A small molecule that binds and inhibits the ETV1 transcription factor oncoprotein

Molecular Cancer Therapeutics

Volumn 13, Issue 6, 2014, Pages 1492-1502

  Pop, Marius S ^a,b   Stransky, Nicolas ^b,f   Garvie, Colin W ^b   Theurillat, Jean Philippe ^a,b   Hartman, Emily C ^b   Lewis, Timothy A ^b   Zhong, Cheng ^b   Culyba, Elizabeth K ^b   Lin, Fallon ^c   Daniels, Douglas S ^b   Pagliarini, Raymond ^c   Ronco, Lucienne ^b   Koehler, Angela N ^b,d,e   Garraway, Levi A ^a,b  

^a DANA FARBER CANCER INSTITUTE   (United States)

^b BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^c NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

^d Department of Biological Engineering ^*  (United States)

^e MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^f Blueprint Medicines   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,2,3 TRIAZINE DERIVATIVE; BRD 32048; ONCOPROTEIN; TRANSCRIPTION FACTOR ER81; UNCLASSIFIED DRUG; ANILINE DERIVATIVE; BRD32048; DNA BINDING PROTEIN; ETV1 PROTEIN, HUMAN; MOLECULAR LIBRARY; TRANSCRIPTION FACTOR; TRIAZINE DERIVATIVE;

ACETYLATION; ARTICLE; CONTROLLED STUDY; HUMAN; HUMAN CELL; MICROARRAY ANALYSIS; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN FUNCTION; TUMOR INVASION; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; GENE EXPRESSION REGULATION; MALE; METABOLISM; MOLECULAR LIBRARY; MOLECULARLY TARGETED THERAPY; NEOPLASMS; PATHOLOGY; PROMOTER REGION; PROSTATIC NEOPLASMS; SURFACE PLASMON RESONANCE; TUMOR CELL LINE;

ANILINE COMPOUNDS; CELL LINE, TUMOR; DNA-BINDING PROTEINS; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MALE; MOLECULAR TARGETED THERAPY; NEOPLASMS; PROMOTER REGIONS, GENETIC; PROSTATIC NEOPLASMS; SMALL MOLECULE LIBRARIES; SURFACE PLASMON RESONANCE; TRANSCRIPTION FACTORS; TRIAZINES;

EID: 84902664243     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-13-0689     Document Type: Article

References (50)

1. Hopkins AL, Groom CR. The druggable genome. Nat Rev Drug Discov 2002;1:727-30. (Pubitemid 37361545)
2. Boyd KE, Farnham PJ. Identification of target genes of oncogenic transcription factors. Proc Soc Exp Biol Med 1999;222:9-28.
3. Darnell JE Jr. Transcription factors as targets for cancer therapy. Nat Rev Cancer 2002;2:740-9.
4. Oh S, Shin S, Janknecht R. ETV1, 4 and 5: an oncogenic subfamily of ETS transcription factors. Biochim Biophys Acta 2012;1826:1-12.
5. Janknecht R. EWS-ETS oncoproteins: the linchpins of Ewing tumors. Gene 2005;363:1-14. (Pubitemid 41691887)
6. Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 2005;310:644-8. (Pubitemid 41528150)
7. Baca SC, Prandi D, Lawrence MS, Mosquera JM, Romanel A, Drier Y, et al. Punctuated evolution of prostate cancer genomes. Cell 2013;153:666-77.
8. Tomlins SA, Laxman B, Dhanasekaran SM, Helgeson BE, Cao X, Morris DS, et al. Distinct classes of chromosomal rearrangements create oncogenic ETS gene fusions in prostate cancer. Nature 2007;448:595-9. (Pubitemid 47206938)
9. Hermans KG, van der Korput HA, van Marion R, van de Wijngaart DJ, Ziel-van der Made A, Dits NF, et al. Truncated ETV1, fused to novel tissue-specific genes, and full-length ETV1 in prostate cancer. Cancer Res 2008;68:7541-9.
10. Jane-Valbuena J, Widlund HR, Perner S, Johnson LA, Dibner AC, Lin WM, et al. An oncogenic role for ETV1 in melanoma. Cancer Res 2010;70:2075-84.
11. Chi P, Chen Y, Zhang L, Guo X, Wongvipat J, Shamu T, et al. ETV1 is a lineage survival factor that cooperates with KIT in gastrointestinal stromal tumours. Nature 2010;467:849- 53.
12. Shin S, Kim TD, Jin F, van Deursen JM, Dehm SM, Tindall DJ, et al. Induction of prostatic intraepithelial neoplasia and modulation of androgen receptor by ETS variant 1/ETS-related protein 81. Cancer Res 2009;69:8102-10.
13. Baena E, Shao Z, Linn DE, Glass K, Hamblen MJ, Fujiwara Y, et al. ETV1 directs androgen metabolism and confers aggressive prostate cancer in targeted mice and patients. Genes Dev 2013;27:683-98.
14. Janknecht R. Regulation of the ER81 transcription factor and its coactivators by mitogen- and stress-activated protein kinase 1 (MSK1). Oncogene 2003;22:746-55. (Pubitemid 36269288)
15. Oh S, Shin S, Lightfoot SA, Janknecht R. 14-3-3 proteins modulate the ETS transcription factor ETV1 in prostate cancer. Cancer Res 2013;73:5110-9.
16. Goel A, Janknecht R. Concerted activation of ETS protein ER81 by p160 coactivators, the acetyltransferase p300 and the receptor tyrosine kinase HER2/Neu. J Biol Chem 2004;279:14909-16. (Pubitemid 38618881)
17. Bosc DG, Goueli BS, Janknecht R. HER2/Neu-mediated activation of the ETS transcription factor ER81 and its target gene MMP-1. Oncogene 2001;20:6215-24. (Pubitemid 32964434)
18. Fuchs B, Inwards CY, Janknecht R. Upregulation of the matrix metal-loproteinase- 1 gene by the Ewing's sarcoma associated EWS-ER81 and EWS-Fli-1 oncoproteins, c-Jun and p300. FEBS Lett 2003;553:104-8. (Pubitemid 37206333)
19. Vitari AC, Leong KG, Newton K, Yee C, O'Rourke K, Liu J, et al. COP1is a tumour suppressor that causes degradation of ETS transcription factors. Nature 2011;474:403-6.
20. Baert JL, Monte D, Verreman K, Degerny C, Coutte L, de Launoit Y. The E3 ubiquitin ligase complex component COP1 regulates PEA3 group member stability and transcriptional activity. Oncogene 2010;29: 1810-20.
21. Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, et al. Selective inhibition of BET bromodomains. Nature 2010;468:1067-73.
22. Rahim S, Beauchamp EM, Kong Y, Brown ML, Toretsky JA, Uren A. YK-4-279 inhibits ERG and ETV1 mediated prostate cancer cell invasion. PLoS ONE 2011;6:e19343.
23. Barber-Rotenberg JS, Selvanathan SP, Kong Y, Erkizan HV, Snyder TM, Hong SP, et al. Single enantiomer of YK-4-279 demonstrates specificity in targeting the oncogene EWS-FLI1. Oncotarget 2012;3:172- 82.
24. Clemons PA, Bodycombe NE, Carrinski HA, Wilson JA, Shamji AF, Wagner BK, et al. Small molecules of different origins have distinct distributions of structural complexity that correlate with protein-binding profiles. Proc Natl Acad Sci U S A 2010;107:18787-92.
25. Bradner JE, McPherson OM, Koehler AN. A method for the covalent capture and screening of diverse small molecules in a microarray format. Nat Protoc 2006;1:2344-52.
26. Bradner JE, McPherson OM, Mazitschek R, Barnes-Seeman D, Shen JP, Dhaliwal J, et al. A robust small-molecule microarray platform for screening cell lysates. Chem Biol 2006;13:493-504. (Pubitemid 43729507)
27. Miao H, Tallarico JA, Hayakawa H, Munger K, Duffner JL, Koehler AN, et al. Ring-opening and ring-closing reactions of a shikimic acid-derived substrate leading to diverse small molecules. J Comb Chem 2007;9:245-53.
28. Ng PY, Tang Y, Knosp WM, Stadler HS, Shaw JT. Synthesis of diverse lactam carboxamides leading to the discovery of a new transcription-factor inhibitor. Angew Chem Int Ed Engl 2007;46:5352-5. (Pubitemid 47067632)
29. Duffner JL, Clemons PA, Koehler AN. A pipeline for ligand discovery using small-molecule microarrays. Curr Opin Chem Biol 2007;11:74-82. (Pubitemid 46216129)
30. Petri Seiler K, Kuehn H, Pat Happ M, Decaprio D, Clemons PA. Using ChemBank to probe chemical biology. Curr Protoc Bioinformat 2008; Chapter 14:Unit 14 5.
31. Dai M, Wang P, Boyd AD, Kostov G, Athey B, Jones EG, et al. Evolving gene/transcript definitions significantly alter the interpretation of Gen-eChip data. Nucleic Acids Res 2005;33:e175.
32. Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, et al. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 2003;4:249-64.
33. Bolstad BM, Irizarry RA, Astrand M, Speed TP. A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 2003;19:185-93. (Pubitemid 36181903)
34. Wettenhall JM, Smyth GK. limmaGUI: a graphical user interface for linear modeling of microarray data. Bioinformatics 2004;20:3705-6. (Pubitemid 40136823)
35. Repesh LA. A new in vitro assay for quantitating tumor cell invasion. Invasion Metastasis 1989;9:192- 208.
36. Miyazaki I, Simizu S, Okumura H, Takagi S, Osada H. A small-molecule inhibitor shows that pirin regulates migration of melanoma cells. Nat Chem Biol 2010;6:667-73.
37. Seiler KP, George GA, Happ MP, Bodycombe NE, Carrinski HA, Norton S, et al. ChemBank: a small-molecule screening and cheminformatics resource database. Nucleic Acids Res 2008;36:D351-9. (Pubitemid 351149748)
38. Yasumoto K, Yokoyama K, Shibata K, Tomita Y, Shibahara S. Microphthalmia-associated transcription factor as a regulator for melano-cyte-specific transcription of the human tyrosinase gene. Mol Cell Biol 1994;14:8058-70. (Pubitemid 24373554)
39. Garraway LA, Widlund HR, Rubin MA, Getz G, Berger AJ, Ramaswamy S, et al. Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. Nature 2005;436:117-22. (Pubitemid 40966196)
40. Gewald R, Grunwald C, Egerland U. Discovery of triazines as potent, selective and orally active PDE4 inhibitors. Bioorg Med Chem Lett 2013;23:4308-14.
41. Mui EJ, Schiehser GA, Milhous WK, Hsu H, Roberts CW, Kirisits M, et al. Novel triazine JPC-2067-B inhibits Toxoplasma gondii in vitro and in vivo . PLoS Negl Trop Dis 2008;2:e190.
42. Venkatesan AM, Chen Z, dos Santos O, Dehnhardt C, Santos ED, Ayral-Kaloustian S, et al. PKI-179: an orally efficacious dual phospha-tidylinositol- 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor. Bioorg Med Chem Lett 2010;20:5869-73.
43. Wurz RP, Liu L, Yang K, Nishimura N, Bo Y, Pettus LH, et al. Synthesis and structure-activity relationships of dual PI3K/mTOR inhibitors based on a 4-amino-6-methyl-1,3,5-triazine sulfonamide scaffold. Bioorg Med Chem Lett 2012;22:5714-20.
44. Cai C, Hsieh CL, Omwancha J, Zheng Z, Chen SY, Baert JL, et al. ETV1 is a novel androgen receptor-regulated gene that mediates prostate cancer cell invasion. Mol Endocrinol 2007;21:1835-46. (Pubitemid 47173795)
45. Nhili R, Peixoto P, Depauw S, Flajollet S, Dezitter X, Munde MM, et al. Targeting the DNA-binding activity of the human ERG transcription factor using new heterocyclic dithiophene diamidines. Nucleic Acids Res 2013;41:125-38.
46. Goel A, Janknecht R. Acetylation-mediated transcriptional activation of the ETS protein ER81 by p300, P/CAF, and HER2/Neu. Mol Cell Biol 2003;23:6243- 54.
47. Kemp MM, Weiwer M, Koehler AN. Unbiased binding assays for discovering small-molecule probes and drugs. Bioorg Med Chem 2012;20:1979- 89.
48. Ong SE, Schenone M, Margolin AA, Li X, Do K, Doud MK, et al. Identifying the proteins to which small-molecule probes and drugs bind in cells. Proc Natl Acad Sci U S A 2009;106:4617-22.
49. Bowers EM, Yan G, Mukherjee C, Orry A, Wang L, Holbert MA, et al. Virtual ligand screening of the p300/CBP histone acetyltransferase: identification of a selective small molecule inhibitor. Chem Biol 2010;17:471- 82.
50. Czuwara-Ladykowska J, Sementchenko VI, Watson DK, Trojanowska M. Ets1 is an effector of the transforming growth factor beta (TGF-β) signaling pathway and an antagonist of the pro fibrotic effects of TGF-β. J Biol Chem 2002;277:20399-408. (Pubitemid 34967335)