Explorations of substituted urea functionality for the discovery of new activators of the heme-regulated inhibitor kinase

Journal of Medicinal Chemistry

Volumn 56, Issue 23, 2013, Pages 9457-9470

  Chen, Ting ^a   Takrouri, Khuloud ^a   Hee Hwang, Sung ^b   Rana, Sandeep ^c   Yefidoff Freedman, Revital ^a   Halperin, Jose ^a   Natarajan, Amarnath ^c   Morisseau, Christophe ^b   Hammock, Bruce ^b   Chorev, Michael ^a   Aktas, Bertal H ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIN; CYCLIN D1; GROWTH ARREST AND DNA DAMAGE INDUCIBLE PROTEIN 153; HEME REGULATED INHIBITOR KINASE; INITIATION FACTOR 2ALPHA; MESSENGER RNA; PHOSPHOTRANSFERASE; POLYCYCLIC AROMATIC HYDROCARBON DERIVATIVE; UNCLASSIFIED DRUG; UREA DERIVATIVE;

ADAPTATION; ANIMAL CELL; ARTICLE; BETA THALASSEMIA; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL STRESS; CYTOPLASMIC STRESS; DRUG POTENCY; DRUG SCREENING; DRUG SPECIFICITY; DRUG SYNTHESIS; ENZYME ACTIVATION; HUMAN; HUMAN CELL; NONHUMAN; PROTEIN PHOSPHORYLATION; STRUCTURE ACTIVITY RELATION;

EID: 84890449347     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm400793v     Document Type: Article

References (38)

1. Krishnamoorthy, T.; Pavitt, G. D.; Zhang, F.; Dever, T. E.; Hinnebusch, A. G. Tight binding of the phosphorylated alpha subunit of initiation factor 2 (eIF2alpha) to the regulatory subunits of guanine nucleotide exchange factor eIF2B is required for inhibition of translation initiation Mol. Cell. Biol. 2001, 21, 5018-5030
2. Kimball, S. R.; Fabian, J. R.; Pavitt, G. D.; Hinnebusch, A. G.; Jefferson, L. S. Regulation of guanine nucleotide exchange through phosphorylation of eukaryotic initiation factor eIF2alpha. Role of the alpha- and delta-subunits of eiF2b J. Biol. Chem. 1998, 273, 12841-1285
3. Harding, H. P.; Zhang, Y.; Bertolotti, A.; Zeng, H.; Ron, D. Perk is essential for translational regulation and cell survival during the unfolded protein response Mol. Cell 2000, 5, 897-904
4. Raven, J. F.; Koromilas, A. E. PERK and PKR: Old kinases learn new tricks Cell Cycle 2008, 7, 1146-1150
5. Baltzis, D.; Qu, L. K.; Papadopoulou, S.; Blais, J. D.; Bell, J. C.; Sonenberg, N.; Koromilas, A. E. Resistance to vesicular stomatitis virus infection requires a functional cross talk between the eukaryotic translation initiation factor 2alpha kinases PERK and PKR J. Virol. 2004, 78, 12747-12761
6. Dey, M.; Cao, C.; Dar, A. C.; Tamura, T.; Ozato, K.; Sicheri, F.; Dever, T. E. Mechanistic link between PKR dimerization, autophosphorylation, and eIF2alpha substrate recognition Cell 2005, 122, 901-913
7. Takada, Y.; Ichikawa, H.; Pataer, A.; Swisher, S.; Aggarwal, B. B. Genetic deletion of PKR abrogates TNF-induced activation of IkappaBalpha kinase, JNK, Akt and cell proliferation but potentiates p44/p42 MAPK and p38 MAPK activation Oncogene 2007, 26, 1201-1212
8. Cabanski, M.; Steinmuller, M.; Marsh, L. M.; Surdziel, E.; Seeger, W.; Lohmeyer, J. PKR regulates TLR2/TLR4-dependent signaling in murine alveolar macrophages Am. J. Respir. Cell Mol. Biol. 2008, 38, 26-31
9. Raven, J. F.; Baltzis, D.; Wang, S.; Mounir, Z.; Papadakis, A. I.; Gao, H. Q.; Koromilas, A. E. PKR and PKR-like endoplasmic reticulum kinase induce the proteasome-dependent degradation of cyclin D1 via a mechanism requiring eukaryotic initiation factor 2alpha phosphorylation J. Biol. Chem. 2008, 283, 3097-3108
10. Shi, Y.; Taylor, S. I.; Tan, S. L.; Sonenberg, N. When translation meets metabolism: multiple links to diabetes Endocr. Rev. 2003, 24, 91-101
11. Biason-Lauber, A.; Lang-Muritano, M.; Vaccaro, T.; Schoenle, E. J. Loss of kinase activity in a patient with Wolcott-Rallison syndrome caused by a novel mutation in the EIF2AK3 gene Diabetes 2002, 51, 2301-2305
12. Chen, J. J. Regulation of protein synthesis by the heme-regulated eIF2alpha kinase: Relevance to anemias Blood 2007, 109, 2693-2699
13. Chen, J. J. Heme-regulated eIF2α kinase. In Translational Control of Gene Expression; Sonenberg, N.; Hershey, J. W. B.; Mathews, M. B., Eds.; Cold Spring Harbor Laboratory Press: New York, 2000; pp 529-546.
14. Han, A. P.; Fleming, M. D.; Chen, J. J. Heme-regulated eIF2alpha kinase modifies the phenotypic severity of murine models of erythropoietic protoporphyria and beta-thalassemia J. Clin. Invest. 2005, 115, 1562-1570
15. Couturier, J.; Page, G.; Morel, M.; Gontier, C.; Claude, J.; Pontcharraud, R.; Fauconneau, B.; Paccalin, M. Inhibition of double-stranded RNA-dependent protein kinase strongly decreases cytokine production and release in peripheral blood mononuclear cells from patients with Alzheimer's disease J. Alzheimers Dis. 2010, 21, 1217-1231
16. Donze, O.; Jagus, R.; Koromilas, A. E.; Hershey, J. W.; Sonenberg, N. Abrogation of translation initiation factor eIF-2 phosphorylation causes malignant transformation of NIH 3T3 cells EMBO J. 1995, 14, 3828-3834
17. Berns, A. A tRNA with oncogenic capacity Cell 2008, 133, 29-30
18. Marshall, L.; Kenneth, N. S.; White, R. J. Elevated tRNA(iMet) synthesis can drive cell proliferation and oncogenic transformation Cell 2008, 133, 78-89
19. Dever, T. E.; Yang, W.; Astrom, S.; Bystrom, A. S.; Hinnebusch, A. G. Modulation of tRNA(iMet), eIF-2, and eIF-2B expression shows that GCN4 translation is inversely coupled to the level of eIF-2·GTP·Met- tRNA(iMet) ternary complexes Mol. Cell. Biol. 1995, 15, 6351-6363
20. 2+ stores, phosphorylation of eIF2alpha, and sustained inhibition of translation initiation mediate the anticancer effects of clotrimazole Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 8280-8285
21. Aktas, B. H.; Qiao, Y.; Ozdelen, E.; Schubert, R.; Sevinc, S.; Harbinski, F.; Grubissich, L.; Singer, S.; Halperin, J. A. Small-molecule targeting of translation initiation for cancer therapy Oncotarget 2013, 4, 1606-1617
22. Bai, H.; Chen, T.; Ming, J.; Sun, H.; Cao, P.; Fusco, D. N.; Chung, R. T.; Chorev, M.; Jin, Q.; Aktas, B. H. Dual activators of protein kinase R (PKR) and protein kinase R-like kinase PERK identify common and divergent catalytic targets ChemBioChem 2013, 14, 1255-1262
23. Denoyelle, S.; Chen, T.; Yang, H.; Chen, L.; Zhang, Y.; Halperin, J. A.; Aktas, B. H.; Chorev, M. Synthesis and SAR study of novel 3,3-diphenyl-1,3- dihydroindol-2-one derivatives as potent eIF2·GTP·Met-tRNA ternary complex inhibitors Eur. J. Med. Chem. 2013, 69C, 537-553
24. Chen, L.; Aktas, B. H.; Wang, Y.; He, X.; Sahoo, R.; Zhang, N.; Denoyelle, S.; Kabha, E.; Yang, H.; Freedman, R. Y.; Supko, J. G.; Chorev, M.; Wagner, G.; Halperin, J. A. Tumor suppression by small molecule inhibitors of translation initiation Oncotarget 2012, 3, 869-881
25. Chen, T.; Ozel, D.; Qiao, Y.; Harbinski, F.; Chen, L.; Denoyelle, S.; He, X.; Zvereva, N.; Supko, J. G.; Chorev, M.; Halperin, J. A.; Aktas, B. H. Chemical genetics identify eIF2alpha kinase heme-regulated inhibitor as an anticancer target Nat. Chem. Biol. 2011, 7, 610-616
26. Denoyelle, S.; Chen, T.; Chen, L.; Wang, Y.; Klosi, E.; Halperin, J. A.; Aktas, B. H.; Chorev, M. In vitro inhibition of translation initiation by N,N′-diarylureas-potential anti-cancer agents Bioorg. Med. Chem. Lett. 2012, 22, 402-409
27. Morisseau, C.; Hammock, B. D. Impact of soluble epoxide hydrolase and epoxyeicosanoids on human health Annu. Rev. Pharmacol. Toxicol. 2013, 53, 37-58
28. Shen, H. C.; Hammock, B. D. Discovery of inhibitors of soluble epoxide hydrolase: A target with multiple potential therapeutic indications J. Med. Chem. 2012, 55, 1789-1808
29. Scherman, M. S.; North, E. J.; Jones, V.; Hess, T. N.; Grzegorzewicz, A. E.; Kasagami, T.; Kim, I. H.; Merzlikin, O.; Lenaerts, A. J.; Lee, R. E.; Jackson, M.; Morisseau, C.; McNeil, M. R. Screening a library of 1600 adamantyl ureas for anti-Mycobacterium tuberculosis activity in vitro and for better physical chemical properties for bioavailability Bioorg. Med. Chem. 2012, 20, 3255-3262
30. Hwang, S. H.; Morisseau, C.; Do, Z.; Hammock, B. D. Solid-phase combinatorial approach for the optimization of soluble epoxide hydrolase inhibitors Bioorg. Med. Chem. Lett. 2006, 16, 5773-5777
31. Madar, D. J.; Djuric, S. W.; Michmerhuizen, M. J.; Kopecka, H. A.; Li, X.; Longenecker, K. L.; Pei, Z.; Pireh, D.; Sham, H. L.; Stewart, K. D.; Szczepankiewicz, B. G.; Wiedeman, P. E.; Yong, H. Pharmaceutical compositions as inhibitors of dipeptidyl peptidase-IV (DPP-IV). U.S. Patent 20050215784 A1, 2005.
32. Ziegeler, G.; Ming, J.; Koseki, J. C.; Sevinc, S.; Chen, T.; Ergun, S.; Qin, X.; Aktas, B. H. Embryonic lethal abnormal vision-like HuR-dependent mRNA stability regulates post-transcriptional expression of cyclin-dependent kinase inhibitor p27Kip1 J. Biol. Chem. 2010, 285, 15408-15419
33. Palakurthi, S. S.; Fluckiger, R.; Aktas, H.; Changolkar, A. K.; Shahsafaei, A.; Harneit, S.; Kilic, E.; Halperin, J. A. Inhibition of translation initiation mediates the anticancer effect of the n-3 polyunsaturated fatty acid eicosapentaenoic acid Cancer Res. 2000, 60, 2919-2925
34. Sheppard, C. W. The effect of fluorine substitution on the electronic properties of alkoxy, alkylthio and alkylsulfonyl groups J. Am. Chem. Soc. 1963, 85, 1314-1318
35. Haas, A. The element displacement principle: A new guide in p-block element chemistry Adv. Inorg. Radiochem. 1984, 28, 167-202
36. O'Hagan, D. Understanding organofluorine chemistry. An introduction to the C-F bond Chem. Soc. Rev. 2008, 37, 308-319
37. Hwang, S. H.; Tsai, H. J.; Liu, J. Y.; Morisseau, C.; Hammock, B. D. Orally bioavailable potent soluble epoxide hydrolase inhibitors J. Med. Chem. 2007, 50, 3825-3840
38. Aktas, H.; Cai, H.; Cooper, G. M. Ras links growth factor signaling to the cell cycle machinery via regulation of cyclin D1 and the Cdk inhibitor p27KIP1 Mol. Cell. Biol. 1997, 17, 3850-3857