A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria

Science Translational Medicine

Volumn 7, Issue 296, 2015, Pages

  Phillips, Margaret A ^a   Lotharius, Julie ^b   Marsh, Kennan ^c   White, John ^d   Dayan, Anthony ^b   White, Karen L ^e   Njoroge, Jacqueline W ^a   El Mazouni, Farah ^a   Lao, Yanbin ^c   Kokkonda, Sreekanth ^d   Tomchick, Diana R ^f   Deng, Xiaoyi ^a   Laird, Trevor ^b   Bhatia, Sangeeta N ^g   March, Sandra ^g   Ng, Caroline L ^h   Fidock, David A ^h   Wittlin, Sergio ^i,j   Lafuente Monasterio, Maria ^k   Benito, Francisco Javier Gamo ^k   Alonso, Laura Maria Sanz ^k   Martinez, Maria Santos ^k   Jimenez Diaz, Maria Belen ^k   Bazaga, Santiago Ferrer ^k   Angulo Barturen, Iñigo ^k   Haselden, John N ^k   Louttit, James ^l   Cui, Yi ^l   Sridhar, Arun ^l   Zeeman, Anna Marie ^m   Kocken, Clemens ^m   Sauerwein, Robert ⁿ   Dechering, Koen ⁿ   Avery, Vicky M ^o   Duffy, Sandra ^o   Delves, Michael ^p   Sinden, Robert ^p   Ruecker, Andrea ^p   Wickham, Kristina S ^q   Rochford, Rosemary ^q   Gahagen, Janet ^r   Iyer, Lalitha ^r   Riccio, Ed ^r   Mirsalis, Jon ^r   Bathhurst, Ian ^b   Rueckle, Thomas ^b   Ding, Xavier ^b   Campo, Brice ^b   Leroy, Didier ^b   Rogers, M John ^s   Rathod, Pradipsinh K ^d   Burrows, Jeremy N ^b   Charman, Susan A ^e   more..

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b Medicines for Malaria Venture   (Switzerland)

^c ABBVIE INC   (United States)

^d UNIVERSITY OF WASHINGTON   (United States)

^e MONASH UNIVERSITY   (Australia)

^f UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^g MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^h Department of Medicine   (United States)

ⁱ SWISS TROPICAL AND PUBLIC HEALTH INSTITUTE   (Switzerland)

^j UNIVERSITY OF BASEL   (Switzerland)

^k GLAXOSMITHKLINE   (Spain)

^l GLAXOSMITHKLINE   (United Kingdom)

^m BIOMEDICAL PRIMATE RESEARCH CENTRE   (Netherlands)

ⁿ Current affiliation: TropIQ Health Sciences   (Netherlands)

^o GRIFFITH UNIVERSITY   (Australia)

^p IMPERIAL COLLEGE LONDON   (United Kingdom)

^q SUNY UPSTATE MEDICAL UNIVERSITY   (United States)

^r SRI INTERNATIONAL   (United States)

^s National Institute for Allergy and Infectious Disease   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ANTIMALARIAL AGENT; DIHYDROOROTATE DEHYDROGENASE INHIBITOR; DRUG METABOLITE; DSM 265; UNCLASSIFIED DRUG; DIHYDROOROTATE DEHYDROGENASE; DSM265; ENZYME INHIBITOR; OXIDOREDUCTASE; PYRIMIDINE DERIVATIVE; TRIAZOLE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIMALARIAL ACTIVITY; ARTICLE; CARDIOVASCULAR RISK; DRUG ABSORPTION; DRUG BINDING; DRUG BLOOD LEVEL; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG EXCRETION; DRUG HALF LIFE; DRUG METABOLISM; DRUG POTENTIATION; DRUG RESISTANCE; DRUG SAFETY; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG TOLERABILITY; FEMALE; GENOTOXICITY; MALARIA; MALARIA CONTROL; MALARIA FALCIPARUM; MALE; MOUSE; NONHUMAN; PARASITE ISOLATION; PLASMODIUM; PRIORITY JOURNAL; RAT; ANIMAL; ANTAGONISTS AND INHIBITORS; AREA UNDER THE CURVE; CACO-2 CELL LINE; CHEMISTRY; DOG; ENZYME SPECIFICITY; HAPLORHINI; HUMAN; IC50; MALARIA, FALCIPARUM; MOLECULAR GENETICS; NONOBESE DIABETIC MOUSE; ORAL DRUG ADMINISTRATION; PLASMODIUM FALCIPARUM; PRECLINICAL STUDY; RABBIT; SCID MOUSE; X RAY CRYSTALLOGRAPHY;

ADMINISTRATION, ORAL; ANIMALS; ANTIMALARIALS; AREA UNDER CURVE; CACO-2 CELLS; CRYSTALLOGRAPHY, X-RAY; DOGS; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; HAPLORHINI; HUMANS; INHIBITORY CONCENTRATION 50; MALARIA, FALCIPARUM; MICE; MICE, INBRED NOD; MICE, SCID; MOLECULAR SEQUENCE DATA; OXIDOREDUCTASES ACTING ON CH-CH GROUP DONORS; PLASMODIUM FALCIPARUM; PYRIMIDINES; RABBITS; SUBSTRATE SPECIFICITY; TRIAZOLES;

EID: 84937141039     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.aaa6645     Document Type: Article

References (66)

1. N. J. White, S. Pukrittayakamee, T. T. Hien, M. A. Faiz, O. A. Mokuolu, A. M. Dondorp, Malaria. Lancet 383, 723-735 (2014).
2. L. H. Miller, H. C. Ackerman, X. Z. Su, T. E. Wellems, Malaria biology and disease pathogenesis: Insights for new treatments. Nat. Med. 19, 156-167 (2013).
3. World Malaria Report (World Health Organization, Geneva, 2014); www.who.int/malaria/publications/world-malaria-report-2014/en.
4. C. Cotter, H. J. Sturrock, M. S. Hsiang, J. Liu, A. A. Phillips, J. Hwang, C. S. Gueye, N. Fullman, R. D. Gosling, R. G. Feachem, The changing epidemiology of malaria elimination: New strategies for new challenges. Lancet 382, 900-911 (2013).
5. J. N. Burrows, E. Burlot, B. Campo, S. Cherbuin, S. Jeanneret, D. Leroy, T. Spangenberg, D. Waterson, T. N. Wells, P. Willis, Antimalarial drug discovery-The path towards eradication. Parasitology 141, 128-139 (2014).
6. R. N. Price, F. Nosten, Single-dose radical cure of Plasmodium vivax: A step closer. Lancet 383, 1020-1021 (2014).
7. D. Menard, F. Ariey, Towards real-time monitoring of artemisinin resistance. Lancet Infect. Dis. 15, 367-368 (2015).
8. M. P. Anthony, J. N. Burrows, S. Duparc, J. J. Moehrle, T. N. Wells, The global pipeline of new medicines for the control and elimination of malaria. Malar. J. 11, 316 (2012).
9. Y. Yuthavong, B. Tarnchompoo, T. Vilaivan, P. Chitnumsub, S. Kamchonwongpaisan, S. A. Charman, D. N. McLennan, K. L. White, L. Vivas, E. Bongard, C. Thongphanchang, S. Taweechai, J. Vanichtanankul, R. Rattanajak, U. Arwon, P. Fantauzzi, J. Yuvaniyama, W. N. Charman, D. Matthews, Malarial dihydrofolate reductase as a paradigm for drug development against a resistance-compromised target. Proc. Natl. Acad. Sci. U.S.A. 109, 16823-16828 (2012).
10. S. Duparc, C. Lanza, D. Ubben, I. Borghini-Fuhrer, L. Kellam, Optimal dose finding for novel antimalarial combination therapy. Trop. Med. Int. Health 17, 409-413 (2012).
11. J. N. Burrows, R. H. van Huijsduijnen, J. J. Möhrle, C. Oeuvray, T. N. Wells, Designing the next generation of medicines for malaria control and eradication. Malar. J. 12, 187 (2013).
12. P. A. Stocks, V. Barton, T. Antoine, G. A. Biagini, S. A. Ward, P. M. O'Neill, Novel inhibitors of the Plasmodium falciparum electron transport chain. Parasitology 141, 50-65 (2014).
13. M. A. Phillips, P. K. Rathod, Plasmodium dihydroorotate dehydrogenase: A promising target for novel anti-malarial chemotherapy. Infect. Disord. Drug Targets 10, 226-239 (2010).
14. J. M. Coteron, M. Marco, J. Esquivias, X. Deng, K. L. White, J. White, M. Koltun, F. El Mazouni, S. Kokkonda, K. Katneni, R. Bhamidipati, D. M. Shackleford, I. Angulo-Barturen, S. B. Ferrer, M. B. Jiménéz-Díaz, F. J. Gamo, E. J. Goldsmith, W. N. Charman, I. Bathurst, D. Floyd, D. Matthews, J. N. Burrows, P. K. Rathod, S. A. Charman, M. A. Phillips, Structure-guided lead optimization of triazolopyrimidine-ring substituents identifies potent Plasmodium falciparum dihydroorotate dehydrogenase inhibitors with clinical candidate potential. J. Med. Chem. 54, 5540-5561 (2011).
15. R. Gujjar, F. El Mazouni, K. L. White, J. White, S. Creason, D. M. Shackleford, X. Deng, W. N. Charman, I. Bathurst, J. Burrows, D. M. Floyd, D. Matthews, F. S. Buckner, S. A. Charman, M. A. Phillips, P. K. Rathod, Lead optimization of aryl and aralkyl amine based triazolopyrimidine inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase with anti-malarial activity in mice. J. Med. Chem. 54, 3935-3949 (2011).
16. X. Deng, S. Kokkonda, F. El Mazouni, J. White, J. N. Burrows, W. Kaminsky, S. A. Charman, D. Matthews, P. K. Rathod, M. A. Phillips, Fluorine modulates species selectivity in the triazolopyrimidine class of Plasmodium falciparum dihydroorotate dehydrogenase inhibitors. J. Med. Chem. 57, 5381-5394 (2014).
17. M. Delves, D. Plouffe, C. Scheurer, S. Meister, S. Wittlin, E. A. Winzeler, R. E. Sinden, D. Leroy, The activities of current antimalarial drugs on the life cycle stages of Plasmodium: A comparative study with human and rodent parasites. PLOS Med. 9, e1001169 (2012).
18. X. C. Ding, D. Ubben, T. N. Wells, A framework for assessing the risk of resistance for anti-malarials in development. Malar. J. 11, 292 (2012).
19. P. J. Kannankeril, D. M. Roden, When should QT be measured? Summer solstice or Christmas Eve? Heart Rhythm 4, 282-283 (2007).
20. T. Liu, B. S. Brown, Y. Wu, C. Antzelevitch, P. R. Kowey, G. X. Yan, Blinded validation of the isolated arterially perfused rabbit ventricular wedge in preclinical assessment of drug-induced proarrhythmias. Heart Rhythm 3, 948-956 (2006).
21. av rather than AUC in safety assessment. Regul. Toxicol. Pharmacol. 57,70-73 (2010).
22. K. L. Kuhen, A. K. Chatterjee, M. Rottmann, K. Gagaring, R. Borboa, J. Buenviaje, Z. Chen, C. Francek, T.Wu,A.Nagle,S.W.Barnes,D.Plouffe,M.C.Lee,D.A.Fidock,W.Graumans,M.vandeVegte-Bolmer, G. J. van Gemert, G. Wirjanata, B. Sebayang, J. Marfurt, B. Russell, R. Suwanarusk, R. N. Price, F. Nosten, A. Tungtaeng, M. Gettayacamin, J. Sattabongkot, J. Taylor, J. R. Walker, D. Tully, K. P. Patra, E. L. Flannery, J. M. Vinetz, L. Renia, R. W. Sauerwein, E. A. Winzeler, R. J. Glynne, T. T. Diagana, KAF156 is an antimalarial clinical candidate with potential for use in prophylaxis, treatment, and prevention of disease transmission. Antimicrob. Agents Chemother. 58, 5060-5067 (2014).
23. F. J. Leong, R. Zhao, S. Zeng, B. Magnusson, T. T. Diagana, P. Pertel, A first-in-human randomized, double-blind, placebo-controlled, single- and multiple-ascending oral dose study of novel imidazolopiperazine KAF156 to assess its safety, tolerability, and pharmacokinetics in healthy adult volunteers. Antimicrob. Agents Chemother. 58, 6437-6443 (2014).
24. B.Baragaña,I.Hallyburton,M.C.Lee,N.R.Norcross,R.Grimaldi,T.D.Otto,W.R.Proto, A. M. Blagborough, S. Meister, G. Wirjanata, A. Ruecker, L. M. Upton, T. S. Abraham, M. J. Almeida, A. Pradhan, A. Porzelle, M. S. Martínez, J. M. Bolscher, A. Woodland, S. Norval, F. Zuccotto, J. Thomas, F. Simeons, L. Stojanovski, M. Osuna-Cabello, P. M. Brock, T. S. Churcher, K. A. Sala, S. E. Zakutansky, M. B. Jiménez-Díaz, L. M. Sanz, J. Riley, R. Basak, M. Campbell, V. M. Avery, R. W. Sauerwein, K. J. Dechering, R. Noviyanti, B. Campo, J. A. Frearson, I. Angulo-Barturen, S. Ferrer-Bazaga, F.J.Gamo,P.G.Wyatt,D.Leroy,P.Siegl,M.J.Delves,D.E.Kyle,S.Wittlin,J.Marfurt,R.N.Price, R. E. Sinden, E. A. Winzeler, S. A. Charman, L. Bebrevska, D. W. Gray, S. Campbell, A. H. Fairlamb, P. A. Willis, J. C. Rayner, D. A. Fidock, K. D. Read, I. H. Gilbert, A novel multiple-stage antimalarial agent that inhibits protein synthesis. Nature 522, 315-320 (2015).
25. A. Nilsen, A. N. LaCrue, K. L. White, I. P. Forquer, R. M. Cross, J. Marfurt, M. W. Mather, M. J. Delves, D. M. Shackleford, F. E. Saenz, J. M. Morrisey, J. Steuten, T. Mutka, Y. Li, G. Wirjanata, E. Ryan, S. Duffy, J. X. Kelly, B. F. Sebayang, A. M. Zeeman, R. Noviyanti, R. E. Sinden, C. H. Kocken, R. N. Price, V. M. Avery, I. Angulo-Barturen, M. B. Jiménez-Díaz, S. Ferrer, E. Herreros, L. M. Sanz, F. J. Gamo, I. Bathurst, J. N. Burrows, P. Siegl, R. K. Guy, R. W. Winter, A. B. Vaidya, S. A. Charman, D. E. Kyle, R. Manetsch, M. K. Riscoe, Quinolone-3-diarylethers: A new class of antimalarial drug. Sci. Transl. Med. 5, 177ra137 (2013).
26. R.A.Cooper,M.T.Ferdig,X.Z.Su,L.M.Ursos,J.Mu,T.Nomura,H.Fujioka,D.A.Fidock, P. D. Roepe, T. E. Wellems, Alternative mutations at position 76 of the vacuolar transmembrane protein PfCRT are associated with chloroquine resistance and unique stereospecific quinine and quinidine responses in Plasmodium falciparum. Mol. Pharmacol. 61,35-42 (2002).
27. N. J. White, S. Pukrittayakamee, A. P. Phyo, R. Rueangweerayut, F. Nosten, P. Jittamala, A. Jeeyapant, J. P. Jain, G. Lefèvre, R. Li, B. Magnusson, T. T. Diagana, F. J. Leong, Spiroindolone KAE609 for falciparum and vivax malaria. N. Engl. J. Med. 371,403-410 (2014).
28. M. B. Jiménez-Díaz, D. Ebert, Y. Salinas, A. Pradhan, A. M. Lehane, M. E. Myrand-Lapierre, K. G. O'Loughlin, D. M. Shackleford, M. Justino de Almeida, A. K. Carrillo, J. A. Clark, A. S. Dennis, J. Diep, X. Deng, S. Duffy, A. N. Endsley, G. Fedewa, W. A. Guiguemde, M. G. Gómez, G. Holbrook, J. Horst, C. C. Kim, J. Liu, M. C. Lee, A. Matheny, M. S. Martínez, G. Miller, A. Rodríguez-Alejandre, L. Sanz, M. Sigal, N. J. Spillman, P. D. Stein, Z. Wang, F. Zhu, D. Waterson, S. Knapp, A. Shelat, V.M.Avery,D.A.Fidock,F.J.Gamo,S.A.Charman,J.C.Mirsalis,H.Ma,S.Ferrer,K.Kirk, I. Angulo-Barturen, D. E. Kyle, J. L. DeRisi, D. M. Floyd, R. K. Guy, (+)-SJ733, a clinical candidate for malaria that acts through ATP4 to induce rapid host-mediated clearance of Plasmodium. Proc. Natl. Acad. Sci. U.S.A. 111, E5455-E5462 (2014).
29. J. L. Guler, D. L. Freeman, V. Ahyong, R. Patrapuvich, J. White, R. Gujjar, M. A. Phillips, J. DeRisi, P. K. Rathod, Asexual populations of the human malaria parasite, Plasmodium falciparum, use a two-step genomic strategy to acquire accurate, beneficial DNA amplifications. PLOS Pathog. 9, e1003375 (2013).
30. L. S. Ross, F. J. Gamo, M. J. Lafuente-Monasterio, O. M. Singh, P. Rowland, R. C. Wiegand, D. F. Wirth, In vitro resistance selections for Plasmodium falciparum dihydroorotate dehydrogenase inhibitors give mutants with multiple point mutations in the drug-binding site and altered growth. J. Biol. Chem. 289, 17980-17995 (2014).
31. H. I. Keen, P. G. Conaghan, S. E. Tett, Safety evaluation of leflunomide in rheumatoid arthritis. Expert Opin. Drug Saf. 12, 581-588 (2013).
32. Leflunomide FDA Drug Approval Package: NDA 20905 (U.S. Food and Drug Administration, Baltimore, MD, 1998); www.accessdata.fda.gov/drugsatfda-docs/nda/98/20905-arava.cfm.
33. L. M. Sanz, B. Crespo, C. De-Cózar, X. C. Ding, J. L. Llergo, J. N. Burrows, J. F. Garciá-Bustos, F. J. Gamo, P. falciparum in vitro killing rates allow to discriminate between different antimalarial mode-of-action. PLOS One 7, e30949 (2012).
34. S. March, S. Ng, S. Velmurugan, A. Galstian, J. Shan, D. J. Logan, A. E. Carpenter, D. Thomas, B. K. Sim, M. M. Mota, S. L. Hoffman, S. N. Bhatia, A microscale human liver platform that supports the hepatic stages of Plasmodium falciparum and vivax. Cell Host Microbe 14, 104-115 (2013).
35. E. H. Ekland, J. Schneider, D. A. Fidock, Identifying apicoplast-targeting antimalarials using high-throughput compatible approaches. FASEB J. 25, 3583-3593 (2011).
36. nullmice engrafted with human erythrocytes. Antimicrob. Agents Chemother. 53, 4533-4536 (2009).
37. R. Rochford, C. Ohrt, P. C. Baresel, B. Campo, A. Sampath, A. J. Magill, B. L. Tekwani, L. A. Walker, Humanized mouse model of glucose 6-phosphate dehydrogenase deficiency for in vivo assessment of hemolytic toxicity. Proc. Natl. Acad. Sci. U.S.A. 110, 17486-17491 (2013).
38. J. Baldwin, C. H. Michnoff, N. A. Malmquist, J. White, M. G. Roth, P. K. Rathod, M. A. Phillips, High-throughput screening for potent and selective inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase. J. Biol. Chem. 280, 21847-21853 (2005).
39. N. A. Malmquist, R. Gujjar, P. K. Rathod, M. A. Phillips, Analysis of flavin oxidation and electrontransfer inhibition in Plasmodium falciparum dihydroorotate dehydrogenase. Biochemistry 47, 2466-2475 (2008).
40. M. A. Phillips, R. Gujjar, N. A. Malmquist, J. White, F. El Mazouni, J. Baldwin, P. K. Rathod, Triazolopyrimidine-based dihydroorotate dehydrogenase inhibitors with potent and selective activity against the malaria parasite, Plasmodium falciparum. J. Med. Chem. 51, 3649-3653 (2008).
41. X. Deng, R. Gujjar, F. El Mazouni, W. Kaminsky, N. A. Malmquist, E. J. Goldsmith, P. K. Rathod, M. A. Phillips, Structural plasticity of malaria dihydroorotate dehydrogenase allows selective binding of diverse chemical scaffolds. J. Biol. Chem. 284, 26999-27009 (2009).
42. Z. Otwinowski, W. Minor, C. W. Carter Jr., Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307-326 (1997).
43. P. R. Evans, An introduction to data reduction: Space-group determination, scaling and intensity statistics. Acta Crystallogr. D Biol. Crystallogr. 67, 282-292 (2011).
44. A. J. McCoy, Solving structures of protein complexes by molecular replacement with Phaser. Acta Crystallogr. D Biol. Crystallogr. 63, 32-41 (2007).
45. P. D. Adams, P. V. Afonine, G. Bunkóczi, V. B. Chen, I. W. Davis, N. Echols, J. J. Headd, L. W. Hung, G.J.Kapral,R.W.Grosse-Kunstleve,A.J.McCoy,N.W.Moriarty,R.Oeffner,R.J.Read,D.C.Richardson, J. S. Richardson, T. C. Terwilliger, P. H. Zwart, PHENIX: A comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66, 213-221 (2010).
46. P. Emsley, B. Lohkamp, W. G. Scott, K. Cowtan, Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66, 486-501 (2010).
47. L. Dembele, A. Gego, A. M. Zeeman, J. F. Franetich, O. Silvie, A. Rametti, R. Le Grand, N. Dereuddre-Bosquet, R. Sauerwein, G. J. van Gemert, J. C. Vaillant, A. W. Thomas, G. Snounou, C. H. Kocken, D. Mazier, Towards an in vitro model of Plasmodium hypnozoites suitable for drug discovery. PLOS One 6, e18162 (2011).
48. A. M. Zeeman, S. M. van Amsterdam, C. W. McNamara, A. Voorberg-van der Wel, E. J. Klooster, A. van den Berg, E. J. Remarque, D. M. Plouffe, G. J. van Gemert, A. Luty, R. Sauerwein, K. Gagaring, R. Borboa, Z. Chen, K. Kuhen, R. J. Glynne, A. K. Chatterjee, A. Nagle, J. Roland, E. A. Winzeler, D. Leroy, B. Campo, T. T. Diagana, B. K. Yeung, A. W. Thomas, C. H. Kocken, KAI407, a potent non-8-aminoquinoline compound that kills Plasmodium cynomolgi early dormant liver stage parasites in vitro. Antimicrob. Agents Chemother. 58, 1586-1595 (2014).
49. S. D'Alessandro, F. Silvestrini, K. Dechering, Y. Corbett, S. Parapini, M. Timmerman, L. Galastri, N. Basilico, R. Sauerwein, P. Alano, D. Taramelli, A Plasmodium falciparum screening assay for anti-gametocyte drugs based on parasite lactate dehydrogenase detection. J. Antimicrob. Chemother. 68, 2048-2058 (2013).
50. S. Duffy, V. M. Avery, Identification of inhibitors of Plasmodium falciparum gametocyte development. Malar. J. 12, 408 (2013).
51. M. J. Delves, C. Ramakrishnan, A. M. Blagborough, D. Leroy, T. N. Wells, R. E. Sinden, A highthroughput assay for the identification of malarial transmission-blocking drugs and vaccines. Int. J. Parasitol. 42, 999-1006 (2012).
52. M. J. Delves, A. Ruecker, U. Straschil, J. Lelièvre, S. Marques, M. J. López-Barragán, E. Herreros, R. E. Sinden, Male and female Plasmodium falciparum mature gametocytes show different responses to antimalarial drugs. Antimicrob. Agents Chemother. 57, 3268-3274 (2013).
53. C. Snyder, J. Chollet, J. Santo-Tomas, C. Scheurer, S. Wittlin, In vitro and in vivo interaction of synthetic peroxide RBx11160 (OZ277) with piperaquine in Plasmodium models. Exp. Parasitol. 115, 296-300 (2007).
54. Q. L. Fivelman, I. S. Adagu, D. C. Warhurst, Modified fixed-ratio isobologram method for studying in vitro interactions between atovaquone and proguanil or dihydroartemisinin against drug-resistant strains of Plasmodium falciparum. Antimicrob. Agents Chemother. 48, 4097-4102 (2004).
55. S. Schleiferböck, C. Scheurer, M. Ihara, I. Itoh, I. Bathurst, J. N. Burrows, P. Fantauzzi, J. Lotharius, S. A. Charman, J. Morizzi, D. M. Shackleford, K. L. White, R. Brun, S. Wittlin, In vitro and in vivo characterization of the antimalarial lead compound SSJ-183 in Plasmodium models. Drug Des. Devel. Ther. 7, 1377-1384 (2013).
56. E. Jantratid, N. Janssen, C. Reppas, J. B. Dressman, Dissolution media simulating conditions in the proximal human gastrointestinal tract: An update. Pharm. Res. 25, 1663-1676 (2008).
57. D. M. Roden, P. Kannankeril, D. Darbar, On the relationship among QT interval, atrial fibrillation, and torsade de pointes. Europace 9, iv1-iv3 (2007).
58. H. R. Lu, E. Vlaminckx, A. Van de Water, J. Rohrbacher, A. Hermans, D. J. Gallacher, In-vitro experimental models for the risk assessment of antibiotic-induced QT prolongation. Eur. J. Pharmacol. 577, 222-232 (2007).
59. K. Mortelmans, E. Zeiger, The Ames Salmonella/microsome mutagenicity assay. Mutat. Res. 455, 29-60 (2000).
60. K. Mortelmans, E. S. Riccio, The bacterial tryptophan reverse mutation assay with Escherichia coli WP2. Mutat. Res. 455, 61-69 (2000).
61. S. Deferme, R. Mols, W. Van Driessche, P. Augustijns, Apricot extract inhibits the P-gp-mediated efflux of talinolol. J. Pharm. Sci. 91, 2539-2548 (2002).
62. Q. Mao, J. D. Unadkat, Role of the breast cancer resistance protein (ABCG2) in drug transport. AAPS J. 7, E118-E133 (2005).
63. Y. H. Zhao, J. Le, M. H. Abraham, A. Hersey, P. J. Eddershaw, C. N. Luscombe, D. Butina, G. Beck, B. Sherborne, I. Cooper, J. A. Platts, Evaluation of human intestinal absorption data and subsequent derivation of a quantitative structure-activity relationship (QSAR) with the Abraham descriptors. J. Pharm. Sci. 90, 749-784 (2001).
64. V. B. Chen, W. B. Arendall III, J. J. Headd, D. A. Keedy, R. M. Immormino, G. J. Kapral, L. W. Murray, J. S. Richardson, D. C. Richardson, MolProbity: All-atom structure validation for macromolecular crystallography. Acta Crystallogr. D Biol. Crystallogr. 66, 12-21 (2010).
65. J. L. Vennerstrom, S. Arbe-Barnes, R. Brun, S. A. Charman, F. C. Chiu, J. Chollet, Y. Dong, A. Dorn, D. Hunziker, H. Matile, K. McIntosh, M. Padmanilayam, J. Santo Tomas, C. Scheurer, B. Scorneaux, Y. Tang, H. Urwyler, S. Wittlin, W. N. Charman, Identification of an antimalarial synthetic trioxolane drug development candidate. Nature 430, 900-904 (2004).
66. R. L. Brent, The history of the editorship of Teratology during the period from July 1, 1976 to January 1, 1993. Teratology 63, 100-105 (2001).