Open source drug discovery

Highly potent antimalarial compounds derived from the tres cantos arylpyrroles

Alice E Williamson, Paul M Ylioja, Murray N Robertson, Yevgeniya Antonova-Koch, Vicky Avery, Jonathan Baell, Harikrishan Batchu, Sanjay Batra, Jeremy N Burrows, Soumya Bhattacharyya, Felix Calderon, Susan Charman, Julie Clark, Benigno Crespo, Martin Dean, Stefan L Debbert, Michael J Delves, Adelaide S. M Dennis, Frederik Deroose, Sandra Duffy & 3 others Eileen Ryan, Timothy Wells, Karen White

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)687-701
Number of pages15
JournalACS Central Science
Volume2
Issue number10
DOIs
Publication statusPublished - 26 Oct 2016

Cite this

Williamson, A. E., Ylioja, P. M., Robertson, M. N., Antonova-Koch, Y., Avery, V., Baell, J., ... White, K. (2016). Open source drug discovery: Highly potent antimalarial compounds derived from the tres cantos arylpyrroles. ACS Central Science, 2(10), 687-701. https://doi.org/10.1021/acscentsci.6b00086
Williamson, Alice E ; Ylioja, Paul M ; Robertson, Murray N ; Antonova-Koch, Yevgeniya ; Avery, Vicky ; Baell, Jonathan ; Batchu, Harikrishan ; Batra, Sanjay ; Burrows, Jeremy N ; Bhattacharyya, Soumya ; Calderon, Felix ; Charman, Susan ; Clark, Julie ; Crespo, Benigno ; Dean, Martin ; Debbert, Stefan L ; Delves, Michael J ; Dennis, Adelaide S. M ; Deroose, Frederik ; Duffy, Sandra ; Ryan, Eileen ; Wells, Timothy ; White, Karen. / Open source drug discovery : Highly potent antimalarial compounds derived from the tres cantos arylpyrroles. In: ACS Central Science. 2016 ; Vol. 2, No. 10. pp. 687-701.
@article{f4547e883495424d97112f0ac61d8716,
title = "Open source drug discovery: Highly potent antimalarial compounds derived from the tres cantos arylpyrroles",
abstract = "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.",
author = "Williamson, {Alice E} and Ylioja, {Paul M} and Robertson, {Murray N} and Yevgeniya Antonova-Koch and Vicky Avery and Jonathan Baell and Harikrishan Batchu and Sanjay Batra and Burrows, {Jeremy N} and Soumya Bhattacharyya and Felix Calderon and Susan Charman and Julie Clark and Benigno Crespo and Martin Dean and Debbert, {Stefan L} and Delves, {Michael J} and Dennis, {Adelaide S. M} and Frederik Deroose and Sandra Duffy and Eileen Ryan and Timothy Wells and Karen White",
year = "2016",
month = "10",
day = "26",
doi = "10.1021/acscentsci.6b00086",
language = "English",
volume = "2",
pages = "687--701",
journal = "ACS Central Science",
issn = "2374-7943",
publisher = "American Chemical Society",
number = "10",

}

Williamson, AE, Ylioja, PM, Robertson, MN, Antonova-Koch, Y, Avery, V, Baell, J, Batchu, H, Batra, S, Burrows, JN, Bhattacharyya, S, Calderon, F, Charman, S, Clark, J, Crespo, B, Dean, M, Debbert, SL, Delves, MJ, Dennis, ASM, Deroose, F, Duffy, S, Ryan, E, Wells, T & White, K 2016, 'Open source drug discovery: Highly potent antimalarial compounds derived from the tres cantos arylpyrroles', ACS Central Science, vol. 2, no. 10, pp. 687-701. https://doi.org/10.1021/acscentsci.6b00086

Open source drug discovery : Highly potent antimalarial compounds derived from the tres cantos arylpyrroles. / Williamson, Alice E; Ylioja, Paul M; Robertson, Murray N; Antonova-Koch, Yevgeniya; Avery, Vicky; Baell, Jonathan; Batchu, Harikrishan; Batra, Sanjay; Burrows, Jeremy N; Bhattacharyya, Soumya; Calderon, Felix; Charman, Susan; Clark, Julie; Crespo, Benigno; Dean, Martin; Debbert, Stefan L; Delves, Michael J; Dennis, Adelaide S. M; Deroose, Frederik; Duffy, Sandra; Ryan, Eileen; Wells, Timothy; White, Karen.

In: ACS Central Science, Vol. 2, No. 10, 26.10.2016, p. 687-701.

Research output: Contribution to journalArticleResearchpeer-review

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

VL - 2

SP - 687

EP - 701

JO - ACS Central Science

JF - ACS Central Science

SN - 2374-7943

IS - 10

ER -