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1 Promiscuous targets have been proven really useful for the development of novel antitubercular drug candidates. This is well demonstrated by the fact that five compounds currently in clinical trials inhibit these targets, including DprE1 and MmpL3. + 1313 word(s) 1313 2020-08-19 04:38:07 |
2 format correct Meta information modification 1313 2020-08-23 13:59:43 | |
3 format correction Meta information modification 1313 2020-10-27 11:53:35 |

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Degiacomi, G.; Belardinelli, J.M.; Pasca, M.R.; De Rossi, E.; Riccardi, G.; Chiarelli, L.R. DprE1 and MmpL3. Encyclopedia. Available online: (accessed on 20 May 2024).
Degiacomi G, Belardinelli JM, Pasca MR, De Rossi E, Riccardi G, Chiarelli LR. DprE1 and MmpL3. Encyclopedia. Available at: Accessed May 20, 2024.
Degiacomi, Giulia, Juan Manuel Belardinelli, Maria Rosalia Pasca, Edda De Rossi, Giovanna Riccardi, Laurent Roberto Chiarelli. "DprE1 and MmpL3" Encyclopedia, (accessed May 20, 2024).
Degiacomi, G., Belardinelli, J.M., Pasca, M.R., De Rossi, E., Riccardi, G., & Chiarelli, L.R. (2020, August 20). DprE1 and MmpL3. In Encyclopedia.
Degiacomi, Giulia, et al. "DprE1 and MmpL3." Encyclopedia. Web. 20 August, 2020.
DprE1 and MmpL3

DprE1 is an enzyme that works in concert with DprE2 to synthesize the unique arabinose precursor for lipoarabinomannan and arabinogalactan, essential building blocks of the mycobacterial cell-wall [1]. To date, more than 15 pharmacophores were found to inhibit DprE1 activity. MmpL3 is the only Mtb transporter of trehalose monomycolate, required for the formation of the mycolic acid layer of the cell wall [2], and has been found to be affected by several molecules. Recently, direct inhibition of MmpL3 by BM212, the first compound found to hit MmpL3, was shown using spheroplasts [2], while the dissipation of proton motive force is the proposed mechanism for the other molecules [3].

mycobacteria tuberculosis multi-drug resistance drug discovery promiscuous targets

1. Introduction 

One of the biggest problems in fighting Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), is the development and spread of multi-drug resistant strains [4]. Therefore, there is an urgent need to identify novel druggable targets for the development of more efficient anti-TB agents [5][6]. In this context, the medicinal chemistry efforts made in the last years led to the discovery of new antimycobacterial compounds, and the identification of novel targets [6][7][8].

High-throughput screenings (HTS), based on Mtb whole cells, were developed to identify hit compounds with potent inhibitory activity, and consequently, new targets emerged. The HTS had the merit of fueling the scarce TB drug development pipeline, since many molecules under preclinical and clinical development came out from this approach. Indeed, the first new TB drug, Bedaquiline, approved by the Food and Drug Administration (FDA) since 1971, was discovered in a whole-cell HTS campaign [9], and the same origin had both Delamanid [10] and Pretomanid [11], other two drugs recently approved for multidrug resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) treatment [12][13].

Curiously, an unforeseen outcome of many phenotypic screens against Mtb is the finding that the same targets have been frequently found in many different screening assays, despite the use of different compound libraries [14]. These targets were named “promiscuous” targets, for their nonspecific susceptibility to being inhibited by different scaffolds [5][15]. Although this term was initially given with a negative connotation, the value of these potential pharmacological targets has been reevaluated. Indeed, the high vulnerability of these essential targets, reflecting the biggest vulnerabilities of Mtb, can provide new opportunities to be explored for the development of TB drugs [15]. Among them, there are DprE1, MmpL3, QcrB and Psk13 [6][16]. It is noteworthy that several research groups independently identified these promiscuous targets. These proteins are embedded in pathways that have key roles for Mtb growth and survival under the screening conditions, but even more important during infection. Their essentiality represents an Mtb Achilles' heel that is important to exploit for the development of new effective drug regimens able to shorten the TB treatment. Interestingly, all these promiscuous targets are localized within the cell envelope, emphasizing that the cell wall still represents a fruitful source of drug targets.

2. The First Discovery of DprE1 and MmpL3 as Drug Target

Dr. Vadim Makarov and collaborators, including our Laboratory, published in 2009 the first report in which DprE1 was described as the target of 1,3-benzothiazin-4-ones (BTZ), a new class of agents endowed with antimycobacterial activity [17]. To find the BTZ target, two genetic approaches were performed in parallel using both a Mycobacterium smegmatis cosmid library for resistance to BTZ, and the selection and characterization of M. smegmatis, Mycobacterium bovis BCG and M. tuberculosis spontaneous resistant mutants. Both methods revealed that dprE1 gene was responsible for BTZ resistance. It is noteworthy that all the mutants carried mutations in the same codon of dprE1, leading to the replacement of Cys387 with a Ser or Gly residue [17]. DprE1 was known to be involved in the arabinogalactan biosynthesis, a key precursor required for the synthesis of the cell-wall [1][18], and it was demonstrated that its inhibition abolishes the formation of decaprenylphosphoryl arabinose (DPA), thus provoking cell lysis and bacterial death [17]. Later, new antimycobacterial compounds targeting DprE1 were identified by independent whole cell-based screens, like dinitrobenzamides (DNB) and bromoquinoxaline (VI-9376) [19][20], and afterward, numerous DprE1 inhibitors have come out since that groundbreaking report in 2009.

MmpL3 was firstly identified in our laboratory as the cellular target of BM212, the hit compound of pyrrole-derivative class of antimycobacterial agents by screening the M. smegmatis cosmid library for BM212 resistance, as well as the selection and characterization of spontaneous resistant mutants [21]. Immediately after this first publication, MmpL3 was demonstrated to be the target of SQ109, an antitubercular in clinical trials, for which the mechanism of action was still unclear, and adamantyl urea AU1235, a compound displaying potent bactericidal activity against Mtb [22][23]. Genetic and biochemical studies indicated a clear effect of inhibiting MmpL3 on the translocation of trehalose monomycolate (TMM) in Mtb, thus abolishing the trehalose dimycolate (TDM) formation and mycolic acid transfer onto arabinogalactan [22][23]. Subsequently, several papers have reported the discovery of new MmpL3 inhibitors.

3. DprE1: The Hot TB Target of the Moment

DprE1 (Decaprenylphosphoryl-β-d-ribofuranose 2-oxidoreductase, EC, is involved along with DprE2 (Decaprenylphosphoryl-2-keto-β-d-erythro-pentose reductase, EC, in the two-step epimerization of decaprenylphosphoribose (DPR) to decaprenylphosphoarabinose (DPA), a key arabinosyl donor essential for the biosynthesis of cell-wall arabinan polymers [24]. The conversion of DPR to DPA is a two steps reaction, in which the product of DprE1 decaprenyl-phospho-2′-keto-d-arabinose must be reduced to finalize the epimerization of the substrate. This second step is catalyzed by the enzyme DprE2 (decaprenylphosphoryl-2-keto-β-d-erythro-pentose reductase) [1]. As DprE1, also DprE2 is essential for mycobacterial growth [25]. Moreover, the two enzymes have been supposed to strongly interact, and sometimes they were considered two subunits of a single enzyme named decaprenylphosphoryl-β-d-ribofuranose 2-epimerase.

Currently, at least 11 different scaffolds have been reported as effective DprE1 inhibitors, either covalent and noncovalent, showing different efficacy in vitro, ex vivo and in vivo [26]. It is noteworthy that the majority of these compounds have been identified through phenotypic screening, then subjected to optimization processes.

The first DprE1 inhibitors identified is the BTZ043, belonging to the class of the benzothiazinones [17], and extremely potent against M. tuberculosis with an MIC of 1 ng/ml (2.3 nM) [17]. SAR study of piperazine benzothiazinone derivatives afforded the PBTZ-169 [27], with improved in -vitro and in-vivo potency, which is currently in clinical trial under the name of macozinone [28].

The high vulnerability of DprE1 as an antitubercular drug target was confirmed by the number of screening campaigns that identified effective non-covalent inhibitors, including thiadiazoles [29], carboxy-quinoxalines [30], aminoquinolones [31], pyrazolopyridones [32], and azaindoles [33][34]. The latter are the most promising drug candidates among the non-covalent DprE1 inhibitors. Currently, the azaindole TBA-7371 has started phase 1 clinical trial [35], further confirming the great potential of DprE1 inhibitors in anti-tubercular drug discovery.

4. Mmpl3 Transporter: The Other Hot TB Target of the Moment

MmpL3 is a membrane protein, member of the resistance-nodulation-cell division (RND) superfamily of transporters. In mycobacteria, MmpL transporters have specialized in the export of several lipids and glycolipids across the plasma membrane to the cell surface, namely, trehalose monomycolates (TMM), di- and poly-acyltrehaloses, sulfolipids, phthiocerol dimycocerosates, monomycolyldiacylglycerol, glycopeptidolipids and mycobactins [23][36][37][38][39][40]. Genetic studies with transposon mutant libraries and the inability to knock-out the gene using different strategies suggested that MmpL3 was essential for the survival of M. tuberculosis [23][41]. An alternative strategy, utilizing knock-down strains both in vitro and in vivo had confirmed that MmpL3 is indeed essential for survival. Silencing of MmpL3 in mice, both during the acute or persistence phase of infection, led to a complete clearance of bacteria from lungs and spleens. These studies not only reinforce the idea of MmpL3 as an attractive drug target but also the potential of MmpL3 inhibitors to shorten TB treatment [42].

In recent years, a diversity of scaffolds have been reported to inhibit MmpL3: SQ109 (diamine), DA5 (SQ109 related compound), BM212 (diarylpyrrole), Au1235 (adamantyl urea), C215 (benzimidazole), NITD-349 (indolecarboxamides), THP P (tetrathydropyrazolo pyrimidine), Spiro (N-benzyl-6′,7′-dihydrospiro[piperidine-4,4′-thieno[3,2-c]pyrans]), PIPD1 (piperidinol), E11 (acetamide) and HC2091 (carboxamide) [21][22][23][43][44][45][46][47][48].

These findings will lead to a new era in MmpL3 inhibitor drug discovery since structure-guided molecules can now be designed with better anti-tubercular efficacy and pharmacokinetic/pharmacodynamic (PK/PD) properties.


  1. Mikusová, K.; Huang, H.; Yagi, T.; Holsters, M.; Vereecke, D.; D’Haeze, W.; Scherman, M.S.; Brennan, P.J.; McNeil, M.R.; Crick, D.C. Decaprenylphosphoryl arabinofuranose, the donor of the D-arabinofuranosyl residues of mycobacterial arabinan, is formed via a two-step epimerization of decaprenylphosphoryl ribose. J. Bacteriol. 2005, 187, 8020–8025.
  2. Xu, Z.; Meshcheryakov, V.A.; Poce, G.; Chng, S.S. MmpL3 is the flippase for mycolic acids in mycobacteria. Proc. Natl. Acad. Sci. USA 2017, 114, 7993–7998.
  3. Li, W.; Upadhyay, A.; Fontes, F.L.; North, E.J.; Wang, Y.; Crans, D.C.; Grzegorzewicz, A.E.; Jones, V.; Franzblau, S.G.; Lee, R.E.; et al. Novel insights into the mechanism of inhibition of MmpL3, a target of multiple pharmacophores in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 2014, 58, 6413–6423.
  4. World Health Organization. Global Tuberculosis Report 2019. Available online: (accessed on 7 January 2020).
  5. Lechartier, B.; Rybniker, J.; Zumla, A.; Cole, S.T. Tuberculosis drug discovery in the post-post-genomic era. EMBO Mol. Med. 2014, 6, 158–168.
  6. Chiarelli, L.R.; Mori, G.; Esposito, M.; Orena, B.S.; Pasca, M.R. New and old hot drug targets in tuberculosis. Curr. Med. Chem. 2016, 23, 3813–3846.
  7. Meneghetti, F.; Villa, S.; Gelain, A.; Barlocco, D.; Chiarelli, L.R.; Pasca, M.R.; Costantino, L. Iron acquisition pathways as targets for antitubercular drugs. Curr. Med. Chem. 2016, 23, 4009–4026.
  8. Mori, M.; Sammartino, J.C.; Costantino, L.; Gelain, A.; Meneghetti, F.; Villa, S.; Chiarelli, L.R. An Overview on the Potential Antimycobacterial Agents Targeting Serine/Threonine Protein Kinases from Mycobacterium tuberculosis. Curr. Top. Med. Chem. 2019, 19, 646–661.
  9. Andries, K.; Verhasselt, P.; Guillemont, J.; Göhlmann, H.W.; Neefs, J.M.; Winkler, H.; Van Gestel, J.; Timmerman, P.; Zhu, M.; Lee, E.; et al. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science 2005, 307, 223–227.
  10. Matsumoto, M.; Hashizume, H.; Tomishige, T.; Kawasaki, M.; Tsubouchi, H.; Sasaki, H.; Shimokawa, Y.; Komatsu, M. OPC-67683, a nitro-dihydro-imidazooxazole derivative with promising action against tuberculosis in vitro and in mice. PLoS Med. 2006, 3, e466.
  11. Stover, C.K.; Warrener, P.; VanDevanter, D.R.; Sherman, D.R.; Arain, T.M.; Langhorne, M.H.; Anderson, S.W.; Towell, J.A.; Yuan, Y.; McMurray, D.N.; et al. A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis. Nature 2000, 405, 962–966.
  12. Ryan, N.J.; Lo, J.H. Delamanid: First global approval. Drugs 2014, 74, 1041–1045.
  13. Keam, S.J. Pretomanid: First Approval. Drugs 2019, 79, 1797–1803.
  14. Cole, S.T. Inhibiting Mycobacterium tuberculosis within and without. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2016, 371, 20150506.
  15. Lee, B.S.; Pethe, K. Therapeutic potential of promiscuous targets in Mycobacterium tuberculosis. Curr. Opin. Pharmacol. 2018, 42, 22–26.
  16. Campaniço, A.; Moreira, R.; Lopes, F. Drug discovery in tuberculosis. New drug targets and antimycobacterial agents. Eur. J. Med. Chem. 2018, 150, 525–545.
  17. Makarov, V.; Manina, G.; Mikusova, K.; Möllmann, U.; Ryabova, O.; Saint-Joanis, B.; Dhar, N.; Pasca, M.R.; Buroni, S.; Lucarelli, A.P.; et al. Benzothiazinones kill Mycobacterium tuberculosis by blocking arabinan synthesis. Science 2009, 324, 801–804.
  18. Wolucka, B.A. Biosynthesis of D-arabinose in mycobacteria—A novel bacterial pathway with implications for antimycobacterial therapy. FEBS J. 2008, 275, 2691–2711.
  19. Christophe, T.; Jackson, M.; Jeon, H.K.; Fenistein, D.; Contreras-Dominguez, M.; Kim, J.; Genovesio, A.; Carralot, J.P.; Ewann, F.; Kim, E.H.; et al. High content screening identifies decaprenyl-phosphoribose 2′ epimerase as a target for intracellular antimycobacterial inhibitors. PLoS Pathog. 2009, 5, e1000645.
  20. Magnet, S.; Hartkoorn, R.C.; Székely, R.; Pató, J.; Triccas, J.A.; Schneider, P.; Szántai-Kis, C.; Orfi, L.; Chambon, M.; Banfi, D.; et al. Leads for antitubercular compounds from kinase inhibitor library screens. Tuberculosis 2010, 90, 354–360.
  21. La Rosa, V.; Poce, G.; Canseco, J.O.; Buroni, S.; Pasca, M.R.; Biava, M.; Raju, R.M.; Porretta, G.C.; Alfonso, S.; Battilocchio, C.; et al. MmpL3 is the cellular target of the antitubercular pyrrole derivative BM212. Antimicrob. Agents Chemother. 2012, 56, 324–331.
  22. Tahlan, K.; Wilson, R.; Kastrinsky, D.B.; Arora, K.; Nair, V.; Fischer, E.; Barnes, S.W.; Walker, J.R.; Alland, D.; Barry, C.E.; et al. SQ109 targets MmpL3, a membrane transporter of trehalose monomycolate involved in mycolic acid donation to the cell wall core of Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 2012, 56, 1797–1809.
  23. Grzegorzewicz, A.E.; Pham, H.; Gundi, V.A.; Scherman, M.S.; North, E.J.; Hess, T.; Jones, V.; Gruppo, V.; Born, S.E.; Korduláková, J.; et al. Inhibition of mycolic acid transport across the Mycobacterium tuberculosis plasma membrane. Nat. Chem. Biol. 2012, 8, 334–341.
  24. Riccardi, G.; Pasca, M.R.; Chiarelli, L.R.; Manina, G.; Mattevi, A.; Binda, C. The DprE1 enzyme, one of the most vulnerable targets of Mycobacterium tuberculosis. Appl. Microbiol. Biotechnol. 2013, 97, 8841–8848.
  25. Kolly, G.S.; Boldrin, F.; Sala, C.; Dhar, N.; Hartkoorn, R.C.; Ventura, M.; Serafini, A.; McKinney, J.D.; Manganelli, R.; Cole, S.T. Assessing the essentiality of the decaprenyl-phospho-d-arabinofuranose pathway in Mycobacterium tuberculosis using conditional mutants. Mol. Microbiol. 2014, 92, 194–211.
  26. Chikhale, R.V.; Barmade, M.A.; Murumkar, P.R.; Yadav, M.R. Overview of the development of dpre1 inhibitors for combating the menace of tuberculosis. J. Med. Chem. 2018, 61, 8563–8593.
  27. Makarov, V.; Lechartier, B.; Zhang, M.; Neres, J.; van der Sar, A.M.; Raadsen, S.A.; Hartkoorn, R.C.; Ryabova, O.B.; Vocat, A.; Decosterd, L.A.; et al. Towards a new combination therapy for tuberculosis with next generation benzothiazinones. EMBO Mol. Med. 2014, 6, 372–383.
  28. Available online: (accessed on 4 December 2019).
  29. Batt, S.M.; Cacho Izquierdo, M.; Castro Pichel, J.; Stubbs, C.J.; Del Peral, L.V.-G.; Pérez-Herrán, E.; Dhar, N.; Mouzon, B.; Rees, M.; Hutchinson, J.P.; et al. Whole cell target engagement identifies novel inhibitors of Mycobacterium tuberculosis decaprenylphosphoryl-β-d-ribose oxidase. ACS Infect. Dis 2015, 1, 615–626.
  30. Neres, J.; Hartkoorn, R.C.; Chiarelli, L.R.; Gadupudi, R.; Pasca, M.R.; Mori, G.; Venturelli, A.; Savina, S.; Makarov, V.; Kolly, G.S.; et al. 2-carboxyquinoxalines kill Mycobacterium tuberculosis through noncovalent inhibition of DprE1. ACS Chem. Biol. 2015, 10, 705–714.
  31. Naik, M.; Humnabadkar, V.; Tantry, S.J.; Panda, M.; Narayan, A.; Guptha, S.; Panduga, V.; Manjrekar, P.; Jena, L.K.; Koushik, K.; et al. 4-Aminoquinolone piperidine amides: Noncovalent inhibitors of DprE1 with long residence time and potent antimycobacterial activity. J. Med. Chem. 2014, 57, 5419–5434.
  32. Panda, M.; Ramachandran, S.; Ramachandran, V.; Shirude, P.S.; Humnabadkar, V.; Nagalapur, K.; Sharma, S.; Kaur, P.; Guptha, S.; Narayan, A.; et al. Discovery of pyrazolopyridones as a novel class of noncovalent DprE1 inhibitor with potent anti-mycobacterial activity. J. Med. Chem. 2014, 57, 4761–4771.
  33. Shirude, P.S.; Shandil, R.; Sadler, C.; Naik, M.; Hosagrahara, V.; Hameed, S.; Shinde, V.; Bathula, C.; Humnabadkar, V.; Kumar, N.; et al. Azaindoles: Noncovalent DprE1 inhibitors from scaffold morphing efforts, kill Mycobacterium tuberculosis and are efficacious in vivo. J. Med. Chem. 2013, 56, 9701–9708.
  34. Shirude, P.S.; Shandil, R.K.; Manjunatha, M.R.; Sadler, C.; Panda, M.; Panduga, V.; Reddy, J.; Saralaya, R.; Nanduri, R.; Ambady, A.; et al. Lead optimization of 1,4-azaindoles as antimycobacterial agents. J. Med. Chem. 2014, 57, 5728–5737.
  35. Available online: (accessed on 4 December 2019).
  36. Camacho, L.R.; Constant, P.; Raynaud, C.; Laneelle, M.A.; Triccas, J.A.; Gicquel, B.; Daffe, M.; Guilhot, C. Analysis of the phthiocerol dimycocerosate locus of Mycobacterium tuberculosis. Evidence that this lipid is involved in the cell wall permeability barrier. J. Biol. Chem. 2001, 276, 19845–19854.
  37. Converse, S.E.; Mougous, J.D.; Leavell, M.D.; Leary, J.A.; Bertozzi, C.R.; Cox, J.S. MmpL8 is required for sulfolipid-1 biosynthesis and Mycobacterium tuberculosis virulence. Proc. Natl. Acad. Sci. USA 2003, 100, 6121–6126.
  38. Pacheco, S.A.; Hsu, F.F.; Powers, K.M.; Purdy, G.E. MmpL11 protein transports mycolic acid-containing lipids to the mycobacterial cell wall and contributes to biofilm formation in Mycobacterium smegmatis. J. Biol. Chem. 2013, 288, 24213–24222.
  39. Wells, R.M.; Jones, C.M.; Xi, Z.; Speer, A.; Danilchanka, O.; Doornbos, K.S.; Sun, P.; Wu, F.; Tian, C.; Niederweis, M. Discovery of a siderophore export system essential for virulence of Mycobacterium tuberculosis. PLoS Pathog. 2013, 9, e1003120.
  40. Belardinelli, J.M.; Larrouy-Maumus, G.; Jones, V.; de Carvalho, L.P.S.; McNeil, M.R.; Jackson, M. Biosynthesis and translocation of unsulfated acyltrehaloses in Mycobacterium tuberculosis. J. Biol. Chem. 2014, 289, 27952–27965.
  41. Domenech, P.; Reed, M.B.; Barry, C.E. Contribution of the Mycobacterium tuberculosis MmpL protein family to virulence and drug resistance. Infect. Immun. 2005, 73, 3492–3501.
  42. Li, W.; Obregón-Henao, A.; Wallach, J.B.; North, E.J.; Lee, R.E.; Gonzalez-Juarrero, M.; Schnappinger, D.; Jackson, M. Therapeutic potential of the Mycobacterium tuberculosis mycolic acid transporter, MmpL3. Antimicrob. Agents Chemother. 2016, 60, 5198–5207.
  43. Stanley, S.A.; Grant, S.S.; Kawate, T.; Iwase, N.; Shimizu, M.; Wivagg, C.; Silvis, M.; Kazyanskaya, E.; Aquadro, J.; Golas, A.; et al. Identification of novel inhibitors of M. tuberculosis growth using whole cell based high-throughput screening. ACS Chem. Biol. 2012, 7, 1377–1384.
  44. Rao, S.P.; Lakshminarayana, S.B.; Kondreddi, R.R.; Herve, M.; Camacho, L.R.; Bifani, P.; Kalapala, S.K.; Jiricek, J.; Ma, N.L.; Tan, B.H.; et al. Indolcarboxamide is a preclinical candidate for treating multidrug-resistant tuberculosis. Sci. Transl. Med. 2013, 5, 214ra168.
  45. Remuiñán, M.J.; Pérez-Herrán, E.; Rullás, J.; Alemparte, C.; Martínez-Hoyos, M.; Dow, D.J.; Afari, J.; Mehta, N.; Esquivias, J.; Jiménez, E.; et al. Tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide and N-benzyl-6′,7′-dihydrospiro[piperidine-4,4′-thieno[3,2-c]pyran] analogues with bactericidal efficacy against Mycobacterium tuberculosis targeting MmpL3. PLoS ONE 2013, 8, e60933.
  46. Dupont, C.; Viljoen, A.; Dubar, F.; Blaise, M.; Bernut, A.; Pawlik, A.; Bouchier, C.; Brosch, R.; Guérardel, Y.; Lelièvre, J.; et al. A new piperidinol derivative targeting mycolic acid transport in Mycobacterium abscessus. Mol. Microbiol. 2016, 101, 515–529.
  47. Shetty, A.; Xu, Z.; Lakshmanan, U.; Hill, J.; Choong, M.L.; Chng, S.S.; Yamada, Y.; Poulsen, A.; Dick, T.; Gengenbacher, M. Novel acetamide indirectly targets mycobacterial transporter MmpL3 by proton motive force disruption. Front. Microbiol. 2018, 9, 2960.
  48. Zheng, H.; Williams, J.T.; Coulson, G.B.; Haiderer, E.R.; Abramovitch, R.B. HC2091 Kills Mycobacterium tuberculosis by targeting the MmpL3 mycolic acid transporter. Antimicrob. Agents Chemother. 2018, 62, e02459-17.
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