Diverse Small Molecule Inhibitors of Human Apurinic/Apyrimidinic Endonuclease APE1 Identified from a Screen of a Large Public Collection

PLoS ONE

Volumn 7, Issue 10, 2012, Pages

  Dorjsuren, Dorjbal ^a   Kim, Daemyung ^c   Vyjayanti, Vaddadi N ^b   Maloney, David J ^a   Jadhav, Ajit ^a   Wilson II, David M ^b   Simeonov, Anton ^a  

^a NATIONAL INSTITUTES OF HEALTH   (United States)

^b NATIONAL INSTITUTE ON AGING   (United States)

^c Chongju University   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

APURINIC APYRIMIDINIC ENDONUCLEASE 1; DNA (APURINIC OR APYRIMIDINIC SITE) LYASE; ENZYME INHIBITOR; MLS 000088142; MLS 000090966; MLS 000092582; MLS 000107874; MLS 000115025; MLS 000391557; MLS 000419194; MLS 000551724; MLS 000563483; MLS 000587064; MLS 000594187; MLS 000677191; MLS 000723827; MLS 000737267; MLS 000763226; MLS 000778639; MLS 000863573; MLS 000877008; MLS 000974674; MLS 001076862; MLS 001090278; MLS 001105846; MLS 001196838; MLS 001217741; MLS 001306480; MLS 002252117; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ARTICLE; CONCENTRATION RESPONSE; DRUG MECHANISM; DRUG STRUCTURE; ENZYME INHIBITION; GENOTOXICITY; HIGH THROUGHPUT SCREENING; MOLECULAR LIBRARY; QUANTITATIVE ANALYSIS;

CELL SURVIVAL; DNA DAMAGE; DNA REPAIR; DNA-(APURINIC OR APYRIMIDINIC SITE) LYASE; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; HELA CELLS; HUMANS; METHYL METHANESULFONATE; MOLECULAR STRUCTURE; SMALL MOLECULE LIBRARIES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84867860667     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0047974     Document Type: Article

References (54)

1. Bapat A, Fishel M, Kelley MR, (2009) Going Ape as an Approach to Cancer Therapeutics. Antioxid Redox Signal 11: 651-668.
2. Kulkarni A, Wilson DM 3rd, (2008) The involvement of DNA-damage and-repair defects in neurological dysfunction. Am J Hum Genet 82: 539-566.
3. Fortini P, Pascucci B, Parlanti E, D'Errico M, Simonelli V, et al. (2003) The base excision repair: mechanisms and its relevance for cancer susceptibility. Biochimie 85: 1053-1071.
4. Abbotts R, Madhusudan S, (2010) Human AP endonuclease 1 (APE1): from mechanistic insights to druggable target in cancer. Cancer Treat Rev 36: 425-435.
5. Barnes DE, Lindahl T, (2004) Repair and genetic consequences of endogenous DNA base damage in mammalian cells. Annu Rev Genet 38: 445-476.
6. Karran P, Offman J, Bignami M, (2003) Human mismatch repair, drug-induced DNA damage, and secondary cancer. Biochimie 85: 1149-1160.
7. Cleaver JE, (2005) Cancer in xeroderma pigmentosum and related disorders of DNA repair. Nat Rev Cancer 5: 564-573.
8. Helleday T, Petermann E, Lundin C, Hodgson B, Sharma RA, (2008) DNA repair pathways as targets for cancer therapy. Nat Rev Cancer 8: 193-204.
9. Powell SN, Bindra RS, (2009) Targeting the DNA damage response for cancer therapy. DNA Repair (Amst) 8: 1153-1165.
10. Sharma RA, Dianov GL, (2007) Targeting base excision repair to improve cancer therapies. Mol Aspects Med 28: 345-374.
11. Wilson DM 3rd, Barsky D, (2001) The major human abasic endonuclease: formation, consequences and repair of abasic lesions in DNA. Mutat Res 485: 283-307.
12. Fung H, Demple B, (2005) A vital role for Ape1/Ref1 protein in repairing spontaneous DNA damage in human cells. Mol Cell 17: 463-470.
13. Izumi T, Brown DB, Naidu CV, Bhakat KK, Macinnes MA, et al. (2005) Two essential but distinct functions of the mammalian abasic endonuclease. Proc Natl Acad Sci U S A 102: 5739-5743.
14. Fishel ML, Kelley MR, (2007) The DNA base excision repair protein Ape1/Ref-1 as a therapeutic and chemopreventive target. Mol Aspects Med 28: 375-395.
15. McNeill DR, Wilson DM 3rd, (2007) A dominant-negative form of the major human abasic endonuclease enhances cellular sensitivity to laboratory and clinical DNA-damaging agents. Mol Cancer Res 5: 61-70.
16. McNeill DR, Lam W, DeWeese TL, Cheng YC, Wilson DM, 3rd (2009) Impairment of APE1 function enhances cellular sensitivity to clinically relevant alkylators and antimetabolites. Mol Cancer Res 7: 897-906.
17. Ashworth A, (2008) A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair. J Clin Oncol 26: 3785-3790.
18. Sultana R, McNeill DR, Abbotts R, Mohammed MZ, Zdzienicka MZ, et al. (2012) Synthetic lethal targeting of DNA double-strand break repair deficient cells by human apurinic/apyrimidinic endonuclease inhibitors. Int J Cancer in press: n/a-n/a.
19. Madhusudan S, Smart F, Shrimpton P, Parsons JL, Gardiner L, et al. (2005) Isolation of a small molecule inhibitor of DNA base excision repair. Nucleic Acids Res 33: 4711-4724.
20. Seiple LA, Cardellina JH 2nd, Akee R, Stivers JT, (2008) Potent inhibition of human apurinic/apyrimidinic endonuclease 1 by arylstibonic acids. Mol Pharmacol 73: 669-677.
21. Simeonov A, Kulkarni A, Dorjsuren D, Jadhav A, Shen M, et al. (2009) Identification and characterization of inhibitors of human apurinic/apyrimidinic endonuclease APE1. PLoS ONE 4: e5740.
22. Zawahir Z, Dayam R, Deng J, Pereira C, Neamati N, (2009) Pharmacophore guided discovery of small-molecule human apurinic/apyrimidinic endonuclease 1 inhibitors. J Med Chem 52: 20-32.
23. Bapat A, Glass LS, Luo M, Fishel ML, Long EC, et al. (2010) Novel small molecule inhibitor of Ape1 endonuclease blocks proliferation and reduces viability of glioblastoma cells. J Pharmacol Exp Ther 334: 988-998.
24. Wilson III DM, Simeonov A, (2010) Small molecule inhibitors of DNA repair nuclease activities of APE1. Cell Mol Life Sci 67: 3621-3631.
25. Inglese J, Auld DS, Jadhav A, Johnson RL, Simeonov A, et al. (2006) Quantitative high-throughput screening: a titration-based approach that efficiently identifies biological activities in large chemical libraries. Proc Natl Acad Sci U S A 103: 11473-11478.
26. Yasgar A, Shinn P, Jadhav A, Auld D, Michael S, et al. (2008) Compound Management for Quantitative High-Throughput Screening. JALA Charlottesv Va 13: 79-89.
27. Inglese J, Johnson RL, Simeonov A, Xia M, Zheng W, et al. (2007) High-throughput screening assays for the identification of chemical probes. Nat Chem Biol 3: 466-479.
28. Michael S, Auld D, Klumpp C, Jadhav A, Zheng W, et al. (2008) A robotic platform for quantitative high-throughput screening. Assay Drug Dev Technol 6: 637-657.
29. Hill AV (1910) The possible effects of the aggregation of the molecule of haemoglobin on its dissociation curves. J Physiol(London). 4-7.
30. Roberts G, Myatt GJ, Johnson WP, Cross KP, Blower PE Jr, (2000) LeadScope: software for exploring large sets of screening data. J Chem Inf Comput Sci 40: 1302-1314.
31. Wilson DM, 3rd, Takeshita M, Grollman AP, Demple B (1995) Incision activity of human apurinic endonuclease (Ape) at abasic site analogs in DNA. J Biol Chem 270: 16002-16007.
32. Wilson DM, 3rd (2005) Ape1 abasic endonuclease activity is regulated by magnesium and potassium concentrations and is robust on alternative DNA structures. J Mol Biol 345: 1003-1014.
33. Zhang JH, Chung TD, Oldenburg KR, (1999) A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays. J Biomol Screen 4: 67-73.
34. Eastwood BJ, Farmen MW, Iversen PW, Craft TJ, Smallwood JK, et al. (2006) The Minimum Significant Ratio: A Statistical Parameter to Characterize the Reproducibility of Potency Estimates from Concentration-Response Assays and Estimation by Replicate-Experiment Studies. J Biomol Screen 11: 253-261.
35. Jadhav A, Ferreira R, Klumpp C, Mott BT, Austin C, et al. (2010) Quantitative Analyses of Aggregation, Autofluorescence, and Reactivity Artifacts in a Screen for Inhibitors of a Thiol Protease J Med Chem. 53: 37-51.
36. Erzberger JP, Barsky D, Scharer OD, Colvin ME, Wilson DM 3rd, (1998) Elements in abasic site recognition by the major human and Escherichia coli apurinic/apyrimidinic endonucleases. Nucl Acids Res 26: 2771-2778.
37. Mol CD, Hosfield DJ, Tainer JA, (2000) Abasic site recognition by two apurinic/apyrimidinic endonuclease families in DNA base excision repair: the 3' ends justify the means. Mutat Res 460: 211-229.
38. Heyduk T, Heyduk E, (2002) Molecular beacons for detecting DNA binding proteins. Nat Biotechnol 20: 171-176.
39. Lea WL, Simeonov A, (2011) Fluorescence Polarization Assays in Small Molecule Screening. Expert Op Drug Disc 6: 17-32.
40. Wyatt MD, Pittman DL, (2006) Methylating agents and DNA repair responses: Methylated bases and sources of strand breaks. Chem Res Toxicol 19: 1580-1594.
41. Chou T-C, (2006) Theoretical Basis, Experimental Design, and Computerized Simulation of Synergism and Antagonism in Drug Combination Studies. Pharmacological Reviews 58: 621-681.
42. Auparakkitanon S, Chapoomram S, Kuaha K, Chirachariyavej T, Wilairat P, (2006) Targeting of hematin by the antimalarial pyronaridine. Antimicrob Agents Chemother 50: 2197-2200.
43. Naidu MD, Agarwal R, Pena LA, Cunha L, Mezei M, et al. (2011) Lucanthone and Its Derivative Hycanthone Inhibit Apurinic Endonuclease-1 (APE1) by Direct Protein Binding. PLoS ONE 6: e23679.
44. Shimozono N, Wada H, Biotech S (2004) Substituted Isoxazole Alkylamine Derivative and Agri- and Horticultural Fungicide. WO/2003/074501.
45. Rai G, Vyjayanti VN, Dorjsuren D, Simeonov A, Jadhav A, et al. (2012) Synthesis, Biological Evaluation, and Structure-Activity Relationships of a Novel Class of Apurinic/Apyrimidinic Endonuclease 1 Inhibitors. J Med Chem 55: 3101-3112.
46. Hong H, Neamati N, Winslow HE, Christensen JL, Orr A, et al. (1998) Identification of HIV-1 integrase inhibitors based on a four-point pharmacophore. Antivir Chem Chemother 9: 461-472.
47. Hwang JS, Lee SA, Hong SS, Han XH, Lee C, et al. (2010) Phenanthrenes from Dendrobium nobile and their inhibition of the LPS-induced production of nitric oxide in macrophage RAW 264.7 cells. Bioorg Med Chem Lett 20: 3785-3787.
48. Sun W, Cama LD, Birzin ET, Warrier S, Locco L, et al. (2006) 6H-Benzo[c]chromen-6-one derivatives as selective ERbeta agonists. Bioorg Med Chem Lett 16: 1468-1472.
49. Bowers EM, Yan G, Mukherjee C, Orry A, Wang L, et al. (2010) Virtual ligand screening of the p300/CBP histone acetyltransferase: identification of a selective small molecule inhibitor. Chem Biol 17: 471-482.
50. Wang L, Gural A, Sun XJ, Zhao X, Perna F, et al. (2011) The leukemogenicity of AML1-ETO is dependent on site-specific lysine acetylation. Science 333: 765-769.
51. Walensky LD, Stewart ML, Cohen N, Institute D-FCR (2011) Small Molecules for the Modulation of MCL-1 and Methods for Modulating Cell Death, Cell Division, Cell Differentiation, and Methods of Treating Disorders. WPO, WO/2011/094708.
52. Xia G, Benmohamed R, Kim J, Arvanites AC, Morimoto RI, et al. (2011) Pyrimidine-2,4,6-trione Derivatives and Their Inhibition of Mutant SOD1-Dependent Protein Aggregation. Toward a Treatment for Amyotrophic Lateral Sclerosis. J Med Chem 54: 2409-2421.
53. Screpanti E, Santaguida S, Nguyen T, Silvestri R, Gussio R, et al. (2010) A Screen for Kinetochore-Microtubule Interaction Inhibitors Identifies Novel Antitubulin Compounds. PLoS ONE 5: e11603.
54. Rishton GM, (1997) Reactive compounds and in vitro false positives in HTS. Drug Discovery Today 2: 382-384.