TY - JOUR
T1 - Open source drug discovery
T2 - Highly potent antimalarial compounds derived from the tres cantos arylpyrroles
AU - Williamson, Alice E
AU - Ylioja, Paul M
AU - Robertson, Murray N
AU - Antonova-Koch, Yevgeniya
AU - Avery, Vicky
AU - Baell, Jonathan
AU - Batchu, Harikrishan
AU - Batra, Sanjay
AU - Burrows, Jeremy N
AU - Bhattacharyya, Soumya
AU - Calderon, Felix
AU - Charman, Susan
AU - Clark, Julie
AU - Crespo, Benigno
AU - Dean, Martin
AU - Debbert, Stefan L
AU - Delves, Michael J
AU - Dennis, Adelaide S. M
AU - Deroose, Frederik
AU - Duffy, Sandra
AU - Ryan, Eileen
AU - Wells, Timothy
AU - White, Karen
PY - 2016/10/26
Y1 - 2016/10/26
N2 - The development of new antimalarial compounds remains a pivotal part of the strategy for malaria elimination. Recent large-scale phenotypic screens have provided a wealth of potential starting points for hit-to-lead campaigns. One such public set is explored, employing an open source research mechanism in which all data and ideas were shared in real time, anyone was able to participate, and patents were not sought. One chemical subseries was found to exhibit oral activity but contained a labile ester that could not be replaced without loss of activity, and the original hit exhibited remarkable sensitivity to minor structural change. A second subseries displayed high potency, including activity within gametocyte and liver stage assays, but at the cost of low solubility. As an open source research project, unexplored avenues are clearly identified and may be explored further by the community; new findings may be cumulatively added to the present work.
AB - The development of new antimalarial compounds remains a pivotal part of the strategy for malaria elimination. Recent large-scale phenotypic screens have provided a wealth of potential starting points for hit-to-lead campaigns. One such public set is explored, employing an open source research mechanism in which all data and ideas were shared in real time, anyone was able to participate, and patents were not sought. One chemical subseries was found to exhibit oral activity but contained a labile ester that could not be replaced without loss of activity, and the original hit exhibited remarkable sensitivity to minor structural change. A second subseries displayed high potency, including activity within gametocyte and liver stage assays, but at the cost of low solubility. As an open source research project, unexplored avenues are clearly identified and may be explored further by the community; new findings may be cumulatively added to the present work.
UR - http://pubs.acs.org/doi/abs/10.1021/acscentsci.6b00086
U2 - 10.1021/acscentsci.6b00086
DO - 10.1021/acscentsci.6b00086
M3 - Article
AN - SCOPUS:85018343292
SN - 2374-7951
VL - 2
SP - 687
EP - 701
JO - ACS Central Science
JF - ACS Central Science
IS - 10
ER -
