3i7c › Citations

Toxoplasma gondii calcium-dependent protein kinase 1 is a target for selective kinase inhibitors.

Ojo KK, Larson ET, Keyloun KR, Castaneda LJ, Derocher AE, Inampudi KK, Kim JE, Arakaki TL, Murphy RC, Zhang L, Napuli AJ, Maly DJ, Verlinde CL, Buckner FS, Parsons M, Hol WG, Merritt EA, Van Voorhis WC
Nat Struct Mol Biol 17 602-7 (2010)
Related entries: 3i79, 3i7b, 3mwu, 3n51, 3ncg

Cited: 114 times
EuropePMC logo PMID: 20436472

Abstract

New drugs are needed to treat toxoplasmosis. Toxoplasma gondii calcium-dependent protein kinases (TgCDPKs) are attractive targets because they are absent in mammals. We show that TgCDPK1 is inhibited by low nanomolar levels of bumped kinase inhibitors (BKIs), compounds inactive against mammalian kinases. Cocrystal structures of TgCDPK1 with BKIs confirm that the structural basis for selectivity is due to the unique glycine gatekeeper residue in the ATP-binding site. We show that BKIs interfere with an early step in T. gondii infection of human cells in culture. Furthermore, we show that TgCDPK1 is the in vivo target of BKIs because T. gondii expressing a glycine to methionine gatekeeper mutant enzyme show significantly decreased sensitivity to BKIs. Thus, design of selective TgCDPK1 inhibitors with low host toxicity may be achievable.

Reviews - 3i7c mentioned but not cited (2)

  1. Designing selective inhibitors for calcium-dependent protein kinases in apicomplexans. Hui R, El Bakkouri M, Sibley LD. Trends Pharmacol Sci 36 452-460 (2015)
  2. The calcium-dependent protein kinase 1 from Toxoplasma gondii as target for structure-based drug design. Cardew EM, Verlinde CLMJ, Pohl E. Parasitology 145 210-218 (2018)

Articles - 3i7c mentioned but not cited (6)

  1. Toxoplasma gondii calcium-dependent protein kinase 1 is a target for selective kinase inhibitors. Ojo KK, Larson ET, Keyloun KR, Castaneda LJ, Derocher AE, Inampudi KK, Kim JE, Arakaki TL, Murphy RC, Zhang L, Napuli AJ, Maly DJ, Verlinde CL, Buckner FS, Parsons M, Hol WG, Merritt EA, Van Voorhis WC. Nat Struct Mol Biol 17 602-607 (2010)
  2. Potent and selective inhibitors of CDPK1 from T. gondii and C. parvum based on a 5-aminopyrazole-4-carboxamide scaffold. Zhang Z, Ojo KK, Vidadala R, Huang W, Geiger JA, Scheele S, Choi R, Reid MC, Keyloun KR, Rivas K, Siddaramaiah LK, Comess KM, Robinson KP, Merta PJ, Kifle L, Hol WG, Parsons M, Merritt EA, Maly DJ, Verlinde CL, Van Voorhis WC, Fan E. ACS Med Chem Lett 5 40-44 (2014)
  3. Genes associated with genotype-specific DNA methylation in squamous cell carcinoma as candidate drug targets. Kinoshita R, Iwadate M, Umeyama H, Taguchi YH. BMC Syst Biol 8 Suppl 1 S4 (2014)
  4. Structure-guided optimization of protein kinase inhibitors reverses aminoglycoside antibiotic resistance. Stogios PJ, Spanogiannopoulos P, Evdokimova E, Egorova O, Shakya T, Todorovic N, Capretta A, Wright GD, Savchenko A. Biochem J 454 191-200 (2013)
  5. Optimization of an imidazopyridazine series of inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1). Chapman TM, Osborne SA, Wallace C, Birchall K, Bouloc N, Jones HM, Ansell KH, Taylor DL, Clough B, Green JL, Holder AA. J Med Chem 57 3570-3587 (2014)
  6. A novel benzodioxole-containing inhibitor of Toxoplasma gondii growth alters the parasite cell cycle. Kamau E, Meehan T, Lavine MD, Arrizabalaga G, Mustata Wilson G, Boyle J. Antimicrob Agents Chemother 55 5438-5451 (2011)


Reviews citing this publication (25)

  1. Drugs in development for toxoplasmosis: advances, challenges, and current status. Alday PH, Doggett JS. Drug Des Devel Ther 11 273-293 (2017)
  2. Calcium and reactive oxygen species rule the waves of signaling. Steinhorst L, Kudla J. Plant Physiol 163 471-485 (2013)
  3. Ocular toxoplasmosis past, present and new aspects of an old disease. Maenz M, Schlüter D, Liesenfeld O, Schares G, Gross U, Pleyer U. Prog Retin Eye Res 39 77-106 (2014)
  4. The calcium signaling toolkit of the Apicomplexan parasites Toxoplasma gondii and Plasmodium spp. Lourido S, Moreno SN. Cell Calcium 57 186-193 (2015)
  5. Biochemical regulation of in vivo function of plant calcium-dependent protein kinases (CDPK). Liese A, Romeis T. Biochim Biophys Acta 1833 1582-1589 (2013)
  6. How apicomplexan parasites move in and out of cells. Sibley LD. Curr Opin Biotechnol 21 592-598 (2010)
  7. Toxoplasma and Plasmodium protein kinases: roles in invasion and host cell remodelling. Lim DC, Cooke BM, Doerig C, Saeij JP. Int J Parasitol 42 21-32 (2012)
  8. The kinomes of apicomplexan parasites. Miranda-Saavedra D, Gabaldón T, Barton GJ, Langsley G, Doerig C. Microbes Infect 14 796-810 (2012)
  9. New antibacterials for the treatment of toxoplasmosis; a patent review. Rodriguez JB, Szajnman SH. Expert Opin Ther Pat 22 311-333 (2012)
  10. Extended-spectrum antiprotozoal bumped kinase inhibitors: A review. Van Voorhis WC, Doggett JS, Parsons M, Hulverson MA, Choi R, Arnold SLM, Riggs MW, Hemphill A, Howe DK, Mealey RH, Lau AOT, Merritt EA, Maly DJ, Fan E, Ojo KK. Exp Parasitol 180 71-83 (2017)
  11. Drug Development Against the Major Diarrhea-Causing Parasites of the Small Intestine, Cryptosporidium and Giardia. Miyamoto Y, Eckmann L. Front Microbiol 6 1208 (2015)
  12. Protein kinases of Toxoplasma gondii: functions and drug targets. Wei F, Wang W, Liu Q. Parasitol Res 112 2121-2129 (2013)
  13. Drug target identification in protozoan parasites. Müller J, Hemphill A. Expert Opin Drug Discov 11 815-824 (2016)
  14. Calcium-dependent protein kinases are potential targets for Toxoplasma gondii vaccine. Foroutan M, Ghaffarifar F. Clin Exp Vaccine Res 7 24-36 (2018)
  15. Calcium signaling and the lytic cycle of the Apicomplexan parasite Toxoplasma gondii. Hortua Triana MA, Márquez-Nogueras KM, Vella SA, Moreno SNJ. Biochim Biophys Acta Mol Cell Res 1865 1846-1856 (2018)
  16. Therapy for ocular toxoplasmosis--the future. Garweg JG, Stanford MR. Ocul Immunol Inflamm 21 300-305 (2013)
  17. Emerging treatment options for cryptosporidiosis. Love MS, Choy RKM. Curr Opin Infect Dis 34 455-462 (2021)
  18. One health therapeutics: Target-Based drug development for cryptosporidiosis and other apicomplexa diseases. Van Voorhis WC, Hulverson MA, Choi R, Huang W, Arnold SLM, Schaefer DA, Betzer DP, Vidadala RSR, Lee S, Whitman GR, Barrett LK, Maly DJ, Riggs MW, Fan E, Kennedy TJ, Tzipori S, Doggett JS, Winzer P, Anghel N, Imhof D, Müller J, Hemphill A, Ferre I, Sanchez-Sanchez R, Ortega-Mora LM, Ojo KK. Vet Parasitol 289 109336 (2021)
  19. Promising Drug Targets and Compounds with Anti-Toxoplasma gondii Activity. Silva MD, Teixeira C, Gomes P, Borges M. Microorganisms 9 1960 (2021)
  20. Screening for small molecule inhibitors of Toxoplasma gondii. Kortagere S. Expert Opin Drug Discov 7 1193-1206 (2012)
  21. Toxoplasmosis: Current and Emerging Parasite Druggable Targets. Hajj RE, Tawk L, Itani S, Hamie M, Ezzeddine J, El Sabban M, El Hajj H. Microorganisms 9 2531 (2021)
  22. Roles of Apicomplexan protein kinases at each life cycle stage. Kato K, Sugi T, Iwanaga T. Parasitol Int 61 224-234 (2012)
  23. Three-dimensional structures in the design of therapeutics targeting parasitic protozoa: reflections on the past, present and future. Hol WG. Acta Crystallogr F Struct Biol Commun 71 485-499 (2015)
  24. Toxoplasma gondii infection: novel emerging therapeutic targets. Müller J, Hemphill A. Expert Opin Ther Targets 27 293-304 (2023)
  25. Protein kinases on carbon metabolism: potential targets for alternative chemotherapies against toxoplasmosis. Dos Santos DA, Souza HFS, Silber AM, de Souza TACB, Ávila AR. Front Cell Infect Microbiol 13 1175409 (2023)

Articles citing this publication (81)

  1. The systematic functional analysis of Plasmodium protein kinases identifies essential regulators of mosquito transmission. Tewari R, Straschil U, Bateman A, Böhme U, Cherevach I, Gong P, Pain A, Billker O. Cell Host Microbe 8 377-387 (2010)
  2. A Plasmodium calcium-dependent protein kinase controls zygote development and transmission by translationally activating repressed mRNAs. Sebastian S, Brochet M, Collins MO, Schwach F, Jones ML, Goulding D, Rayner JC, Choudhary JS, Billker O. Cell Host Microbe 12 9-19 (2012)
  3. TgCDPK3 regulates calcium-dependent egress of Toxoplasma gondii from host cells. McCoy JM, Whitehead L, van Dooren GG, Tonkin CJ. PLoS Pathog 8 e1003066 (2012)
  4. Discovery of Potent and Selective Inhibitors of Calcium-Dependent Protein Kinase 1 (CDPK1) from C. parvum and T. gondii. Murphy RC, Ojo KK, Larson ET, Castellanos-Gonzalez A, Perera BG, Keyloun KR, Kim JE, Bhandari JG, Muller NR, Verlinde CL, White AC, Merritt EA, Van Voorhis WC, Maly DJ. ACS Med Chem Lett 1 331-335 (2010)
  5. Development of Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) inhibitors with potent anti-toxoplasma activity. Johnson SM, Murphy RC, Geiger JA, DeRocher AE, Zhang Z, Ojo KK, Larson ET, Perera BG, Dale EJ, He P, Reid MC, Fox AM, Mueller NR, Merritt EA, Fan E, Parsons M, Van Voorhis WC, Maly DJ. J Med Chem 55 2416-2426 (2012)
  6. A high-throughput phenotypic screen identifies clofazimine as a potential treatment for cryptosporidiosis. Love MS, Beasley FC, Jumani RS, Wright TM, Chatterjee AK, Huston CD, Schultz PG, McNamara CW. PLoS Negl Trop Dis 11 e0005373 (2017)
  7. Transmission of malaria to mosquitoes blocked by bumped kinase inhibitors. Ojo KK, Pfander C, Mueller NR, Burstroem C, Larson ET, Bryan CM, Fox AM, Reid MC, Johnson SM, Murphy RC, Kennedy M, Mann H, Leibly DJ, Hewitt SN, Verlinde CL, Kappe S, Merritt EA, Maly DJ, Billker O, Van Voorhis WC. J Clin Invest 122 2301-2305 (2012)
  8. A specific inhibitor of PfCDPK4 blocks malaria transmission: chemical-genetic validation. Ojo KK, Eastman RT, Vidadala R, Zhang Z, Rivas KL, Choi R, Lutz JD, Reid MC, Fox AM, Hulverson MA, Kennedy M, Isoherranen N, Kim LM, Comess KM, Kempf DJ, Verlinde CL, Su XZ, Kappe SH, Maly DJ, Fan E, Van Voorhis WC. J Infect Dis 209 275-284 (2014)
  9. Quantitative in vivo analyses reveal calcium-dependent phosphorylation sites and identifies a novel component of the Toxoplasma invasion motor complex. Nebl T, Prieto JH, Kapp E, Smith BJ, Williams MJ, Yates JR, Cowman AF, Tonkin CJ. PLoS Pathog 7 e1002222 (2011)
  10. A novel calcium-dependent protein kinase inhibitor as a lead compound for treating cryptosporidiosis. Castellanos-Gonzalez A, White AC, Ojo KK, Vidadala RS, Zhang Z, Reid MC, Fox AM, Keyloun KR, Rivas K, Irani A, Dann SM, Fan E, Maly DJ, Van Voorhis WC. J Infect Dis 208 1342-1348 (2013)
  11. Development of an Orally Available and Central Nervous System (CNS) Penetrant Toxoplasma gondii Calcium-Dependent Protein Kinase 1 (TgCDPK1) Inhibitor with Minimal Human Ether-a-go-go-Related Gene (hERG) Activity for the Treatment of Toxoplasmosis. Vidadala RS, Rivas KL, Ojo KK, Hulverson MA, Zambriski JA, Bruzual I, Schultz TL, Huang W, Zhang Z, Scheele S, DeRocher AE, Choi R, Barrett LK, Siddaramaiah LK, Hol WG, Fan E, Merritt EA, Parsons M, Freiberg G, Marsh K, Kempf DJ, Carruthers VB, Isoherranen N, Doggett JS, Van Voorhis WC, Maly DJ. J Med Chem 59 6531-6546 (2016)
  12. In Vitro and In Vivo Effects of the Bumped Kinase Inhibitor 1294 in the Related Cyst-Forming Apicomplexans Toxoplasma gondii and Neospora caninum. Winzer P, Müller J, Aguado-Martínez A, Rahman M, Balmer V, Manser V, Ortega-Mora LM, Ojo KK, Fan E, Maly DJ, Van Voorhis WC, Hemphill A. Antimicrob Agents Chemother 59 6361-6374 (2015)
  13. Structural and evolutionary divergence of eukaryotic protein kinases in Apicomplexa. Talevich E, Mirza A, Kannan N. BMC Evol Biol 11 321 (2011)
  14. Bumped kinase inhibitor 1294 treats established Toxoplasma gondii infection. Doggett JS, Ojo KK, Fan E, Maly DJ, Van Voorhis WC. Antimicrob Agents Chemother 58 3547-3549 (2014)
  15. Neospora caninum calcium-dependent protein kinase 1 is an effective drug target for neosporosis therapy. Ojo KK, Reid MC, Kallur Siddaramaiah L, Müller J, Winzer P, Zhang Z, Keyloun KR, Vidadala RS, Merritt EA, Hol WG, Maly DJ, Fan E, Van Voorhis WC, Hemphill A. PLoS One 9 e92929 (2014)
  16. Multiple determinants for selective inhibition of apicomplexan calcium-dependent protein kinase CDPK1. Larson ET, Ojo KK, Murphy RC, Johnson SM, Zhang Z, Kim JE, Leibly DJ, Fox AM, Reid MC, Dale EJ, Perera BG, Kim J, Hewitt SN, Hol WG, Verlinde CL, Fan E, Van Voorhis WC, Maly DJ, Merritt EA. J Med Chem 55 2803-2810 (2012)
  17. Optimizing small molecule inhibitors of calcium-dependent protein kinase 1 to prevent infection by Toxoplasma gondii. Lourido S, Zhang C, Lopez MS, Tang K, Barks J, Wang Q, Wildman SA, Shokat KM, Sibley LD. J Med Chem 56 3068-3077 (2013)
  18. Bumped-Kinase Inhibitors for Cryptosporidiosis Therapy. Hulverson MA, Vinayak S, Choi R, Schaefer DA, Castellanos-Gonzalez A, Vidadala RSR, Brooks CF, Herbert GT, Betzer DP, Whitman GR, Sparks HN, Arnold SLM, Rivas KL, Barrett LK, White AC, Maly DJ, Riggs MW, Striepen B, Van Voorhis WC, Ojo KK. J Infect Dis 215 1275-1284 (2017)
  19. Analysis of Noncanonical Calcium-Dependent Protein Kinases in Toxoplasma gondii by Targeted Gene Deletion Using CRISPR/Cas9. Long S, Wang Q, Sibley LD. Infect Immun 84 1262-1273 (2016)
  20. Development of potent and selective Plasmodium falciparum calcium-dependent protein kinase 4 (PfCDPK4) inhibitors that block the transmission of malaria to mosquitoes. Vidadala RS, Ojo KK, Johnson SM, Zhang Z, Leonard SE, Mitra A, Choi R, Reid MC, Keyloun KR, Fox AM, Kennedy M, Silver-Brace T, Hume JC, Kappe S, Verlinde CL, Fan E, Merritt EA, Van Voorhis WC, Maly DJ. Eur J Med Chem 74 562-573 (2014)
  21. The gatekeeper residue and beyond: homologous calcium-dependent protein kinases as drug development targets for veterinarian Apicomplexa parasites. Keyloun KR, Reid MC, Choi R, Song Y, Fox AMW, Hillesland HK, Zhang Z, Vidadala R, Merritt EA, Lau AOT, Maly DJ, Fan E, Barrett LK, Van Voorhis WC, Ojo KK. Parasitology 141 1499-1509 (2014)
  22. Exploiting the unique ATP-binding pocket of toxoplasma calcium-dependent protein kinase 1 to identify its substrates. Lourido S, Jeschke GR, Turk BE, Sibley LD. ACS Chem Biol 8 1155-1162 (2013)
  23. Benzoylbenzimidazole-based selective inhibitors targeting Cryptosporidium parvum and Toxoplasma gondii calcium-dependent protein kinase-1. Zhang Z, Ojo KK, Johnson SM, Larson ET, He P, Geiger JA, Castellanos-Gonzalez A, White AC, Parsons M, Merritt EA, Maly DJ, Verlinde CL, Van Voorhis WC, Fan E. Bioorg Med Chem Lett 22 5264-5267 (2012)
  24. Allosteric activation of apicomplexan calcium-dependent protein kinases. Ingram JR, Knockenhauer KE, Markus BM, Mandelbaum J, Ramek A, Shan Y, Shaw DE, Schwartz TU, Ploegh HL, Lourido S. Proc Natl Acad Sci U S A 112 E4975-84 (2015)
  25. Substituted imidazopyridazines are potent and selective inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1). Chapman TM, Osborne SA, Bouloc N, Large JM, Wallace C, Birchall K, Ansell KH, Jones HM, Taylor D, Clough B, Green JL, Holder AA. Bioorg Med Chem Lett 23 3064-3069 (2013)
  26. Inhibition of Calcium-Dependent Protein Kinase 1 (CDPK1) In Vitro by Pyrazolopyrimidine Derivatives Does Not Correlate with Sensitivity of Cryptosporidium parvum Growth in Cell Culture. Kuhlenschmidt TB, Rutaganira FU, Long S, Tang K, Shokat KM, Kuhlenschmidt MS, Sibley LD. Antimicrob Agents Chemother 60 570-579 (2016)
  27. Kinobead and Single-Shot LC-MS Profiling Identifies Selective PKD Inhibitors. Golkowski M, Vidadala RS, Lombard CK, Suh HW, Maly DJ, Ong SE. J Proteome Res 16 1216-1227 (2017)
  28. Reduced Activity of Mutant Calcium-Dependent Protein Kinase 1 Is Compensated in Plasmodium falciparum through the Action of Protein Kinase G. Bansal A, Ojo KK, Mu J, Maly DJ, Van Voorhis WC, Miller LH. mBio 7 e02011-16 (2016)
  29. SAR Studies of 5-Aminopyrazole-4-carboxamide Analogues as Potent and Selective Inhibitors of Toxoplasma gondii CDPK1. Huang W, Ojo KK, Zhang Z, Rivas K, Vidadala RS, Scheele S, DeRocher AE, Choi R, Hulverson MA, Barrett LK, Bruzual I, Siddaramaiah LK, Kerchner KM, Kurnick MD, Freiberg GM, Kempf D, Hol WG, Merritt EA, Neckermann G, de Hostos EL, Isoherranen N, Maly DJ, Parsons M, Doggett JS, Van Voorhis WC, Fan E. ACS Med Chem Lett 6 1184-1189 (2015)
  30. Identification of mutations in TgMAPK1 of Toxoplasma gondii conferring resistance to 1NM-PP1. Sugi T, Kobayashi K, Takemae H, Gong H, Ishiwa A, Murakoshi F, Recuenco FC, Iwanaga T, Horimoto T, Akashi H, Kato K. Int J Parasitol Drugs Drug Resist 3 93-101 (2013)
  31. Inhibition of Calcium Dependent Protein Kinase 1 (CDPK1) by Pyrazolopyrimidine Analogs Decreases Establishment and Reoccurrence of Central Nervous System Disease by Toxoplasma gondii. Rutaganira FU, Barks J, Dhason MS, Wang Q, Lopez MS, Long S, Radke JB, Jones NG, Maddirala AR, Janetka JW, El Bakkouri M, Hui R, Shokat KM, Sibley LD. J Med Chem 60 9976-9989 (2017)
  32. Novel N-benzoyl-2-hydroxybenzamide disrupts unique parasite secretory pathway. Fomovska A, Huang Q, El Bissati K, Mui EJ, Witola WH, Cheng G, Zhou Y, Sommerville C, Roberts CW, Bettis S, Prigge ST, Afanador GA, Hickman MR, Lee PJ, Leed SE, Auschwitz JM, Pieroni M, Stec J, Muench SP, Rice DW, Kozikowski AP, McLeod R. Antimicrob Agents Chemother 56 2666-2682 (2012)
  33. Plasmodial Kinase Inhibitors: License to Cure? Cabrera DG, Horatscheck A, Wilson CR, Basarab G, Eyermann CJ, Chibale K. J Med Chem 61 8061-8077 (2018)
  34. A Novel Calcium-Dependent Kinase Inhibitor, Bumped Kinase Inhibitor 1517, Cures Cryptosporidiosis in Immunosuppressed Mice. Castellanos-Gonzalez A, Sparks H, Nava S, Huang W, Zhang Z, Rivas K, Hulverson MA, Barrett LK, Ojo KK, Fan E, Van Voorhis WC, White AC. J Infect Dis 214 1850-1855 (2016)
  35. Two Novel Calcium-Dependent Protein Kinase 1 Inhibitors Interfere with Vertical Transmission in Mice Infected with Neospora caninum Tachyzoites. Müller J, Aguado-Martínez A, Balmer V, Maly DJ, Fan E, Ortega-Mora LM, Ojo KK, Van Voorhis WC, Hemphill A. Antimicrob Agents Chemother 61 e02324-16 (2017)
  36. 1,4-Disubstituted thiosemicarbazide derivatives are potent inhibitors of Toxoplasma gondii proliferation. Dzitko K, Paneth A, Plech T, Pawełczyk J, Stączek P, Stefańska J, Paneth P. Molecules 19 9926-9943 (2014)
  37. Biochemical and antiparasitic properties of inhibitors of the Plasmodium falciparum calcium-dependent protein kinase PfCDPK1. Ansell KH, Jones HM, Whalley D, Hearn A, Taylor DL, Patin EC, Chapman TM, Osborne SA, Wallace C, Birchall K, Large J, Bouloc N, Smiljanic-Hurley E, Clough B, Moon RW, Green JL, Holder AA. Antimicrob Agents Chemother 58 6032-6043 (2014)
  38. A novel CDPK1 inhibitor--a potential treatment for cryptosporidiosis in calves? Lendner M, Böttcher D, Delling C, Ojo KK, Van Voorhis WC, Daugschies A. Parasitol Res 114 335-336 (2015)
  39. Development of 5-Aminopyrazole-4-carboxamide-based Bumped-Kinase Inhibitors for Cryptosporidiosis Therapy. Huang W, Hulverson MA, Choi R, Arnold SLM, Zhang Z, McCloskey MC, Whitman GR, Hackman RC, Rivas KL, Barrett LK, Ojo KK, Van Voorhis WC, Fan E. J Med Chem 62 3135-3146 (2019)
  40. A single mutation in the gatekeeper residue in TgMAPKL-1 restores the inhibitory effect of a bumped kinase inhibitor on the cell cycle. Sugi T, Kawazu S, Horimoto T, Kato K. Int J Parasitol Drugs Drug Resist 5 1-8 (2015)
  41. Bumped kinase inhibitor prohibits egression in Babesia bovis. Pedroni MJ, Vidadala RS, Choi R, Keyloun KR, Reid MC, Murphy RC, Barrett LK, Van Voorhis WC, Maly DJ, Ojo KK, Lau AO. Vet Parasitol 215 22-28 (2016)
  42. Preassembled Single-Stranded RNA-Argonaute Complexes: A Novel Method to Silence Genes in Cryptosporidium. Castellanos-Gonzalez A, Perry N, Nava S, White AC. J Infect Dis 213 1307-1314 (2016)
  43. Safety and efficacy of the bumped kinase inhibitor BKI-1553 in pregnant sheep experimentally infected with Neospora caninum tachyzoites. Sánchez-Sánchez R, Ferre I, Re M, Vázquez P, Ferrer LM, Blanco-Murcia J, Regidor-Cerrillo J, Pizarro Díaz M, González-Huecas M, Tabanera E, García-Lunar P, Benavides J, Castaño P, Hemphill A, Hulverson MA, Whitman GR, Rivas KL, Choi R, Ojo KK, Barrett LK, Van Voorhis WC, Ortega-Mora LM. Int J Parasitol Drugs Drug Resist 8 112-124 (2018)
  44. Trypanosoma brucei glycogen synthase kinase-3, a target for anti-trypanosomal drug development: a public-private partnership to identify novel leads. Oduor RO, Ojo KK, Williams GP, Bertelli F, Mills J, Maes L, Pryde DC, Parkinson T, Van Voorhis WC, Holler TP. PLoS Negl Trop Dis 5 e1017 (2011)
  45. Calcium-dependent Protein Kinases in Malaria Parasite Development and Infection. Ghartey-Kwansah G, Yin Q, Li Z, Gumpper K, Sun Y, Yang R, Wang D, Jones O, Zhou X, Wang L, Bryant J, Ma J, Boampong JN, Xu X. Cell Transplant 29 963689719884888 (2020)
  46. Novel insights into the regulation of malarial calcium-dependent protein kinase 1. Ahmed A, Gaadhe K, Sharma GP, Kumar N, Neculai M, Hui R, Mohanty D, Sharma P. FASEB J 26 3212-3221 (2012)
  47. 1NM-PP1 treatment of mice infected with Toxoplasma gondii. Sugi T, Kato K, Kobayashi K, Kurokawa H, Takemae H, Gong H, Recuenco FC, Iwanaga T, Horimoto T, Akashi H. J Vet Med Sci 73 1377-1379 (2011)
  48. In silico prediction of antimalarial drug target candidates. Ludin P, Woodcroft B, Ralph SA, Mäser P. Int J Parasitol Drugs Drug Resist 2 191-199 (2012)
  49. Expression of the essential Kinase PfCDPK1 from Plasmodium falciparum in Toxoplasma gondii facilitates the discovery of novel antimalarial drugs. Gaji RY, Checkley L, Reese ML, Ferdig MT, Arrizabalaga G. Antimicrob Agents Chemother 58 2598-2607 (2014)
  50. Selective inhibition of Sarcocystis neurona calcium-dependent protein kinase 1 for equine protozoal myeloencephalitis therapy. Ojo KK, Dangoudoubiyam S, Verma SK, Scheele S, DeRocher AE, Yeargan M, Choi R, Smith TR, Rivas KL, Hulverson MA, Barrett LK, Fan E, Maly DJ, Parsons M, Dubey JP, Howe DK, Van Voorhis WC. Int J Parasitol 46 871-880 (2016)
  51. 5-Aminopyrazole-4-carboxamide analogues are selective inhibitors of Plasmodium falciparum microgametocyte exflagellation and potential malaria transmission blocking agents. Huang W, Hulverson MA, Zhang Z, Choi R, Hart KJ, Kennedy M, Vidadala RSR, Maly DJ, Van Voorhis WC, Lindner SE, Fan E, Ojo KK. Bioorg Med Chem Lett 26 5487-5491 (2016)
  52. In Vitro Screening of the Open-Source Medicines for Malaria Venture Malaria Box Reveals Novel Compounds with Profound Activities against Theileria annulata Schizonts. Hostettler I, Müller J, Hemphill A. Antimicrob Agents Chemother 60 3301-3308 (2016)
  53. Neospora caninum: Structure and Fate of Multinucleated Complexes Induced by the Bumped Kinase Inhibitor BKI-1294. Winzer P, Anghel N, Imhof D, Balmer V, Ortega-Mora LM, Ojo KK, Van Voorhis WC, Müller J, Hemphill A. Pathogens 9 E382 (2020)
  54. Identification and Validation of Small-Gatekeeper Kinases as Drug Targets in Giardia lamblia. Hennessey KM, Smith TR, Xu JW, Alas GC, Ojo KK, Merritt EA, Paredez AR. PLoS Negl Trop Dis 10 e0005107 (2016)
  55. In vitro activity, safety and in vivo efficacy of the novel bumped kinase inhibitor BKI-1748 in non-pregnant and pregnant mice experimentally infected with Neospora caninum tachyzoites and Toxoplasma gondii oocysts. Imhof D, Anghel N, Winzer P, Balmer V, Ramseier J, Hänggeli K, Choi R, Hulverson MA, Whitman GR, Arnold SLM, Ojo KK, Van Voorhis WC, Doggett JS, Ortega-Mora LM, Hemphill A. Int J Parasitol Drugs Drug Resist 16 90-101 (2021)
  56. Neospora caninum: Differential Proteome of Multinucleated Complexes Induced by the Bumped Kinase Inhibitor BKI-1294. Winzer P, Müller J, Imhof D, Ritler D, Uldry AC, Braga-Lagache S, Heller M, Ojo KK, Van Voorhis WC, Ortega-Mora LM, Hemphill A. Microorganisms 8 E801 (2020)
  57. Profiling of myristoylation in Toxoplasma gondii reveals an N-myristoylated protein important for host cell penetration. Broncel M, Dominicus C, Vigetti L, Nofal SD, Bartlett EJ, Touquet B, Hunt A, Wallbank BA, Federico S, Matthews S, Young JC, Tate EW, Tardieux I, Treeck M. Elife 9 e57861 (2020)
  58. Treatment with Bumped Kinase Inhibitor 1294 Is Safe and Leads to Significant Protection against Abortion and Vertical Transmission in Sheep Experimentally Infected with Toxoplasma gondii during Pregnancy. Sánchez-Sánchez R, Ferre I, Re M, Ramos JJ, Regidor-Cerrillo J, Pizarro Díaz M, González-Huecas M, Tabanera E, Benavides J, Hemphill A, Hulverson MA, Barrett LK, Choi R, Whitman GR, Ojo KK, Van Voorhis WC, Ortega-Mora LM. Antimicrob Agents Chemother 63 e02527-18 (2019)
  59. TgTKL1 Is a Unique Plant-Like Nuclear Kinase That Plays an Essential Role in Acute Toxoplasmosis. Varberg JM, Coppens I, Arrizabalaga G, Gaji RY. mBio 9 e00301-18 (2018)
  60. An Extracellular Redox Signal Triggers Calcium Release and Impacts the Asexual Development of Toxoplasma gondii. Alves E, Benns HJ, Magnus L, Dominicus C, Dobai T, Blight J, Wincott CJ, Child MA. Front Cell Infect Microbiol 11 728425 (2021)
  61. Bumped kinase inhibitor 1369 is effective against Cystoisospora suis in vivo and in vitro. Shrestha A, Ojo KK, Koston F, Ruttkowski B, Vidadala RSR, Dorr CS, Navaluna ED, Whitman GR, Barrett KF, Barrett LK, Hulverson MA, Choi R, Michaels SA, Maly DJ, Hemphill A, Van Voorhis WC, Joachim A. Int J Parasitol Drugs Drug Resist 10 9-19 (2019)
  62. Molecular Characterization and Functional Analysis of a Novel Calcium-Dependent Protein Kinase 4 from Eimeria tenella. Wang Z, Huang B, Dong H, Zhao Q, Zhu S, Xia W, Xu S, Xie Y, Cui X, Tang M, Men Q, Yang Z, Li C, Zhu X, Han H. PLoS One 11 e0168132 (2016)
  63. The Impact of BKI-1294 Therapy in Mice Infected With the Apicomplexan Parasite Neospora caninum and Re-infected During Pregnancy. Winzer P, Imhof D, Anghel N, Ritler D, Müller J, Boubaker G, Aguado-Martinez A, Ortega-Mora LM, Ojo KK, VanVoorhis WC, Hemphill A. Front Vet Sci 7 587570 (2020)
  64. 7 H-Pyrrolo[2,3- d]pyrimidin-4-amine-Based Inhibitors of Calcium-Dependent Protein Kinase 1 Have Distinct Inhibitory and Oral Pharmacokinetic Characteristics Compared with 1 H-Pyrazolo[3,4- d]pyrimidin-4-amine-Based Inhibitors. Vidadala RSR, Golkowski M, Hulverson MA, Choi R, McCloskey MC, Whitman GR, Huang W, Arnold SLM, Barrett LK, Fan E, Merritt EA, Van Voorhis WC, Ojo KK, Maly DJ. ACS Infect Dis 4 516-522 (2018)
  65. Comparative assessment of the effects of bumped kinase inhibitors on early zebrafish embryo development and pregnancy in mice. Anghel N, Winzer PA, Imhof D, Müller J, Langa X, Rieder J, Barrett LK, Vidadala RSR, Huang W, Choi R, Hulverson MA, Whitman GR, Arnold SL, Van Voorhis WC, Ojo KK, Maly DJ, Fan E, Hemphill A. Int J Antimicrob Agents 56 106099 (2020)
  66. Toxoplasma Calcium-Dependent Protein Kinase 1 Inhibitors: Probing Activity and Resistance Using Cellular Thermal Shift Assays. Scheele S, Geiger JA, DeRocher AE, Choi R, Smith TR, Hulverson MA, Vidadala RSR, Barrett LK, Maly DJ, Merritt EA, Ojo KK, Van Voorhis WC, Parsons M. Antimicrob Agents Chemother 62 e00051-18 (2018)
  67. Characterization of a Toxoplasma gondii calcium calmodulin-dependent protein kinase homolog. Kato K, Sugi T, Takemae H, Takano R, Gong H, Ishiwa A, Horimoto T, Akashi H. Parasit Vectors 9 405 (2016)
  68. Common Molecular Targets of a Quinolone Based Bumped Kinase Inhibitor in Neospora caninum and Danio rerio. Müller J, Anghel N, Imhof D, Hänggeli K, Uldry AC, Braga-Lagache S, Heller M, Ojo KK, Ortega-Mora LM, Van Voorhis WC, Hemphill A. Int J Mol Sci 23 2381 (2022)
  69. Discovery of a potent protein kinase D inhibitor: insights in the binding mode of pyrazolo[3,4-d]pyrimidine analogues. Verschueren K, Cobbaut M, Demaerel J, Saadah L, Voet ARD, Van Lint J, De Borggraeve WM. Medchemcomm 8 640-646 (2017)
  70. In vitro growth inhibition of Theileria equi by bumped kinase inhibitors. Gimenez F, Hines SA, Evanoff R, Ojo KK, Van Voorhis WC, Maly DJ, Vidadala RSR, Mealey RH. Vet Parasitol 251 90-94 (2018)
  71. Repurposing the Kinase Inhibitor Mavelertinib for Giardiasis Therapy. Michaels SA, Hulverson MA, Whitman GR, Tran LT, Choi R, Fan E, McNamara CW, Love MS, Ojo KK. Antimicrob Agents Chemother 66 e0001722 (2022)
  72. A parasite calcium switch and Achilles' heel revealed. Doerig C, Billker O. Nat Struct Mol Biol 17 541-543 (2010)
  73. A short-term treatment with BKI-1294 does not protect foetuses from sheep experimentally infected with Neospora caninum tachyzoites during pregnancy. Sánchez-Sánchez R, Ferre I, Re M, Pérez-Arroyo B, Cleofé-Resta D, García VH, Díaz MP, Ferrer LM, Ruiz H, Vallejo-García R, Benavides J, Hulverson MA, Choi R, Whitman GR, Hemphill A, Van Voorhis WC, Ortega-Mora LM. Int J Parasitol Drugs Drug Resist 17 176-185 (2021)
  74. Optimizing Pyrazolopyrimidine Inhibitors of Calcium Dependent Protein Kinase 1 for Treatment of Acute and Chronic Toxoplasmosis. Janetka JW, Hopper AT, Yang Z, Barks J, Dhason MS, Wang Q, Sibley LD. J Med Chem 63 6144-6163 (2020)
  75. Pyrrolopyrimidine Bumped Kinase Inhibitors for the Treatment of Cryptosporidiosis. Hulverson MA, Choi R, Vidadala RSR, Whitman GR, Vidadala VN, Ojo KK, Barrett LK, Lynch JJ, Marsh K, Kempf DJ, Maly DJ, Van Voorhis WC. ACS Infect Dis 7 1200-1207 (2021)
  76. Analysis of CDPK1 targets identifies a trafficking adaptor complex that regulates microneme exocytosis in Toxoplasma. Chan AW, Broncel M, Yifrach E, Haseley NR, Chakladar S, Andree E, Herneisen AL, Shortt E, Treeck M, Lourido S. Elife 12 RP85654 (2023)
  77. Calcium binding properties of calcium dependent protein kinase 1 (CaCDPK1) from Cicer arietinum. Dixit AK, Jayabaskaran C. J Plant Physiol 179 106-112 (2015)
  78. Genome-Wide Identification and Evolutionary Analysis of Sarcocystis neurona Protein Kinases. Murungi EK, Kariithi HM. Pathogens 6 E12 (2017)
  79. Serial Dissection of Parasite Gene Families. Bzik DJ. Infect Immun 84 1252-1254 (2016)
  80. Comparison of Toxicities among Different Bumped Kinase Inhibitor Analogs for Treatment of Cryptosporidiosis. Hulverson MA, Choi R, Schaefer DA, Betzer DP, McCloskey MC, Whitman GR, Huang W, Lee S, Pranata A, McLeod MD, Marsh KC, Kempf DJ, LeRoy BE, Zafiratos MT, Bielinski AL, Hackman RC, Ojo KK, Arnold SLM, Barrett LK, Tzipori S, Riggs MW, Fan E, Van Voorhis WC. Antimicrob Agents Chemother 67 e0142522 (2023)
  81. Computational screening of FDA-approved drugs to identify potential TgDHFR, TgPRS, and TgCDPK1 proteins inhibitors against Toxoplasma gondii. Gharibi Z, Shahbazi B, Gouklani H, Nassira H, Rezaei Z, Ahmadi K. Sci Rep 13 5396 (2023)


Related citations provided by authors (1)

  1. Discovery of Potent and Selective Inhibitors of Calcium-Dependent Protein Kinase 1 (CDPK1) from C. parvum and T. gondii.. Murphy RC, Ojo KK, Larson ET, Castellanos-Gonzalez A, Perera BG, Keyloun KR, Kim JE, Bhandari JG, Muller NR, Verlinde CL, White AC, Merritt EA, Van Voorhis WC, Maly DJ ACS Med Chem Lett 1 331-335 (2010)

Quick links