Center for Malaria Therapeutics and Antimicrobial Resistance

Displaying 1 - 46 of 46CSV
Godinez-Macias, K. P., Chen, D., Wallis, J. L., Siegel, M. G., Adam, A., Bopp, S., Carolino, K., Coulson, L. B., Durst, G., Thathy, V., Esherick, L., Farringer, M. A., Flannery, E. L., Forte, B., Liu, T., Godoy Magalhaes, L., Gupta, A. K., Istvan, E. S., Jiang, T., … Winzeler, E. A. (2025). Revisiting the Plasmodium falciparum druggable genome using predicted structures and data mining. Npj Drug Discovery, 2(1). https://doi.org/10.1038/s44386-025-00006-5
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Rawat, M., Padalino, G., Adika, E., Okombo, J., Yeo, T., Brancale, A., Fidock, D. A., Hoffmann, K. F., & Lee, M. C. S. (2025). Quinoxaline-based anti-schistosomal compounds have potent anti-plasmodial activity. PLOS Pathogens, 21(2), e1012216. https://doi.org/10.1371/journal.ppat.1012216
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Knaab, T. C., Moritz, A., Pessanha de Carvalho, L., Klein, S., Lungerich, B., Lohse, K., Kruse, L., Mombo-Ngoma, G., Orta, L., Thibaud, J. L., de Villiers, K. A., Fidock, D. A., Burckhardt, B. B., Held, J., Wittlin, S., & Kurz, T. (2024). TKK130 is a 3-Hydroxy-Propanamidine (HPA) with Potent Antimalarial In Vivo Activity and a High Barrier to Resistance. Journal of Medicinal Chemistry. https://doi.org/10.1021/acs.jmedchem.4c01465
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Martinez-Vega, R., Ishengoma, D. S., Gosling, R., Rosenthal, P. J., Dondorp, A., Barnes, K. I., Nsanzabana, C., Djimde, A. A., Ochola-Oyier, L. I., Tibenderana, J., Chimumbwa, J., Golassa, L., Kapologwe, N. A., Mbacham, W. F., Kamya, M. R., Fidock, D. A., Komatsu, R., von Seidlein, L., & Dhorda, M. (2025). Regional action needed to halt antimalarial drug resistance in Africa. The Lancet, 405(10472), 7–10. https://doi.org/10.1016/s0140-6736(24)02706-5
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Hagenah, L. M., Yeo, T., Schindler, K. A., Jeon, J. H., Bloxham, T. S., Small-Saunders, J. L., Mok, S., & Fidock, D. A. (2024). Plasmodium falciparum African PfCRT Mutant Isoforms Conducive to Piperaquine Resistance Are Infrequent and Impart a Major Fitness Cost. The Journal of Infectious Diseases. https://doi.org/10.1093/infdis/jiae617
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Xie, S. C., Tai, C.-W., Morton, C. J., Ma, L., Huang, S.-C., Wittlin, S., Du, Y., Hu, Y., Dogovski, C., Salimimarand, M., Griffin, R., England, D., de la Cruz, E., Deni, I., Yeo, T., Burkhard, A. Y., Striepen, J., Schindler, K. A., Crespo, B., … Tilley, L. (2024). A potent and selective reaction hijacking inhibitor of Plasmodium falciparum tyrosine tRNA synthetase exhibits single dose oral efficacy in vivo. PLOS Pathogens, 20(12), e1012429. https://doi.org/10.1371/journal.ppat.1012429
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Gomez-Gonzalez, P.-J., Gupta, A., Drought, L. G., Patel, A., Okombo, J., van der Watt, M., Walker-Gray, R., Schindler, K. A., Burkhard, A. Y., Yeo, T., Narwal, S. K., Bloxham, T. S., Flueck, C., Walker, E. M., Rey, J. A., Fairhurst, K. J., Reader, J., Park, H., Pollard, H. G., … Baker, D. A. (2024). Inhibitors of malaria parasite cyclic nucleotide phosphodiesterases block asexual blood-stage development and mosquito transmission. Science Advances, 10(49). https://doi.org/10.1126/sciadv.adq1383
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Bestgen, B., Jones, S., Thathy, V., Kuemmerle, A., Barcelo, C., Haouala, A., Gossen, D., Marx, M. W., Di Resta, I., Szramowska, M., Webster, R. A., Llewellyn, S., Ritacco, D. A., Yeo, T., Leroy, D., Barber, B. E., Fidock, D. A., Griffin, P., Lickliter, J., & Chalon, S. (2024). Safety, tolerability, pharmacokinetics, and antimalarial activity of MMV533: a phase 1a first-in-human, randomised, ascending dose and food effect study, and a phase 1b Plasmodium falciparum volunteer infection study. The Lancet Infectious Diseases. https://doi.org/10.1016/s1473-3099(24)00664-9
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Luth, M. R., Godinez-Macias, K. P., Chen, D., Okombo, J., Thathy, V., Cheng, X., Daggupati, S., Davies, H., Dhingra, S. K., Economy, J. M., Edgar, R. C. S., Gomez-Lorenzo, M. G., Istvan, E. S., Jado, J. C., LaMonte, G. M., Melillo, B., Mok, S., Narwal, S. K., Ndiaye, T., … Winzeler, E. A. (2024). Systematic in vitro evolution in Plasmodium falciparum reveals key determinants of drug resistance. Science, 386(6725). https://doi.org/10.1126/science.adk9893
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Ferreira, L. T., Cassiano, G. C., Alvarez, L. C. S., Okombo, J., Calit, J., Fontinha, D., Gil-Iturbe, E., Coyle, R., Andrade, C. H., Sunnerhagen, P., Bargieri, D. Y., Prudêncio, M., Quick, M., Cravo, P. V., Lee, M. C. S., Fidock, D. A., & Costa, F. T. M. (2024). A novel 4-aminoquinoline chemotype with multistage antimalarial activity and lack of cross-resistance with PfCRT and PfMDR1 mutants. PLOS Pathogens, 20(10), e1012627. https://doi.org/10.1371/journal.ppat.1012627
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Brettell, S. B., Janha, O., Begen, A., Cann, G., Sharma, S., Olaniyan, N., Yelland, T., Hole, A. J., Alam, B., Mayville, E., Gillespie, R., Capper, M., Fidock, D. A., Milligan, G., Clarke, D. J., Tobin, A. B., & Jamieson, A. G. (2024). Targeting PfCLK3 with Covalent Inhibitors: A Novel Strategy for Malaria Treatment. Journal of Medicinal Chemistry, 67(21), 18895–18910. https://doi.org/10.1021/acs.jmedchem.4c01300
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Awalt, J. K., Su, W., Nguyen, W., Loi, K., Jarman, K. E., Penington, J. S., Ramesh, S., Fairhurst, K. J., Yeo, T., Park, H., Uhlemann, A.-C., Chandra Maity, B., De, N., Mukherjee, P., Chakraborty, A., Churchyard, A., Famodimu, M. T., Delves, M. J., Baum, J., … Sleebs, B. E. (2024). Exploration and characterization of the antimalarial activity of cyclopropyl carboxamides that target the mitochondrial protein, cytochrome b. European Journal of Medicinal Chemistry, 280, 116921. https://doi.org/10.1016/j.ejmech.2024.116921
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Calic, P. P. S., Ashton, T. D., Mansouri, M., Loi, K., Jarman, K. E., Qiu, D., Lehane, A. M., Roy, S., Rao, G. P., Maity, B., Wittlin, S., Crespo, B., Gamo, F.-J., Deni, I., Fidock, D. A., Chowdury, M., de Koning-Ward, T. F., Cowman, A. F., Jackson, P. F., … Sleebs, B. E. (2024). Optimization of pyrazolopyridine 4-carboxamides with potent antimalarial activity for which resistance is associated with the P. falciparum transporter ABCI3. European Journal of Medicinal Chemistry, 276, 116677. https://doi.org/10.1016/j.ejmech.2024.116677
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Bennett, J. M., Narwal, S. K., Kabeche, S., Abegg, D., Thathy, V., Hackett, F., Yeo, T., Li, V. L., Muir, R., Faucher, F., Lovell, S., Blackman, M. J., Adibekian, A., Yeh, E., Fidock, D. A., & Bogyo, M. (2024). Mixed alkyl/aryl phosphonates identify metabolic serine hydrolases as antimalarial targets. Cell Chemical Biology, 31(9), 1714-1728.e10. https://doi.org/10.1016/j.chembiol.2024.07.006
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Lawong, A., Gahalawat, S., Ray, S., Ho, N., Han, Y., Ward, K. E., Deng, X., Chen, Z., Kumar, A., Xing, C., Hosangadi, V., Fairhurst, K. J., Tashiro, K., Liszczak, G., Shackleford, D. M., Katneni, K., Chen, G., Saunders, J., Crighton, E., … Phillips, M. A. (2024). Identification of potent and reversible piperidine carboxamides that are species-selective orally active proteasome inhibitors to treat malaria. Cell Chemical Biology, 31(8), 1503-1517.e19. https://doi.org/10.1016/j.chembiol.2024.07.001
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Rosado-Quiñones, A. M., Colón-Lorenzo, E. E., Pala, Z. R., Bosch, J., Kudyba, K., Kudyba, H., Leed, S. E., Roncal, N., Baerga-Ortiz, A., Roche-Lima, A., Gerena, Y., Fidock, D. A., Roth, A., Vega-Rodríguez, J., & Serrano, A. E. (2024). Novel hydrazone compounds with broad-spectrum antiplasmodial activity and synergistic interactions with antimalarial drugs. Antimicrobial Agents and Chemotherapy. https://doi.org/10.1128/aac.01643-23
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Small-Saunders, J. L., Sinha, A., Bloxham, T. S., Hagenah, L. M., Sun, G., Preiser, P. R., Dedon, P. C., & Fidock, D. A. (2024). tRNA modification reprogramming contributes to artemisinin resistance in Plasmodium falciparum. Nature Microbiology, 9(6), 1483–1498. https://doi.org/10.1038/s41564-024-01664-3
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Nguyen, W., Boulet, C., Dans, M. G., Loi, K., Jarman, K. E., Watson, G. M., Tham, W.-H., Fairhurst, K. J., Yeo, T., Fidock, D. A., Wittlin, S., Chowdury, M., de Koning-Ward, T. F., Chen, G., Yan, D., Charman, S. A., Baud, D., Brand, S., Jackson, P. F., … Sleebs, B. E. (2024). Activity refinement of aryl amino acetamides that target the P. falciparum STAR-related lipid transfer 1 protein. European Journal of Medicinal Chemistry, 270, 116354. https://doi.org/10.1016/j.ejmech.2024.116354
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Rosenthal, P. J., Asua, V., Bailey, J. A., Conrad, M. D., Ishengoma, D. S., Kamya, M. R., Rasmussen, C., Tadesse, F. G., Uwimana, A., & Fidock, D. A. (2024). The emergence of artemisinin partial resistance in Africa: how do we respond? The Lancet Infectious Diseases. https://doi.org/10.1016/s1473-3099(24)00141-5
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Xie, S. C., Wang, Y., Morton, C. J., Metcalfe, R. D., Dogovski, C., Pasaje, C. F. A., Dunn, E., Luth, M. R., Kumpornsin, K., Istvan, E. S., Park, J. S., Fairhurst, K. J., Ketprasit, N., Yeo, T., Yildirim, O., Bhebhe, M. N., Klug, D. M., Rutledge, P. J., Godoy, L. C., … Tilley, L. (2024). Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase. Nature Communications, 15(1). https://doi.org/10.1038/s41467-024-45224-z
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Hagenah, L. M., Dhingra, S. K., Small-Saunders, J. L., Qahash, T., Willems, A., Schindler, K. A., Rangel, G. W., Gil-Iturbe, E., Kim, J., Akhundova, E., Yeo, T., Okombo, J., Mancia, F., Quick, M., Roepe, P. D., Llinás, M., & Fidock, D. A. (2024). Additional PfCRT mutations driven by selective pressure for improved fitness can result in the loss of piperaquine resistance and altered Plasmodium falciparum physiology. MBio, 15(1). https://doi.org/10.1128/mbio.01832-23
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Kümpornsin, K., Kochakarn, T., Yeo, T., Okombo, J., Luth, M. R., Hoshizaki, J., Rawat, M., Pearson, R. D., Schindler, K. A., Mok, S., Park, H., Uhlemann, A.-C., Jana, G. P., Maity, B. C., Laleu, B., Chenu, E., Duffy, J., Moliner Cubel, S., Franco, V., … Lee, M. C. S. (2023). Generation of a mutator parasite to drive resistome discovery in Plasmodium falciparum. Nature Communications, 14(1). https://doi.org/10.1038/s41467-023-38774-1
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Bopp, S., Pasaje, C. F. A., Summers, R. L., Magistrado-Coxen, P., Schindler, K. A., Corpas-Lopez, V., Yeo, T., Mok, S., Dey, S., Smick, S., Nasamu, A. S., Demas, A. R., Milne, R., Wiedemar, N., Corey, V., Gomez-Lorenzo, M. D. G., Franco, V., Early, A. M., Lukens, A. K., … Wirth, D. F. (2023). Potent acyl-CoA synthetase 10 inhibitors kill Plasmodium falciparum by disrupting triglyceride formation. Nature Communications, 14(1). https://doi.org/10.1038/s41467-023-36921-2
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Stadler, E., Maiga, M., Friedrich, L., Thathy, V., Demarta-Gatsi, C., Dara, A., Sogore, F., Striepen, J., Oeuvray, C., Djimdé, A. A., Lee, M. C. S., Dembélé, L., Fidock, D. A., Khoury, D. S., & Spangenberg, T. (2023). Propensity of selecting mutant parasites for the antimalarial drug cabamiquine. Nature Communications, 14(1). https://doi.org/10.1038/s41467-023-40974-8
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Mok, S., Yeo, T., Hong, D., Shears, M. J., Ross, L. S., Ward, K. E., Dhingra, S. K., Kanai, M., Bridgford, J. L., Tripathi, A. K., Mlambo, G., Burkhard, A. Y., Ansbro, M. R., Fairhurst, K. J., Gil-Iturbe, E., Park, H., Rozenberg, F. D., Kim, J., Mancia, F., … Fidock, D. A. (2023). Mapping the genomic landscape of multidrug resistance in Plasmodium falciparum and its impact on parasite fitness. Science Advances, 9(45). https://doi.org/10.1126/sciadv.adi2364
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Siqueira-Neto, J. L., Wicht, K. J., Chibale, K., Burrows, J. N., Fidock, D. A., & Winzeler, E. A. (2023). Antimalarial drug discovery: progress and approaches. Nature Reviews Drug Discovery, 22(10), 807–826. https://doi.org/10.1038/s41573-023-00772-9
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van der Plas, J. L., Kuiper, V. P., Bagchus, W. M., Bödding, M., Yalkinoglu, Ö., Tappert, A., Seitzinger, A., Spangenberg, T., Bezuidenhout, D., Wilkins, J., Oeuvray, C., Dhingra, S. K., Thathy, V., Fidock, D. A., Smidt, L. C. A., Roozen, G. V. T., Koopman, J. P. R., Lamers, O. A. C., Sijtsma, J., … Khandelwal, A. (2023). Causal chemoprophylactic activity of cabamiquine against Plasmodium falciparum in a controlled human malaria infection: a randomised, double-blind, placebo-controlled study in the Netherlands. The Lancet Infectious Diseases, 23(10), 1164–1174. https://doi.org/10.1016/s1473-3099(23)00212-8
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Bennett, J. M., Ward, K. E., Muir, R. K., Kabeche, S., Yoo, E., Yeo, T., Lam, G., Zhang, H., Almaliti, J., Berger, G., Faucher, F. F., Lin, G., Gerwick, W. H., Yeh, E., Fidock, D. A., & Bogyo, M. (2023). Covalent Macrocyclic Proteasome Inhibitors Mitigate Resistance in Plasmodium falciparum. ACS Infectious Diseases, 9(10), 2036–2047. https://doi.org/10.1021/acsinfecdis.3c00310
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Armstrong, J. F., Campo, B., Alexander, S. P. H., Arendse, L. B., Cheng, X., Davenport, A. P., Faccenda, E., Fidock, D. A., Godinez‐Macias, K. P., Harding, S. D., Kato, N., Lee, M. C. S., Luth, M. R., Mazitschek, R., Mittal, N., Niles, J. C., Okombo, J., Ottilie, S., Pasaje, C. F. A., … Davies, J. A. (2023). Advances in malaria pharmacology and the online guide to MALARIA PHARMACOLOGY: IUPHAR review 38. British Journal of Pharmacology, 180(15), 1899–1929. Portico. https://doi.org/10.1111/bph.16144
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Ward, K. E., Christensen, P., Racklyeft, A., Dhingra, S. K., Chua, A. C. Y., Remmert, C., Suwanarusk, R., Matheson, J., Blackman, M. J., Kaneko, O., Kyle, D. E., Lee, M. C. S., Moon, R. W., Snounou, G., Rénia, L., Fidock, D. A., Russell, B., & Bifani, P. (2022). Integrative Genetic Manipulation of Plasmodium cynomolgi Reveals Multidrug Resistance-1 Y976F Associated With Increased In Vitro Susceptibility to Mefloquine. The Journal of Infectious Diseases, 227(10), 1121–1126. https://doi.org/10.1093/infdis/jiac469
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Deni, I., Stokes, B. H., Ward, K. E., Fairhurst, K. J., Pasaje, C. F. A., Yeo, T., Akbar, S., Park, H., Muir, R., Bick, D. S., Zhan, W., Zhang, H., Liu, Y. J., Ng, C. L., Kirkman, L. A., Almaliti, J., Gould, A. E., Duffey, M., O’Donoghue, A. J., … Fidock, D. A. (2023). Mitigating the risk of antimalarial resistance via covalent dual-subunit inhibition of the Plasmodium proteasome. Cell Chemical Biology, 30(5), 470-485.e6. https://doi.org/10.1016/j.chembiol.2023.03.002
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Ashton, T. D., Dans, M. G., Favuzza, P., Ngo, A., Lehane, A. M., Zhang, X., Qiu, D., Chandra Maity, B., De, N., Schindler, K. A., Yeo, T., Park, H., Uhlemann, A.-C., Churchyard, A., Baum, J., Fidock, D. A., Jarman, K. E., Lowes, K. N., Baud, D., … Sleebs, B. E. (2023). Optimization of 2,3-Dihydroquinazolinone-3-carboxamides as Antimalarials Targeting PfATP4. Journal of Medicinal Chemistry, 66(5), 3540–3565. https://doi.org/10.1021/acs.jmedchem.2c02092
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Istvan, E. S., Guerra, F., Abraham, M., Huang, K.-S., Rocamora, F., Zhao, H., Xu, L., Pasaje, C., Kumpornsin, K., Luth, M. R., Cui, H., Yang, T., Palomo Diaz, S., Gomez-Lorenzo, M. G., Qahash, T., Mittal, N., Ottilie, S., Niles, J., Lee, M. C. S., … Winzeler, E. A. (2023). Cytoplasmic isoleucyl tRNA synthetase as an attractive multistage antimalarial drug target. Science Translational Medicine, 15(686). https://doi.org/10.1126/scitranslmed.adc9249
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Kucharski, M., Wirjanata, G., Nayak, S., Boentoro, J., Dziekan, J. M., Assisi, C., van der Pluijm, R. W., Miotto, O., Mok, S., Dondorp, A. M., & Bozdech, Z. (2023). Short tandem repeat polymorphism in the promoter region of cyclophilin 19B drives its transcriptional upregulation and contributes to drug resistance in the malaria parasite Plasmodium falciparum. PLOS Pathogens, 19(1), e1011118. https://doi.org/10.1371/journal.ppat.1011118
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Wicht, K. J., Small-Saunders, J. L., Hagenah, L. M., Mok, S., & Fidock, D. A. (2022). Mutant PfCRT Can Mediate Piperaquine Resistance in African Plasmodium falciparum With Reduced Fitness and Increased Susceptibility to Other Antimalarials. The Journal of Infectious Diseases, 226(11), 2021–2029. https://doi.org/10.1093/infdis/jiac365
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de Vries, L. E., Jansen, P. A. M., Barcelo, C., Munro, J., Verhoef, J. M. J., Pasaje, C. F. A., Rubiano, K., Striepen, J., Abla, N., Berning, L., Bolscher, J. M., Demarta-Gatsi, C., Henderson, R. W. M., Huijs, T., Koolen, K. M. J., Tumwebaze, P. K., Yeo, T., Aguiar, A. C. C., Angulo-Barturen, I., … Dechering, K. J. (2022). Preclinical characterization and target validation of the antimalarial pantothenamide MMV693183. Nature Communications, 13(1). https://doi.org/10.1038/s41467-022-29688-5
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Okombo, J., Mok, S., Qahash, T., Yeo, T., Bath, J., Orchard, L. M., Owens, E., Koo, I., Albert, I., Llinás, M., & Fidock, D. A. (2022). Piperaquine-resistant PfCRT mutations differentially impact drug transport, hemoglobin catabolism and parasite physiology in Plasmodium falciparum asexual blood stages. PLOS Pathogens, 18(10), e1010926. https://doi.org/10.1371/journal.ppat.1010926
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Arendse, L. B., Murithi, J. M., Qahash, T., Pasaje, C. F. A., Godoy, L. C., Dey, S., Gibhard, L., Ghidelli-Disse, S., Drewes, G., Bantscheff, M., Lafuente-Monasterio, M. J., Fienberg, S., Wambua, L., Gachuhi, S., Coertzen, D., van der Watt, M., Reader, J., Aswat, A. S., Erlank, E., … Chibale, K. (2022). The anticancer human mTOR inhibitor sapanisertib potently inhibits multiple Plasmodium kinases and life cycle stages. Science Translational Medicine, 14(667). https://doi.org/10.1126/scitranslmed.abo7219
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Ward, K. E., Fidock, D. A., & Bridgford, J. L. (2022). Plasmodium falciparum resistance to artemisinin-based combination therapies. Current Opinion in Microbiology, 69, 102193. https://doi.org/10.1016/j.mib.2022.102193
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Qiu, D., Pei, J. V., Rosling, J. E. O., Thathy, V., Li, D., Xue, Y., Tanner, J. D., Penington, J. S., Aw, Y. T. V., Aw, J. Y. H., Xu, G., Tripathi, A. K., Gnadig, N. F., Yeo, T., Fairhurst, K. J., Stokes, B. H., Murithi, J. M., Kümpornsin, K., Hasemer, H., … Lehane, A. M. (2022). A G358S mutation in the Plasmodium falciparum Na+ pump PfATP4 confers clinically-relevant resistance to cipargamin. Nature Communications, 13(1). https://doi.org/10.1038/s41467-022-33403-9
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Kanai, M., Hagenah, L. M., Ashley, E. A., Chibale, K., & Fidock, D. A. (2022). Keystone Malaria Symposium 2022: a vibrant discussion of progress made and challenges ahead from drug discovery to treatment. Trends in Parasitology, 38(9), 711–718. https://doi.org/10.1016/j.pt.2022.06.005
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Small-Saunders, J. L., Hagenah, L. M., Wicht, K. J., Dhingra, S. K., Deni, I., Kim, J., Vendome, J., Gil-Iturbe, E., Roepe, P. D., Mehta, M., Mancia, F., Quick, M., Eppstein, M. J., & Fidock, D. A. (2022). Evidence for the early emergence of piperaquine-resistant Plasmodium falciparum malaria and modeling strategies to mitigate resistance. PLOS Pathogens, 18(2), e1010278. https://doi.org/10.1371/journal.ppat.1010278
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