Targeting de novo purine biosynthesis for tuberculosis treatment
Open accessPublished version of a preprint
Abstract
. Here we report the discovery of a first-in-class small-molecule inhibitor targeting PurF, the first enzyme in the mycobacterial de novo purine biosynthesis pathway. The lead candidate, JNJ-6640, exhibited nanomolar bactericidal activity in vitro. Comprehensive genetic and biochemical approaches confirmed that JNJ-6640 was highly selective for mycobacterial PurF. Single-cell-level microscopy demonstrated a downstream effect on DNA replication. We determined the physiologically relevant concentrations of nucleobases in human and mouse lung tissue, showing that these levels were insufficient to salvage PurF inhibition. Indeed, proof-of-concept studies using a long-acting injectable formulation demonstrated the in vivo efficacy of the compound. Finally, we show that inclusion of JNJ-6640 could have a crucial role in improving current treatment regimens for drug-resistant tuberculosis. Together, we demonstrate that JNJ-6640 is a promising chemical lead and that targeting de novo purine biosynthesis represents a novel strategy for tuberculosis drug development.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Fiji: an open-source platform for biological-image analysis
Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., et al. (2012) · Nature Methods · doi:10.1038/nmeth.2019 · Cited by 66,890 · see citing works
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
Analyzing real-time PCR data by the comparative CT method
Schmittgen, T. D., & Livak, K. J. (2008) · Nature Protocols · doi:10.1038/nprot.2008.73 · Cited by 26,190 · see citing works
Varadi, M., Anyango, S., Deshpande, M., Nair, S., Natassia, C., Yordanova, G., Yuan, D., Stroe, O., Wood, G., Laydon, A., et al. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkab1061 · Cited by 7,850 · see citing works
A Diarylquinoline Drug Active on the ATP Synthase of <i>Mycobacterium tuberculosis</i>
Andries, K., Verhasselt, P., Guillemont, J., Göhlmann, H. W. H., Neefs, J.-M., Winkler, H., Van Gestel, J., Timmerman, P., Zhu, M., Lee, E., et al. (2005) · Science · doi:10.1126/science.1106753 · Cited by 2,191 · see citing works
Identifying and Characterizing Binding Sites and Assessing Druggability
Halgren, T. A. (2009) · Journal of Chemical Information and Modeling · doi:10.1021/ci800324m · Cited by 1,771 · see citing works
Mycobacterial persistence requires the utilization of host cholesterol
Pandey, A. K., & Sassetti, C. M. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711159105 · Cited by 1,064 · see citing works
New Method for Fast and Accurate Binding‐site Identification and Analysis
Halgren, T. (2007) · Chemical Biology & Drug Design · doi:10.1111/j.1747-0285.2007.00483.x · Cited by 880 · see citing works
DeJesus, M. A., Gerrick, E. R., Xu, W., Park, S. W., Long, J. E., Boutte, C. C., Rubin, E. J., Schnappinger, D., Ehrt, S., Fortune, S. M., et al. (2017) · mBio · doi:10.1128/mbio.02133-16 · Cited by 676 · see citing works
Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis
Pethe, K., Bifani, P. J., Jang, J., Kang, S., Park, S., Ahn, S., Jiřiček, J., Jung, J., Jeon, H. K., Cechetto, J. D., et al. (2013) · Nature Medicine · doi:10.1038/nm.3262 · Cited by 601 · see citing works
Daniel, J., Maamar, H., Deb, C., Sirakova, T., & Kolattukudy, P. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002093 · Cited by 595 · see citing works
Voskuil, M. I., Visconti, K. C., & Schoolnik, G. K. (2004) · Tuberculosis · doi:10.1016/j.tube.2004.02.003 · Cited by 448 · see citing works
Genome-wide gene expression tuning reveals diverse vulnerabilities of M. tuberculosis
Bosch, B., DeJesus, M. A., Poulton, N. C., Zhang, W., Engelhart, C. A., Zaveri, A., Lavalette, S., Ruecker, N., Trujillo, C., Wallach, J. B., et al. (2021) · Cell · doi:10.1016/j.cell.2021.06.033 · Cited by 316 · see citing works
Koul, A., Vranckx, L., Dhar, N., Göhlmann, H. W. H., Özdemir, E., Neefs, J., Schulz, M., Lü, P., Mørtz, E., McKinney, J. D., et al. (2014) · Nature Communications · doi:10.1038/ncomms4369 · Cited by 289 · see citing works
Self-citationStructural biology of the purine biosynthetic pathway
Zhang, Y., Morar, M., & Ealick, S. E. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-8295-8 · Cited by 265 · see citing works
Extreme Drug Tolerance of Mycobacterium tuberculosis in Caseum
Sarathy, J. P., Via, L. E., Weiner, D., Blanc, L., Boshoff, H. I., Eugenín, E. A., Barry, C. E., & Dartois, V. A. (2017) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02266-17 · Cited by 225 · see citing works
Self-citationBald, D., Villellas, C., Lü, P., & Koul, A. (2017) · mBio · doi:10.1128/mbio.00272-17 · Cited by 223 · see citing works
Self-citationReliable and Accurate Solution to the Induced Fit Docking Problem for Protein–Ligand Binding
Miller, E. B., Murphy, R. B., Sindhikara, D., Borrelli, K. W., Grisewood, M. J., Ranalli, F., Dixon, S. L., Jerome, S., Boyles, N. A., Day, T., et al. (2021) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.1c00136 · Cited by 210 · see citing works
Krahn, J. M., Kim, J. H., Burns, M. R., Parry, R. J., Zalkin, H., & Smith, J. L. (1997) · Biochemistry · doi:10.1021/bi9714114 · Cited by 183 · see citing works
Single-cell dynamics of the chromosome replication and cell division cycles in mycobacteria
Santi, I., Dhar, N., Bousbaine, D., Wakamoto, Y., & McKinney, J. D. (2013) · Nature Communications · doi:10.1038/ncomms3470 · Cited by 170 · see citing works
Self-citationAn interbacterial toxin inhibits target cell growth by synthesizing (p)ppApp
Ahmad, S., Wang, B., Walker, M. D., Tran, H. R., Stogios, P. J., Savchenko, A. V., Grant, R. A., McArthur, A. G., Laub, M. T., & Whitney, J. C. C. (2019) · Nature · doi:10.1038/s41586-019-1735-9 · Cited by 152 · see citing works
Tweed, C., Dawson, R., Burger, D. A., Conradie, A., Crook, A. M., Mendel, C. M., Conradie, F., Diacon, A. H., Ntinginya, N. E., Everitt, D. E., et al. (2019) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(19)30366-2 · Cited by 142 · see citing works
Efficient measurement and factorization of high-order drug interactions inMycobacterium tuberculosis
Cokol, M., Kuru, N., Bicak, E., Larkins‐Ford, J., & Aldridge, B. B. (2017) · Science Advances · doi:10.1126/sciadv.1701881 · Cited by 128 · see citing works
Self-citationCaseum: a Niche for Mycobacterium tuberculosis Drug-Tolerant Persisters
Sarathy, J., & Dartois, V. (2020) · Clinical Microbiology Reviews · doi:10.1128/cmr.00159-19 · Cited by 115 · see citing works
Self-citationSingh, V., Donini, S., Pacitto, A., Sala, C., Hartkoorn, R. C., Dhar, N., Kéri, G., Ascher, D. B., Mondésert, G., Vocat, A., et al. (2016) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.6b00102 · Cited by 101 · see citing works
Self-citationWasilko, D. J., Lee, S. E., Stutzman-Engwall, K. J., Reitz, B. A., Emmons, T. L., Mathis, K. J., Bienkowski, M. J., Tomasselli, A. G., & Fischer, H. (2009) · Protein Expression and Purification · doi:10.1016/j.pep.2009.01.002 · Cited by 101 · see citing works
Park, Y., Pacitto, A., Bayliss, T., Cleghorn, L. A. T., Wang, Z., Hartman, T. E., Arora, K., Ioerger, T. R., Sacchettini, J. C., Rizzi, M., et al. (2016) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.6b00103 · Cited by 95 · see citing works
Pyrimidine Salvage Pathway in Mycobacterium tuberculosis
Villela, A. D., Sánchez-Quitian, Z. A., Ducati, R. G., Santos, D. S., & Basso, L. A. (2011) · Current Medicinal Chemistry · doi:10.2174/092986711795029555 · Cited by 89 · see citing works
Long-Acting Injectables: Current Perspectives and Future Promise
Chaudhary, K., Patel, M. M., & Mehta, P. J. (2018) · Critical Reviews in Therapeutic Drug Carrier Systems · doi:10.1615/critrevtherdrugcarriersyst.2018025649 · Cited by 77 · see citing works
Larkins‐Ford, J., Greenstein, T., Van, N., Degefu, Y. N., Olson, M. C., Sokolov, A., & Aldridge, B. B. (2021) · Cell Systems · doi:10.1016/j.cels.2021.08.004 · Cited by 76 · see citing works
Self-citationPurine Salvage Pathway in Mycobacterium tuberculosis
Ducati, R. G., Breda, A., Basso, L. A., & Santos, D. S. (2011) · Current Medicinal Chemistry · doi:10.2174/092986711795029627 · Cited by 69 · see citing works
Çevik, M., Thompson, L. C., Upton, C. M., Rolla, V. C., Malahleha, M., Mmbaga, B. T., Ngubane, N., Bakar, Z. A., Rassool, M. S., Variava, E., et al. (2024) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(24)00223-8 · Cited by 64 · see citing works
Larkins‐Ford, J., Degefu, Y. N., Van, N., Sokolov, A., & Aldridge, B. B. (2022) · Cell Reports Medicine · doi:10.1016/j.xcrm.2022.100737 · Cited by 52 · see citing works
Self-citationDrug-Resistant Tuberculosis, KwaZulu-Natal, South Africa, 2001–2007
Wallengren, K., Scano, F., Nunn, P. P., Margot, B., Buthelezi, S. J., Williams, B. G., Pym, A. S., Samuel, E. Y., Mirzayev, F., Nkhoma, W., et al. (2011) · Emerging infectious diseases · doi:10.3201/eid1710.100952 · Cited by 51 · see citing works
Self-citationCoskun, D., Lihan, M., Rodrigues, J., Vass, M., Robinson, D., Friesner, R. A., & Miller, E. B. (2023) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.3c00839 · Cited by 49 · see citing works
Induced-Fit Docking Enables Accurate Free Energy Perturbation Calculations in Homology Models
Xu, T., Zhu, K., Beautrait, A., Vendome, J., Borrelli, K. W., Abel, R., Friesner, R. A., & Miller, E. B. (2022) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.2c00371 · Cited by 45 · see citing works
Linezolid toxicity in patients with drug-resistant tuberculosis: a prospective cohort study
Wasserman, S. A., Brust, J. C. M., Abdelwahab, M. T., Little, F., Denti, P., Wiesner, L., Gandhi, N. R., Meintjes, G., & Maartens, G. (2022) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkac019 · Cited by 44 · see citing works
Uptake‐independent killing of macrophages by extracellular Mycobacterium tuberculosis aggregates
Toniolo, C., Dhar, N., & McKinney, J. D. (2023) · The EMBO Journal · doi:10.15252/embj.2023113490 · Cited by 35 · see citing works
Self-citationCox, J. A. G., Mugumbate, G., Peral, L. V.-G. D., Jankute, M., Abrahams, K. A., Jervis, P. J., Jackenkroll, S., Pérez, A., Alemparte, C., Esquivias, J., et al. (2016) · Scientific Reports · doi:10.1038/srep38986 · Cited by 33 · see citing works
Self-citationRay, P. C., Huggett, M., Turner, P. A., Taylor, M., Cleghorn, L. A. T., Early, J. V., Kumar, A., Bonnett, S. A., Flint, L., Joerss, D., et al. (2021) · ACS Omega · doi:10.1021/acsomega.0c05589 · Cited by 32 · see citing works
Identification of Novel Mt-Guab2 Inhibitor Series Active against M. tuberculosis
Usha, V., Hobrath, J. V., Gurcha, S. S., Reynolds, R. C., & Besra, G. S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033886 · Cited by 31 · see citing works
Akester, J. N., Njaria, P. M., Nchinda, A. T., Manach, C. L., Myrick, A., Singh, V., Lawrence, N., Njoroge, M., Taylor, D., Moosa, A., et al. (2020) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.0c00252 · Cited by 28 · see citing works
Eimer, J., Jachym, M. F., Dû, D. L., Caumes, É., El-Helali, N., Marigot-Outtandy, D., Mechai, F., Peytavin, G., Pourcher, V., Rioux, C., et al. (2022) · Clinical Infectious Diseases · doi:10.1093/cid/ciac485 · Cited by 25 · see citing works
Single-Cell Analysis of Mycobacteria Using Microfluidics and Time-Lapse Microscopy
Dhar, N., & Manina, G. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-2450-9_14 · Cited by 24 · see citing works
Self-citationRamey, M. E., Kaya, F., Bauman, A., Massoudi, L. M., Sarathy, J. P., Zimmerman, M. D., Scott, D. W. L., Job, A. M., Miller-Dawson, J. A., Podell, B. K., et al. (2023) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00597-23 · Cited by 24 · see citing works
Self-citationTransposon sequencing reveals metabolic pathways essential for Mycobacterium tuberculosis infection
Block, A. M., Wiegert, P. C., Namugenyi, S. B., & Tischler, A. D. (2024) · PLoS Pathogens · doi:10.1371/journal.ppat.1011663 · Cited by 16 · see citing works
Lyons, M. A., Obregón‐Henao, A., Ramey, M. E., Bauman, A., Pauly, S., Rossmassler, K., Reid, J. M., Karger, B., Walter, N. D., & Robertson, G. T. (2024) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01010-23 · Cited by 11 · see citing works
Linezolid resistance in patients with drug-resistant TB
Vengurlekar, D., Walker, C., Mahajan, R., Dalal, A., Chavan, V. V., Galindo-Izquierdo, M., Iyer, A., Mansoor, H., Silsarma, A., Isaakidis, P., et al. (2023) · The International Journal of Tuberculosis and Lung Disease · doi:10.5588/ijtld.22.0632 · Cited by 10 · see citing works
Ashwath, P., Osiecki, P., Weiner, D., Via, L. E., & Sarathy, J. P. (2024) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.4c00499 · Cited by 9 · see citing works
Self-citationPhelan, J. E., den Heede, K. V., Masyn, S., Verbeeck, R., Clark, T. G., Lamprecht, D. A., Koul, A., & Wall, R. J. (2024) · Scientific Reports · doi:10.1038/s41598-024-75818-y · Cited by 6 · see citing works
Self-citation
Flagged first, then by citations
2 of the 52 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Antibiotic Resistance: A Genetic and Physiological Perspective
Elbaiomy, R. G., El‐Sappah, A. H., Guo, R., Luo, X., Deng, S., Du, M., Jian, X., Bakeer, M. S., Li, Z., & Zhang, Z. (2025) · MedComm · doi:10.1002/mco2.70447 · Cited by 46 · see citing works
NUDT5 regulates purine metabolism and thiopurine sensitivity by interacting with PPAT
Wu, Z., Nguyen, P. T., Sondhi, V., Yao, R.-W., Lu, Z., Dai, T., Chiang, J., Cai, F., Williams, I. M., Blatt, E. B., et al. (2025) · Science · doi:10.1126/science.adx9717 · Cited by 16 · see citing works
A non-enzymatic role of Nudix hydrolase 5 in repressing purine de novo synthesis
Nguyen, T., Lin, J.-M. G., Marques, A.-S. M. C., Fottner, M., Bauer, L. G., Reicher, A., Daum, D., Scrofani, L., Liu, Y., Cheng, C., et al. (2025) · Science · doi:10.1126/science.adv4257 · Cited by 14 · see citing works
The role of cytochrome bc1 inhibitors in future tuberculosis treatment regimens
Aguilar-Pérez, C., Lenaerts, A. J. M., Villellas, C., Guillemont, J., Dallow, J., Painter, H., Ammerman, N. C., Hassan, A., Golovkine, G. R., Brock, L., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-64427-6 · Cited by 5 · see citing works
Self-citationThe rise of AlphaFold in drug design
Stecuła, A., Paul, R., Litchfield, K., Dalton, S. E., Low, C. M. R., Reis, C. R., & Congreve, M. (2025) · Progress in medicinal chemistry · doi:10.1016/bs.pmch.2025.09.002 · Cited by 4 · see citing works
PurFect timing: revisiting purine metabolism for tuberculosis treatment
Wall, R. J., Mizrahi, V., & Lamprecht, D. A. (2025) · Trends in Microbiology · doi:10.1016/j.tim.2025.10.010 · Cited by 2 · see citing works
Self-citationDe novo or Salvage? Nucleotide Availability as a Driver of Bacterial Adaptation and Virulence
Joshi, R., McEwan, A. G., & Kappler, U. (2026) · MicrobiologyOpen · doi:10.1002/mbo3.70358 · Cited by 2 · see citing works
Ortelli, M., Prakapaitė, R., Müller, A., Miele, S., Fino, C., Klimke, S., Tschudin‐Sutter, S., Jenal, U., Flores, C., Bikard, D., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.31.685768 · Cited by 2 · see citing works
Alberti, M., & Miggiano, R. (2026) · Biochemical Society Transactions · doi:10.1042/bst20253113 · Cited by 1 · see citing works
Zhang, C., Yang, Y., Wang, S., Liu, Y., Zhao, X., Yin, F., Hu, Y., Xue, Y., Bu, Z., Li, S., et al. (2026) · PLoS Pathogens · doi:10.1371/journal.ppat.1013889 · Cited by 1 · see citing works
Structure, Function, and Inhibition of Adenylosuccinate Lyase (ADSL) from Mycobacterium tuberculosis
Singh, V., Jaganathan, D., Corro, J. H., Chen, K., Samrat, S. K., Zhang, R., Ma, M., Battaile, K. P., Li, Z., Zhang, Q., et al. (2025) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.5c00442 · Cited by 1 · see citing works
Exploiting Vitamin B6 Dependency: BVL3572S Inhibits HisC and AlaA to Kill Mycobacterium tuberculosisPreprint
Edoo, Z., Lenne, A., Grosse, C., Devaere, M., Michel, M., Caron, G., Anoz‐Carbonell, E., Djaout, K., Frita, R., Gaudin, C., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.27.684782 · Cited by 1 · see citing works
Phenotypic Screening: A Cornerstone Engine for Discovering Original Anti-Infective Drugs
Xu, S., Wang, M., Shi, D., Lindsley, C. W., Kim, M., Sun, Y., & Zhan, P. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c03538 · Cited by 1 · see citing works
Advances in nucleotide metabolism-targeted drug research
Wang, M., Song, K., Song, Y., Jia, H., & Zhan, P. (2025) · Chinese Chemical Letters · doi:10.1016/j.cclet.2025.112238
Menaquinone depletion resensitises bedaquiline-resistant tuberculosisPreprint
Wetzel, J., Dallow, J., Davis, E., Pearson, W. H., Daems, S., Govaerts, M., Hereijgers, J., Sprangers, J., Truebody, B. E., Maes, V., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.10.702511
Self-citationYu, Y., Zhong, X., Yu, X., Li, J., Liu, H., Liu, X., Jiang, L., & Nie, Z. (2026) · The Analyst · doi:10.1039/d5an01054c
Advances in the Drug Discovery and Development Pipeline and Emerging Drug TargetsPreprint
Tiwari, D., Kaweesa, A. M., Fox, S., & Tiberi, S. (2026) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041851
Li, X., Yang, Y., Wang, P., Nie, T., Hu, X., You, X., Wang, X., & Li, C. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27093880
Singh, V., Zhang, R., Chen, K., Li, Z., & Li, H. (2026) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2026.141167
BVL3572S inhibits HisC and AlaA, exploiting vitamin B6 dependency to kill Mycobacterium tuberculosis
Edoo, Z., Lenne, A., Grosse, C., Devaere, M., Michel, M., Caron, G., Anoz‐Carbonell, E., Djaout, K., Frita, R., Gaudin, C., et al. (2026) · Cell chemical biology · doi:10.1016/j.chembiol.2026.07.008
Nucleotide Metabolism in Health and Disease
Zhao, X., Zeng, Y., Xu, Y., Rao, S., Khouchani, M., Soummane, H., Li, J., & Liu, R. (2026) · MedComm · doi:10.1002/mco2.70900
Dissolution-Controlled Nanocrystalline Rifapentine Formulation for Tuberculosis TreatmentPreprint
Barge, N. S., Kalapala, Y. C., Rajurkar, P., Dravid, A. A., Bhukya, N. K., Saha, R., Sanjay, V., Chakrapani, H., & Agarwal, R. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.08.16.745059
Liu, H., Li, X., Zhang, X., Ge, Y., Chen, Y., Li, X., & Wu, Z. (2026) · Microorganisms · doi:10.3390/microorganisms14081852
Effect size measures in laboratory medicine
Nigussie, N., & Ordak, M. (2026) · Laboratory Medicine · doi:10.1093/labmed/lmag055
Development of GuaB Inhibitors to Treat Mycobacterium tuberculosis Infection
Kofoed, E. M., Crawford, T. D., Bowman, C. M., Sims, J., Dening, T. J., Wang, S., Zhou, Y., Harris, S. F., Xu, M., Wu, P., et al. (2026) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.6c00350
DDU384: A new preclinical candidate for the treatment of TuberculosisPreprint
Green, S. R., Buchanan, K. I., Boshoff, H. I., Koovits, P. J., Murugesan, D., Cozar-Gallardo, C. D., Yepes, A., Hoffmann, E., Massoudi, L. M., Converse, P. J., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.26.760366
- Authors
- Lamprecht, D. A., Wall, R. J., Leemans, A., Truebody, B., Sprangers, J., Fiogbe, P., Davies, C., Wetzel, J., Daems, S., Pearson, W., Pillay, V., Saylock, S., Ricketts, M. D., Davis, E., Huff, A., Grell, T., Lin, S., Gerber, M., Vos, A., Dallow, J., Willcocks, S. J., Roubert, C., Sans, S., Desorme, A., Chappat, N., Ray, A., Pereira Moraes, M., Washington, T., D’Erasmo, H., Sancheti, P., Everaerts, M., Monshouwer, M., Esquivias, J., Larrouy-Maumus, G., Draghia Akli, R., Fletcher, H., Pym, A. S., Aldridge, B. B., Sarathy, J. P., Clancy, K. W., Stoops, B., Dhar, N., Steyn, A. J. C., Jackson, P., Aguilar-Pérez, C., & Koul, A.
- Affiliations
- Janssen (Belgium) (BE)
- London School of Hygiene & Tropical Medicine (GB)
- Africa Health Research Institute (ZA)
- University of Saskatchewan (CA)
- Tufts University (US)
- Imperial College London (GB)
- Janssen (United Kingdom) (GB)
- Hackensack Meridian Health (US)
- University of Alabama at Birmingham (US)
- Janssen (United States) (US)
- Corresponding author
- Lamprecht, Dirk A.
- Koul, Anil
- ORCID
- Lamprecht, Dirk A.
- Wall, Richard J.
- Truebody, Barry
- Daems, Stijn
- Pearson, William
- Grell, Tsehai
- Vos, Ann
- Willcocks, Sam J.
- Sans, Stéphanie
- Pereira Moraes, Mariana
- Washington, Tracy
- D’Erasmo, Hope
- Monshouwer, Mario
- Esquivias, Jorge
- Larrouy-Maumus, Gerald
- Draghia Akli, Ruxandra
- Fletcher, Helen
- Pym, Alexander S.
- Aldridge, Bree B.
- Sarathy, Jansy P.
- Clancy, Kathleen W.
- Stoops, Bart
- Dhar, Neeraj
- Steyn, Adrie J. C.
- Jackson, Paul
- Aguilar-Pérez, Clara
- Koul, Anil
- Venue
- Nature
- Published
- 2025-06-18
- Volume
- 644
- Issue
- 8075
- Pages
- 214-220
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC12328218
- OpenAlex
- W4411413727
- Cited by
- 24
- References
- 52
- Citations by year
- 2026: 13 · 2025: 11
- FWCI
- 7.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature (publishedVersion, cc-by-nc-nd)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- Brunel University Research Archive (BURA) (Brunel University London) (submittedVersion, cc-by-nc-nd)
- Funders
- Wellcome Trust (227167/A/23/Z))
- Innovation Saskatchewan
- Canadian Institutes of Health Research (185715)
- National Institute of Allergy and Infectious Diseases (R33AI138280, R24AI186591)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis and Characterization of Heterocyclic Compounds
- Keywords
- tuberculosis, de novo purine synthesis, purF, small molecule inhibitors, mycobacteria, DNA replication, drug-resistant tuberculosis, long-acting injectables, antitubercular drug development
- MeSH terms
- Proof of Concept Study, Animals, Antitubercular Agents, DNA Replication, Female, Humans, Lung, Male, Mice, Inbred C57BL, Mycobacterium tuberculosis, Purines, Tuberculosis, Tuberculosis, Multidrug-Resistant, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
