Identification of a Small Molecule Inhibitor of RAD52 by Structure-Based Selection

PLoS ONE

Volumn 11, Issue 1, 2016, Pages

  Sullivan, Katherine ^a   Cramer Morales, Kimberly ^a   McElroy, Daniel L ^b   Ostrov, David A ^b   Haas, Kimberly ^c   Childers, Wayne ^c   Hromas, Robert ^b   Skorski, Tomasz ^a  

^a TEMPLE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^c TEMPLE UNIVERSITY SCHOOL OF PHARMACY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 (4 BENZYL 2,5 DIOXO 1 IMIDAZOLIDINYL) 3 PHENYLPROPANOIC ACID; 5 AMINOIMIDAZOLE 4 CARBOXAMIDE RIBONUCLEOTIDE 5' PHOSPHATE; 6 (1 AZIRIDINYL) 7 METHYL 5,8 DIOXO 2,3,5,8 TETRAHYDRO 1H PYRROLO[1,2 A]BENZIMIDAZOL 3 YL PROPIONATE; 6 CHLORO 3 (DICHLOROMETHYL) 3,4 DIHYDRO 2H 1,2,4 BENZOTHIADIAZINE 7 SULFONAMIDE1,1 DIOXIDE; 6 [[(1AMINOCYCLOHEXYL)CARBONYL]AMINO] 3,3 DIMETHYL 7 OXO 4 THIA 1 AZABICYCLO[3.2.0]HEPTANE 2 CARBOXYLIC ACID; 9 [5 (HYDROXYMETHYL)TETRAHYDRO 2 FURANYL] 9H PURIN 6 OL; ADENOSINE PHOSPHATE; BRCA1 PROTEIN; BRCA2 PROTEIN; CYTARABINE; N (DICHLOROACETYL)ASPARTIC ACID; PROTEIN INHIBITOR; RAD52 PROTEIN; SINGLE STRANDED DNA; UNCLASSIFIED DRUG; [(1,3,9 TRIMETHYL 2,6 DIOXO 2,3,6,9 TETRAHYDRO 1H PURIN 8 YL)THIO]ACETIC ACID; BRCA1 PROTEIN, HUMAN; MOLECULAR LIBRARY; RAD52 PROTEIN, HUMAN;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DNA BINDING; DRUG APPROVAL; DRUG DNA INTERACTION; DRUG EFFICACY; DRUG INHIBITION; DRUG MECHANISM; DRUG SAFETY; DRUG STRUCTURE; HUMAN; HUMAN CELL; IN VITRO STUDY; MOLECULAR DOCKING; PROTEIN DOMAIN; PROTEIN EXPRESSION; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; BREAST NEOPLASMS; CHEMISTRY; DEFICIENCY; FEMALE; GENETICS; GERMLINE MUTATION; METABOLISM; MOLECULAR LIBRARY; MOLECULAR MODEL; PATHOLOGY; PHARMACOLOGY; PROTEIN CONFORMATION; TUMOR CELL CULTURE;

BRCA1 PROTEIN; BREAST NEOPLASMS; DNA, SINGLE-STRANDED; FEMALE; GERM-LINE MUTATION; HUMANS; MODELS, MOLECULAR; MOLECULAR DOCKING SIMULATION; PROTEIN CONFORMATION; RAD52 DNA REPAIR AND RECOMBINATION PROTEIN; SMALL MOLECULE LIBRARIES; TUMOR CELLS, CULTURED;

EID: 84958231283     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0147230     Document Type: Article

References (29)

1. Helleday T, Petermann E, Lundin C, Hodgson B, Sharma RA. DNA repair pathways as targets for cancer therapy. Nat Rev Cancer. 2008; 8(3):193-204. PMID: 18256616 doi: 10.1038/nrc2342
2. Karanam K, Kafri R, Loewer A, Lahav G. Quantitative live cell imaging reveals a gradual shift between DNA repair mechanisms and a maximal use of HR in mid S phase. Mol Cell. 2012; 47(2):320-9. doi: S1097-2765(12)00554-0 PMID: 22841003 doi: 10.1016/j.molcel.2012.05.052
3. Budke B, Logan HL, Kalin JH, Zelivianskaia AS, Cameron McGuire W, Miller LL, et al. RI-1: a chemical inhibitor of RAD51 that disrupts homologous recombination in human cells. Nucleic Acids Res. 2012. doi: gks353 PMID: 22573178
4. Sonoda E, Sasaki MS, Buerstedde JM, Bezzubova O, Shinohara A, Ogawa H, et al. Rad51-deficient vertebrate cells accumulate chromosomal breaks prior to cell death. EMBO J. 1998; 17:598-608. PMID: 9430650
5. Elliott B, Jasin M. Double-strand breaks and translocations in cancer. Cell Mol Life Sci. 2002; 59 (2):373-85 PMID: 11915950
6. Yap TA, Sandhu SK, Carden CP, de Bono JS. Poly(ADP-ribose) polymerase (PARP) inhibitors: Exploiting a synthetic lethal strategy in the clinic. CA Cancer J Clin. 2011; 61(1):31-49. PMID: 21205831 doi: 10.3322/caac.20095
7. Wahlberg E, Karlberg T, Kouznetsova E, Markova N, Macchiarulo A, Thorsell AG, et al. Family-wide chemical profiling and structural analysis of PARP and tankyrase inhibitors. Nat Biotechnol. 2012; 30 (3):283-8. PMID: 22343925 doi: 10.1038/nbt.2121
8. Tallis M, Morra R, Barkauskaite E, Ahel I. Poly(ADP-ribosyl)ation in regulation of chromatin structure and the DNA damage response. Chromosoma. 2014; 123(1-2):79-90. doi: 10.1007/s00412-013-0442-9 PMID: 24162931
9. Feng Z, Scott SP, Bussen W, Sharma GG, Guo G, Pandita TK, et al. Rad52 inactivation is synthetically lethal with BRCA2 deficiency. Proc Natl Acad Sci U S A. 2011; 108(2):686-91. PMID: 21148102 doi: 10.1073/pnas.1010959107
10. Cramer-Morales K, Nieborowska-Skorska M, Scheibner K, Padget M, Irvine DA, Sliwinski T, et al. Personalized synthetic lethality induced by targeting RAD52 in leukemias identified by gene mutation and expression profile. Blood. 2013; 122(7):1293-304. PMID: 23836560 doi: 10.1182/blood-2013-05-501072
11. Stark JM, Pierce AJ, Oh J, Pastink A, Jasin M. Genetic steps of mammalian homologous repair with distinct mutagenic consequences. Mol Cell Biol. 2004; 24(21):9305-16 PMID: 15485900
12. Baines IC, Colas P. Peptide aptamers as guides for small-molecule drug discovery. Drug Discov Today. 2006; 11(7-8):334-41. doi: S1359-6446(06)00008-0 PMID: 16580975
13. Kagawa W, Kurumizaka H, Ishitani R, Fukai S, Nureki O, Shibata T, et al. Crystal structure of the homologous-pairing domain from the human Rad52 recombinase in the undecameric form. Mol Cell. 2002; 10(2):359-71. doi: S1097276502005877 PMID: 12191481
14. Podszywalow-Bartnicka P, Wolczyk M, Kusio-Kobialka M, Wolanin K, Skowronek K, Nieborowska-Skorska M, et al. Downregulation of BRCA1 protein in BCR-ABL1 leukemia cells depends on stresstriggered TIAR-mediated suppression of translation. Cell Cycle. 2014; 13(23):3727-41. doi: 10.4161/15384101.2014.965013 PMID: 25483082
15. Gunn A, Stark JM. I-SceI-based assays to examine distinct repair outcomes of mammalian chromosomal double strand breaks. Methods Mol Biol. 2012; 920:379-91. Epub 2012/09/04. doi: 10.1007/978-1-61779-998-3-27 PMID: 22941618
16. Scully R, Ganesan S, Vlasakova K, Chen J, Socolovsky M, Livingston DM. Genetic analysis of BRCA1 function in a defined tumor cell line. Mol Cell. 1999; 4(6):1093-9. doi: S1097-2765(00)80238-5 PMID: 10635334
17. Irwin JJ, Shoichet BK, Mysinger MM, Huang N, Colizzi F, Wassam P, et al. Automated docking screens: a feasibility study. J Med Chem. 2009; 52(18):5712-20. doi: 10.1021/jm9006966 PMID: 19719084
18. Qin Z, Zhang J, Xu B, Chen L, Wu Y, Yang X, et al. Structure-based discovery of inhibitors of the YycG histidine kinase: new chemical leads to combat Staphylococcus epidermidis infections. BMC Microbiol. 2006; 6:96. doi: 1471-2180-6-96 PMID: 17094812
19. Vakana E, Altman JK, Glaser H, Donato NJ, Platanias LC. Antileukemic effects of AMPK activators on BCR-ABL-expressing cells. Blood. 2011; 118(24):6399-402. PMID: 22021366 doi: 10.1182/blood-2011-01-332783
20. Singleton MR, Wentzell LM, Liu Y, West SC, Wigley DB. Structure of the single-strand annealing domain of human RAD52 protein. Proc Natl Acad Sci U S A. 2002; 99(21):13492-7. doi: 10.1073/pnas. 212449899 PMID: 12370410
21. Kagawa W, Kagawa A, Saito K, Ikawa S, Shibata T, Kurumizaka H, et al. Identification of a second DNA binding site in the human Rad52 protein. J Biol Chem. 2008; 283(35):24264-73. PMID: 18593704 doi: 10.1074/jbc.M802204200
22. Corton JM, Gillespie JG, Hawley SA, Hardie DG. 5-Aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-Activated protein kinase in intact cells? Eur J Biochem. 1995; 229 (2):558-65. PMID: 7744080
23. Waring MJ. Lipophilicity in drug discovery. Expert Opin Drug Discov. 2013; 5(3):235-48. doi: 10.1517/17460441003605098 PMID: 22823020
24. Wang G, Wang Y, Wang L, Han L, Hou X, Fu H, et al. Design, synthesis and preliminary bioactivity studies of imidazolidine-2,4-dione derivatives as Bcl-2 inhibitors. Bioorg Med Chem. 2015; 23 (23):7359-65. doi: S0968-0896(15)30101-2 PMID: 26558516 doi: 10.1016/j.bmc.2015.10.023
25. Howie C, Suckling CJ, Woods HCS. Latent inhibitors. Part 6. Inhibition of dihydroorotate dehydrogenase by substituted 5-benzylhydantoins. J Chem Soc, Perkin Tans I. 1990; 11:3129-35.
26. Zimmermann MO, Lange A, Wilcken R, Cieslik MB, Exner TE, Joerger AC, et al. Halogen-enriched fragment libraries as chemical probes for harnessing halogen bonding in fragment-based lead discovery. Future Med Chem. 2014; 6(6):617-39. doi: 10.4155/fmc.14.20 PMID: 24895892
27. Wilcken R, Liu X, Zimmermann MO, Rutherford TJ, Fersht AR, Joerger AC, et al. Halogen-enriched fragment libraries as leads for drug rescue of mutant p53. J Am Chem Soc. 2012; 134(15):6810-8. doi: 10.1021/ja301056a PMID: 22439615
28. Tiefenbrunn T, Forli S, Happer M, Gonzalez A, Tsai Y, Soltis M, et al. Crystallographic fragment-based drug discovery: use of a brominated fragment library targeting HIV protease. Chem Biol Drug Des. 2014; 83(2):141-8. doi: 10.1111/cbdd.12227 PMID: 23998903
29. Chandramouly G, McDevitt S, Sullivan K, Kent T, Luz A, Glickman JF, et al. Small-Molecule Disruption of RAD52 Rings as a Mechanism for Precision Medicine in BRCA-Deficient Cancers. Chem Biol. 2015; 22(11):1491-504. doi: S1074-5521(15)00379-8 PMID: 26548611 doi: 10.1016/j.chembiol.2015.10.003