Pharmacology - Phillips Lab

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2020

Lead optimization of a pyrrole-based dihydroorotate dehydrogenase inhibitor series for the treatment of malaria

Kokkonda, S., Deng, X., White, K. L., El Mazouni, F., White, J., Shackleford, D. M., Katneni, K., Chiu, F. C. K., Barker, H., Mclaren, J., Crighton, E., Chen, G., Angulo-Barturen, I., Jimenez-Diaz, M. B., Ferrer, S., Huertas-Valentin, L., Martinez-Martinez, M. S., Lafuente-Monasterio, M. J., Chittimalla, R., Shahi, S. P. & 9 others, Wittlin, S., Waterson, D., Burrows, J. N., Matthews, D., Tomchick, D., Rathod, P. K., Palmer, M. J., Charman, S. A. & Phillips, M. A., May 14 2020, In : Journal of Medicinal Chemistry. 63, 9, p. 4929-4956 28 p.

Research output: Contribution to journalArticle

2019

Activation mechanism of the insulin receptor revealed by cryo-EM structure of the fully liganded receptor-ligand complex

Uchikawa, E., Choi, E., Shang, G., Yu, H. & Xiao-Chen, B., Aug 2019, In : eLife. 8, e48630.

Research output: Contribution to journalArticle

Open Access
8 Scopus citations

Mitotic regulators and the SHP2-MAPK pathway promote IR endocytosis and feedback regulation of insulin signaling

Choi, E., Kikuchi, S., Gao, H., Brodzik, K., Nassour, I., Yopp, A., Singal, A. G., Zhu, H. & Yu, H., Dec 1 2019, In : Nature communications. 10, 1, 1473.

Research output: Contribution to journalArticle

Open Access
7 Scopus citations

Mps1 regulates spindle morphology through MCRS1 to promote chromosome alignment

Yang, H., Zhang, F., Huang, C. J., Liao, J., Han, Y., Hao, P., Chu, Y., Lu, X., Li, W., Yu, H. & Kang, J., Jan 1 2019, In : Molecular Biology of the Cell. 30, 9, p. 1060-1068 9 p.

Research output: Contribution to journalArticle

PUMILIO hyperactivity drives premature aging of norad-deficient mice

Kopp, F., Elguindy, M. M., Yalvac, M. E., Zhang, H., Chen, B., Gillett, F. A., Lee, S., Sivakumar, S., Yu, H., Xie, Y., Mishra, P., Sahenk, Z. & Mendell, J. T., Feb 2019, In : eLife. 8, e42650.

Research output: Contribution to journalArticle

Open Access
10 Scopus citations

Structural basis of the activation of type 1 insulin-like growth factor receptor

Li, J., Choi, E., Yu, H. & Bai, X. C., Dec 1 2019, In : Nature communications. 10, 1, 4567.

Research output: Contribution to journalArticle

Open Access
5 Scopus citations

Structural basis of tubulin detyrosination by vasohibins

Li, F., Hu, Y., Qi, S., Luo, X. & Yu, H., Jul 1 2019, In : Nature Structural and Molecular Biology. 26, 7, p. 583-591 9 p.

Research output: Contribution to journalArticle

4 Scopus citations
2018
1 Scopus citations

Antimalarial activity of single-dose DSM265, a novel plasmodium dihydroorotate dehydrogenase inhibitor, in patients with uncomplicated Plasmodium falciparum or Plasmodium vivax malaria infection: a proof-of-concept, open-label, phase 2a study

Llanos-Cuentas, A., Casapia, M., Chuquiyauri, R., Hinojosa, J. C., Kerr, N., Rosario, M., Toovey, S., Arch, R. H., Phillips, M. A., Rozenberg, F. D., Bath, J., Ng, C. L., Cowell, A. N., Winzeler, E. A., Fidock, D. A., Baker, M., Möhrle, J. J., Hooft van Huijsduijnen, R., Gobeau, N., Araeipour, N. & 3 others, Andenmatten, N., Rückle, T. & Duparc, S., Jan 1 2018, (Accepted/In press) In : The Lancet Infectious Diseases.

Research output: Contribution to journalArticle

22 Scopus citations

Assessing drug efficacy against Plasmodium falciparum liver stages in vivo

Flannery, E. L., Foquet, L., Chuenchob, V., Fishbaugher, M., Billman, Z., Navarro, M. J., Betz, W., Olsen, T. M., Lee, J., Camargo, N., Nguyen, T., Schafer, C., Sack, B. K., Wilson, E. M., Saunders, J., Bial, J., Campo, B., Charman, S. A., Murphy, S. C., Phillips, M. A. & 2 others, Kappe, S. H. & Mikolajczak, S. A., Jan 11 2018, In : JCI insight. 3, 1

Research output: Contribution to journalArticle

Open Access
6 Scopus citations

Identification and Mechanistic Understanding of Dihydroorotate Dehydrogenase Point Mutations in Plasmodium falciparum that Confer in Vitro Resistance to the Clinical Candidate DSM265

White, J., Dhingra, S. K., Deng, X., El Mazouni, F., Lee, M. C. S., Afanador, G. A., Lawong, A., Tomchick, D. R., Ng, C. L., Bath, J., Rathod, P. K., Fidock, D. A. & Phillips, M. A., Jan 1 2018, (Accepted/In press) In : ACS Infectious Diseases.

Research output: Contribution to journalArticle

5 Scopus citations

Interaction of the Warsaw breakage syndrome DNA helicase DDX11 with the replication fork-protection factor Timeless promotes sister chromatid cohesion

Cortone, G., Zheng, G., Pensieri, P., Chiappetta, V., Tatè, R., Malacaria, E., Pichierri, P., Yu, H. & Pisani, F. M., Oct 1 2018, In : PLoS Genetics. 14, 10, p. e1007622

Research output: Contribution to journalArticle

9 Scopus citations

Isoxazolopyrimidine-Based Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase with Antimalarial Activity

Kokkonda, S., El Mazouni, F., White, K. L., White, J., Shackleford, D. M., Lafuente-Monasterio, M. J., Rowland, P., Manjalanagara, K., Joseph, J. T., Garcia-Pérez, A., Fernandez, J., Gamo, F. J., Waterson, D., Burrows, J. N., Palmer, M. J., Charman, S. A., Rathod, P. K. & Phillips, M. A., Aug 31 2018, In : ACS Omega. 3, 8, p. 9227-9240 14 p.

Research output: Contribution to journalArticle

6 Scopus citations

MCM2–7-dependent cohesin loading during s phase promotes sister-chromatid cohesion

Zheng, G., Kanchwala, M., Xing, C. & Yu, H., Apr 3 2018, In : eLife. 7, e33920.

Research output: Contribution to journalArticle

18 Scopus citations

Partner switching for Ran during the mitosis dance

Yang, Y. & Yu, H., Feb 1 2018, In : Journal of molecular cell biology. 10, 1, p. 89-90 2 p.

Research output: Contribution to journalArticle

Open Access
4 Scopus citations

Scc2 Is a Potent Activator of Cohesin's ATPase that Promotes Loading by Binding Scc1 without Pds5

Petela, N. J., Gligoris, T. G., Metson, J., Lee, B. G., Voulgaris, M., Hu, B., Kikuchi, S., Chapard, C., Chen, W., Rajendra, E., Srinivisan, M., Yu, H., Löwe, J. & Nasmyth, K. A., Jun 21 2018, In : Molecular cell. 70, 6, p. 1134-1148.e7

Research output: Contribution to journalArticle

26 Scopus citations

Species-Selective Pyrimidineamine Inhibitors of Trypanosoma brucei S-Adenosylmethionine Decarboxylase

Volkov, O. A., Brockway, A. J., Wring, S. A., Peel, M., Chen, Z., Phillips, M. A. & De Brabander, J. K., Feb 8 2018, In : Journal of Medicinal Chemistry. 61, 3, p. 1182-1203 22 p.

Research output: Contribution to journalArticle

5 Scopus citations

Sumoylation promotes optimal apc/c activation and timely anaphase

Lee, C. C., Li, B., Yu, H. & Matunis, M. J., Mar 8 2018, In : eLife. 7, e29539.

Research output: Contribution to journalArticle

9 Scopus citations

The BUB3-BUB1 Complex Promotes Telomere DNA Replication

Li, F., Kim, H., Ji, Z., Zhang, T., Chen, B., Ge, Y., Hu, Y., Feng, X., Han, X., Xu, H., Zhang, Y., Yu, H., Liu, D., Ma, W. & Songyang, Z., Jan 1 2018, (Accepted/In press) In : Molecular Cell.

Research output: Contribution to journalArticle

12 Scopus citations

The chromatin remodeler RSF1 controls centromeric histone modifications to coordinate chromosome segregation

Lee, H. S., Lin, Z., Chae, S., Yoo, Y. S., Kim, B. G., Lee, Y., Johnson, J. L., Kim, Y. S., Cantley, L. C., Lee, C. W., Yu, H. & Cho, H., Dec 1 2018, In : Nature communications. 9, 1, 3848.

Research output: Contribution to journalArticle

5 Scopus citations

Trypanosomatid Deoxyhypusine Synthase Activity Is Dependent on Shared Active-Site Complementation between Pseudoenzyme Paralogs

Afanador, G. A., Tomchick, D. R. & Phillips, M. A., Nov 6 2018, In : Structure. 26, 11, p. 1499-1512.e5

Research output: Contribution to journalArticle

4 Scopus citations
2017

A sequential multi-target Mps1 phosphorylation cascade promotes spindle checkpoint signaling

Ji, Z., Gao, H., Jia, L., Li, B. & Yu, H., Jan 10 2017, In : eLife. 6, e22513.

Research output: Contribution to journalArticle

51 Scopus citations

Familial stag2 germline mutation defines a new human cohesinopathy

Soardi, F. C., Machado-Silva, A., Linhares, N. D., Zheng, G., Qu, Q., Pena, H. B., Martins, T. M. M., Vieira, H. G. S., Pereira, N. B., Melo-Minardi, R. C., Gomes, C. C., Gomez, R. S., Gomes, D. A., Pires, D. E. V., Ascher, D. B., Yu, H. & Pena, S. D. J., Dec 1 2017, In : npj Genomic Medicine. 2, 1, 7.

Research output: Contribution to journalArticle

20 Scopus citations

Identification of Trypanosoma brucei AdoMetDC Inhibitors Using a High-Throughput Mass Spectrometry-Based Assay

Volkov, O. A., Cosner, C. C., Brockway, A. J., Kramer, M., Booker, M., Zhong, S., Ketcherside, A., Wei, S., Longgood, J., McCoy, M., Richardson, T. E., Wring, S. A., Peel, M., Klinger, J. D., Posner, B. A., De Brabander, J. K. & Phillips, M. A., Jul 14 2017, In : ACS Infectious Diseases. 3, 7, p. 512-526 15 p.

Research output: Contribution to journalArticle

8 Scopus citations

Malaria

Phillips, M. A., Burrows, J. N., Manyando, C., Van Huijsduijnen, R. H., Van Voorhis, W. C. & Wells, T. N. C., Aug 3 2017, In : Nature Reviews Disease Primers. 3, 17050.

Research output: Contribution to journalArticle

120 Scopus citations

Mechanistic insight into TRIP13-catalyzed Mad2 structural transition and spindle checkpoint silencing

Brulotte, M. L., Jeong, B. C., Li, F., Li, B., Yu, E. B., Wu, Q., Brautigam, C. A., Yu, H. & Luo, X., Dec 1 2017, In : Nature communications. 8, 1, 1956.

Research output: Contribution to journalArticle

10 Scopus citations

Mitotic transcription and waves of gene reactivation during mitotic exit

Palozola, K. C., Donahue, G., Liu, H., Grant, G. R., Becker, J. S., Cote, A., Yu, H., Raj, A. & Zaret, K. S., Oct 6 2017, In : Science. 358, 6359, p. 119-122 4 p.

Research output: Contribution to journalArticle

49 Scopus citations

Releasing the cohesin ring: A rigid scaffold model for opening the DNA exit gate by Pds5 and Wapl

Ouyang, Z. & Yu, H., 2017, (Accepted/In press) In : BioEssays.

Research output: Contribution to journalArticle

15 Scopus citations

Safety, tolerability, pharmacokinetics, and activity of the novel long-acting antimalarial DSM265: a two-part first-in-human phase 1a/1b randomised study

McCarthy, J. S., Lotharius, J., Rückle, T., Chalon, S., Phillips, M. A., Elliott, S., Sekuloski, S., Griffin, P., Ng, C. L., Fidock, D. A., Marquart, L., Williams, N. S., Gobeau, N., Bebrevska, L., Rosario, M., Marsh, K. & Möhrle, J. J., Jun 1 2017, In : The Lancet Infectious Diseases. 17, 6, p. 626-635 10 p.

Research output: Contribution to journalArticle

45 Scopus citations

Ska3 Phosphorylated by Cdk1 Binds Ndc80 and Recruits Ska to Kinetochores to Promote Mitotic Progression

Zhang, Q., Sivakumar, S., Chen, Y., Gao, H., Yang, L., Yuan, Z., Yu, H. & Liu, H., May 22 2017, In : Current Biology. 27, 10, p. 1477-1484.e4

Research output: Contribution to journalArticle

23 Scopus citations

Synthesis and evaluation of analogs of 5'-(((Z)-4-amino-2-butenyl)methylamino)-5'-deoxyadenosine (MDL 73811, or AbeAdo) - An inhibitor of S-adenosylmethionine decarboxylase with antitrypanosomal activity

Brockway, A. J., Volkov, O. A., Cosner, C. C., MacMillan, K. S., Wring, S. A., Richardson, T. E., Peel, M., Phillips, M. A. & De Brabander, J. K., 2017, (Accepted/In press) In : Bioorganic and Medicinal Chemistry.

Research output: Contribution to journalArticle

3 Scopus citations
2016

A Triazolopyrimidine-Based Dihydroorotate Dehydrogenase Inhibitor with Improved Drug-like Properties for Treatment and Prevention of Malaria

Phillips, M. A., White, K. L., Kokkonda, S., Deng, X., White, J., El Mazouni, F., Marsh, K., Tomchick, D. R., Manjalanagara, K., Rudra, K. R., Wirjanata, G., Noviyanti, R., Price, R. N., Marfurt, J., Shackleford, D. M., Chiu, F. C. K., Campbell, M., Jimenez-Diaz, M. B., Bazaga, S. F., Angulo-Barturen, I. & 16 others, Martinez, M. S., Lafuente-Monasterio, M., Kaminsky, W., Silue, K., Zeeman, A. M., Kocken, C., Leroy, D., Blasco, B., Rossignol, E., Rueckle, T., Matthews, D., Burrows, J. N., Waterson, D., Palmer, M. J., Rathod, P. K. & Charman, S. A., Dec 9 2016, In : ACS Infectious Diseases. 2, 12, p. 945-957 13 p.

Research output: Contribution to journalArticle

38 Scopus citations

Control of APC/C-dependent ubiquitin chain elongation by reversible phosphorylation

Craney, A., Kelly, A., Jia, L., Fedrigo, I., Yu, H. & Rape, M., Feb 9 2016, In : Proceedings of the National Academy of Sciences of the United States of America. 113, 6, p. 1540-1545 6 p.

Research output: Contribution to journalArticle

26 Scopus citations
31 Scopus citations

Evaluation of antigens for development of a serological test for human african trypanosomiasis

Biéler, S., Waltenberger, H., Barrett, M. P., McCulloch, R., Mottram, J. C., Carrington, M., Schwaeble, W., McKerrowa, J., Phillips, M. A., Michels, P. A., Büscher, P., Sanchez, J. C., Bishop, R., Robinson, D. R., Bangsb, J., Ferguson, M., Nerima, B., Albertini, A., Michel, G., Radwandskac, M. & 1 others, Ndung'U, J. M., Dec 2016, In : PloS one. 11, 12, e0168074.

Research output: Contribution to journalArticle

3 Scopus citations

Identification of New Human Malaria Parasite Plasmodium falciparum Dihydroorotate Dehydrogenase Inhibitors by Pharmacophore and Structure-Based Virtual Screening

Pavadai, E., El Mazouni, F., Wittlin, S., De Kock, C., Phillips, M. A. & Chibale, K., Mar 28 2016, In : Journal of Chemical Information and Modeling. 56, 3, p. 548-562 15 p.

Research output: Contribution to journalArticle

38 Scopus citations

Improved Synthesis of MDL 73811 - A Potent AdoMetDC Inhibitor and Anti-Trypanosomal Compound

Brockway, A. J., Cosner, C. C., Volkov, O. A., Phillips, M. A. & De Brabander, J. K., Jul 1 2016, In : Synthesis (Germany). 48, 13, p. 2065-2068 4 p., ss-2016-m0105-op.

Research output: Contribution to journalArticle

2 Scopus citations

Magic Acts with the Cohesin Ring

Yu, H., Feb 18 2016, In : Molecular Cell. 61, 4, p. 489-491 3 p.

Research output: Contribution to journalArticle

5 Scopus citations

Mitotic Checkpoint Regulators Control Insulin Signaling and Metabolic Homeostasis

Choi, E., Zhang, X., Xing, C. & Yu, H., Jul 28 2016, In : Cell. 166, 3, p. 567-581 15 p.

Research output: Contribution to journalArticle

28 Scopus citations

Noncoding RNA NORAD Regulates Genomic Stability by Sequestering PUMILIO Proteins

Lee, S., Kopp, F., Chang, T. C., Sataluri, A., Chen, B., Sivakumar, S., Yu, H., Xie, Y. & Mendell, J. T., Jan 14 2016, In : Cell. 164, 1-2, p. 69-80 12 p.

Research output: Contribution to journalArticle

249 Scopus citations

Opposing functions of the N-terminal acetyltransferases Naa50 and NatA in sister-chromatid cohesion

Rong, Z., Ouyang, Z., Magin, R. S., Marmorstein, R. & Yu, H., Sep 2 2016, In : Journal of Biological Chemistry. 291, 36, p. 19079-19091 13 p.

Research output: Contribution to journalArticle

5 Scopus citations

Pyrimidine Salvage Enzymes Are Essential for De Novo Biosynthesis of Deoxypyrimidine Nucleotides in Trypanosoma brucei

Leija, C., Rijo-Ferreira, F., Kinch, L. N., Grishin, N. V., Nischan, N., Kohler, J. J., Hu, Z. & Phillips, M. A., Nov 1 2016, In : PLoS Pathogens. 12, 11, e1006010.

Research output: Contribution to journalArticle

11 Scopus citations

Relief of autoinhibition by conformational switch explains enzyme activation by a catalytically dead paralog

Volkov, O. A., Kinch, L., Ariagno, C., Deng, X., Zhong, S., Grishin, N., Tomchick, D. R., Chen, Z. & Phillips, M. A., Dec 15 2016, In : eLife. 5, DECEMBER2016, e20198.

Research output: Contribution to journalArticle

13 Scopus citations

Structural basis of cohesin cleavage by separase

Lin, Z., Luo, X. & Yu, H., Apr 7 2016, In : Nature. 532, 7597, p. 131-134 4 p.

Research output: Contribution to journalArticle

30 Scopus citations

Tetrahydro-2-naphthyl and 2-Indanyl Triazolopyrimidines Targeting Plasmodium falciparum Dihydroorotate Dehydrogenase Display Potent and Selective Antimalarial Activity

Kokkonda, S., Deng, X., White, K. L., Coteron, J. M., Marco, M., De Las Heras, L., White, J., El Mazouni, F., Tomchick, D. R., Manjalanagara, K., Rudra, K. R., Chen, G., Morizzi, J., Ryan, E., Kaminsky, W., Leroy, D., Martínez-Martínez, M. S., Jimenez-Diaz, M. B., Bazaga, S. F., Angulo-Barturen, I. & 6 others, Waterson, D., Burrows, J. N., Matthews, D., Charman, S. A., Phillips, M. A. & Rathod, P. K., Jun 9 2016, In : Journal of Medicinal Chemistry. 59, 11, p. 5416-5431 16 p.

Research output: Contribution to journalArticle

31 Scopus citations

The Bub1-Plk1 kinase complex promotes spindle checkpoint signalling through Cdc20 phosphorylation

Jia, L., Li, B. & Yu, H., Feb 25 2016, In : Nature Communications. 7, 10818.

Research output: Contribution to journalArticle

49 Scopus citations

The human SKA complex drives the metaphase-anaphase cell cycle transition by recruiting protein phosphatase 1 to kinetochores

Sivakumar, S., Janczyk, P., Qu, Q., Brautigam, C. A., Stukenberg, P. T., Yu, H. & Gorbsky, G. J., Mar 16 2016, In : eLife. 5, MARCH2016, e12902.

Research output: Contribution to journalArticle

36 Scopus citations
2015

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

Phillips, M. A., Lotharius, J., Marsh, K., White, J., Dayan, A., White, K. L., Njoroge, J. W., El Mazouni, F., Lao, Y., Kokkonda, S., Tomchick, D. R., Deng, X., Laird, T., Bhatia, S. N., March, S., Ng, C. L., Fidock, D. A., Wittlin, S., Lafuente-Monasterio, M., Benito, F. J. G. & 33 others, Alonso, L. M. S., Martinez, M. S., Jimenez-Diaz, M. B., Bazaga, S. F., Angulo-Barturen, I., Haselden, J. N., Louttit, J., Cui, Y., Sridhar, A., Zeeman, A. M., Kocken, C., Sauerwein, R., Dechering, K., Avery, V. M., Duffy, S., Delves, M., Sinden, R., Ruecker, A., Wickham, K. S., Rochford, R., Gahagen, J., Iyer, L., Riccio, E., Mirsalis, J., Bathhurst, I., Rueckle, T., Ding, X., Campo, B., Leroy, D., Rogers, M. J., Rathod, P. K., Burrows, J. N. & Charman, S. A., Jul 15 2015, In : Science translational medicine. 7, 296, aaa6645.

Research output: Contribution to journalArticle

125 Scopus citations

A teach-discover-treat application of ZincPharmer: An online interactive pharmacophore modeling and virtual screening tool

Koes, D. R., Pabon, N. A., Deng, X., Phillips, M. A. & Camacho, C. J., Aug 10 2015, In : PLoS One. 10, 8, e0134697.

Research output: Contribution to journalArticle

7 Scopus citations

Atovaquone tolerance in plasmodium falciparum parasites selected for high-level resistance to a dihydroorotate dehydrogenase inhibitor

Guler, J. L., White, J., Phillips, M. A. & Rathoda, P. K., Jan 1 2015, In : Antimicrobial agents and chemotherapy. 59, 1, p. 686-689 4 p.

Research output: Contribution to journalArticle

7 Scopus citations