immense potential for translating the dispersed expertise in biological assays involving human pathogens into drug discovery starting points, by providing open access to new families of molecules, and emphasize how a small additional investment made to help acquire and distribute compounds, and sharing the data, can catalyze drug discovery for dozens of different indications. Another lesson is that when multiple screens from different groups are run on the same library, results can be integrated quickly to select the most valuable starting points for subsequent medicinal chemistry efforts.

Leishmaniasis is a tropical disease threatening 350 million people from endemic regions. The available drugs for treatment are inadequate, with limitations such as serious side effects, parasite resistance or high cost. Driven by this need for new drugs, we developed a high-content, high-throughput image-based screening assay targeting the intracellular amastigote stage of different species of Leishmania in infected human macrophages. The in vitro infection protocol was adapted to a 384-well-plate format, enabling acquisition of a large amount of readouts by automated confocal microscopy. The reading method was based on DNA staining and required the development of a customized algorithm to analyze the images, which enabled the use of non-modified parasites. The automated analysis generated parameters used to quantify compound activity, including infection ratio as well as the number of intracellular amastigote parasites and yielded cytotoxicity information based on the number of host cells. Comparison of this assay with one that used the promastigote form to screen 26,500 compounds showed that 50% of the hits selected against the intracellular amastigote were not selected in the promastigote screening. These data corroborate the idea that the intracellular amastigote form of the parasite is the most appropriate to be used in primary screening assay for Leishmania.

A 26 T 35 mm winding diameter all-GdBa2Cu3O (GdBCO) magnet was designed by the MIT Francis Bitter Magnet Laboratory, and constructed and tested by the SuNAM Co., Ltd. With the multi-width (MW) no-insulation (NI) high temperature superconductor (HTS) winding technique incorporated, the magnet is highly compact; its overall diameter and height are 172 and 327 mm, respectively. It consists of a stack of 26 NI double pancake coils wound with MW GdBCO tapes in five different widths ranged 4.1–8.1 mm. In a bath of liquid nitrogen at 77 K, the magnet had a charging time constant of 16 min due to the intrinsic NI characteristics. In liquid helium at 4.2 K, the magnet generated a 26.4 T field at the center, a record high in magnetic fields from all-HTS magnets. The results demonstrate a strong potential of MW-NI GdBCO magnets for direct current high-field applications.

Drugs currently available for leishmaniasis treatment often show parasite resistance, highly toxic side effects and prohibitive costs commonly incompatible with patients from the tropical endemic countries. In this sense, there is an urgent need for new drugs as a treatment solution for this neglected disease. Here we show the development and implementation of an automated high-throughput viability screening assay for the discovery of new drugs against Leishmania. Assay validation was done with Leishmania promastigote forms, including the screening of 4,000 compounds with known pharmacological properties. In an attempt to find new compounds with leishmanicidal properties, 26,500 structurally diverse chemical compounds were screened. A cut-off of 70% growth inhibition in the primary screening led to the identification of 567 active compounds. Cellular toxicity and selectivity were responsible for the exclusion of 78% of the pre-selected compounds. The activity of the remaining 124 compounds was confirmed against the intramacrophagic amastigote form of the parasite. In vitro microsomal stability and cytochrome P450 (CYP) inhibition of the two most active compounds from this screening effort were assessed to obtain preliminary information on their metabolism in the host. The HTS approach employed here resulted in the discovery of two new antileishmanial compounds, bringing promising candidates to the leishmaniasis drug discovery pipeline.

We report in detail on SuNAM's reactive co-evaporation by deposition and reaction (RCE-DR) process. We have successfully fabricated a high performance GdBCO coated conductor (CC) with high throughput by the RCE-DR process, that consists of two steps for the deposition of elemental metal oxides and the conversion of cation oxides into the GdBCO superconducting phase. Constituting metals such as Gd, Ba and Cu were first deposited on LaMnO 3 (LMO)-buffered IBAD-MgO templates at low temperatures and low pressures followed by a high temperature treatment step under high oxygen partial pressure for fast phase conversion. GdBCO CCs fabricated by RCE-DR showed excellent transport properties such as a critical current of 794 A cm −1 width at 77 K in self-field. With the RCE-DR process, we have achieved an overall processing speed of more than 120 m h −1 (in terms of a real process linear tape speed equivalent). SuNAM's RCE-DR technique showed great potential as the highest throughput fabrication process compared with other methods developed previously for second generation high temperature superconducting wires, meeting the current and future need of industry in terms of price and production speed.