Professor, Department of Chemistry, Faculty of Science; Member of the Institute of Infectious Disease and Molecular Medicine (IDM), UCT; Tier 1 South African National Research Chair in Drug Discovery under the South African Research Chairs Initiative; Director, South African Medical Research Council Drug Discovery and Development Research Unit; Founder and Director, UCT Drug Discovery and Development Centre (H3D)
Kelly Chibale’s drug discovery programme is driven within the H3D Centre at UCT, with laboratory and staff & students partially based in the IDM. Their current target- and phenotypic whole cell-based drug discovery programme against the causative agents of malaria, tuberculosis, antimicrobial resistance (drug resistant infections of bacterial origin) and schistosomiasis infections has the main objective of delivering preclinical drug development candidates. An attendant objective is elucidating the mechanism of action, through target identification, of drug leads derived from the phenotypic whole cell-based approach:
Kelly's earlier work has included asymmetric synthesis utilizing sulfur and organolanthanide chemistry as well as the total synthesis of natural and designed biologically active molecules.
Anti-malarial efficacy and parasite life cycle characterisation of the novel Plasmodium phosphatidylinositol 4-kinase inhibitor MMV390048. T. Paquet, C. Le Manach, D. González Cabrera, Y. Younis, P. P. Henrich, T. S. Abraham, M. C.S. Lee, R. Basak, S. Ghidelli-Disse, M. José Lafuente-Monasterio, M. Bantscheff, A. Ruecker, A. M. Blagborough, S.E. Zakutansky, A.-M. Zeeman, K. L. White, D. M. Shackleford, J. Mannila, J. Morizzi, C. Scheurer, I. Angulo-Barturen, M. S. Martínez, S. Ferrer, L. M. Sanz, F. Javier Gamo, J. Reader, M. Botha, K. J. Dechering, R. W. Sauerwein, A. Tungtaeng, P. Vanachayangkul, C. S. Lim, J. Burrows, M. J. Witty, K. C. Marsh, C. Bodenreider, R. Rochford, S.M. Solapure, M. B. Jiménez-Díaz, S. Wittlin, S. A. Charman, C. Donini, B. Campo, L.-M. Birkholtz, K. K. Hanson, G. Drewes, C. H.M. Kocken, M. J. Delves, D. Leroy, D.A. Fidock, D. Waterson, L. J. Street, and K. Chibale*. Sci. Transl. Med., 2017, 9 (Issue 387), eaad9735 DOI: 10.1126/scitranslmed.aad9735. Published online 26 Apr 2017.
Antischistosomal Activity of pyrido[1,2-a]benzimidazole derivatives and correlation with inhibition of β-haematin formation. J. Okombo, K. Singh, G. Mayoka, F. Ndubi, L. Barnard, P. M. Njogu, M. Njoroge, L. Gibhard, C. Brunschwig, M. Vargas, J. Keiser, T. J. Egan and K. Chibale* ACS Infect. Dis. 2017, 3, 411−420.
Insights into integrated lead generation and target identification in malaria and tuberculosis drug discovery J. Okombo and K. Chibale* Acc. Chem. Res. 2017, 50, 1606−1616.
Novel Anti-tubercular 6-Dialkylaminopyrimidine Carboxamides from Phenotypic Whole-Cell High Throughput Screening of a SoftFocus Library: Structure Activity Relationship and Target Identification Studies. C. Wilson, R. Gessner, A. Moosa, R. Seldon, D. Warner, V. Mizrahi, C. Soares de Melo, S. Simelane, A. Nchinda, E. Abay, D. Taylor, M. Njoroge, C. Brunschwig, N. Lawrence, H. Boshoff, C.E. Barry, F. Sirgel, P. van Helden, C. J. Harris, R. Gordon, S. Ghidelli-Disse, H. Pflaumer, M. Boesche, G. Drewes, O. Sanz, G. Santos, M. J. Rebollo-Lopez, B. Urones, C. Selenski, M. Lafuente-Monasterio, M. Axtman, J. Lelièvre, L. Ballell, R. Mueller; L. Street, S. Ghorpade* and K. Chibale*. J. Med. Chem. 2017, 60, 10118−10134
UCT943, a next generation Plasmodium falciparum PI4K inhibitor preclinical candidate for the treatment of malaria. C. Brunschwig, N. Lawrence, D. Taylor, E. Abay, M. Njoroge, G. S. Basarab, C. Le Manach, T. Paquet, D. G. Cabrera, A. T. Nchinda, C. de Kock, L. Wiesner, P. Denti, D. Waterson, B. Blasco, D. Leroy, M. J. Witty, C. Donini, J. Duffy, S. Wittlin, K. L. White, S. A. Charman, M. B. Jiménez-Díaz, I. Angulo-Barturen, E. Herreros, F. Javier-Gamo, R. Rochford, D. Mancama, T. L. Coetzer, M. E. van der Watt, J. Reader, L.-M. Birkholtz, K. C. Marsh, S. M. Solapure, J. E. Burke, J.A. McPhail, M. Vanaerschot, D. A. Fidock, P. V. Fish, P. Siegl, D. A. Smith, G. Wirjanata, R. Noviyanti, R. N. Price, J. Marfurt, K. D. Silue, L. J. Street, and K. Chibale*. Antimicrob. Agents Chemother. 2018, 62 (Issue 9), e00012-18; doi:10.1128/AAC.00012-18
Plasmodial kinase inhibitors - License to cure?. D. G. Cabrera, A. Horatscheck, C. R. Wilson, G. Basarab, C. J. Eyermann and K. Chibale* J. Med. Chem. 2018, 61, 8061−8077.
Department of Chemistry & IDM
University of Cape Town