The Cambridge Crystallographic Data Center; 12, Union Street, Cambridge, CB2 1EZ, UK: [Google Scholar] 27. could come with an inflationary influence on the IC50 values obtained with this assay when testing substrate competitive compounds. non-etheless, this finding establishes that compound BI-87G3 can function within a cellular context. Open in another window Figure 4 TR-FRET analysis of c-Jun phosphorylation upon TNF-alpha stimulation of HeLa cells in the current presence of increasing 87G3. To conclude, we created a fresh group of JNK inhibitors effectively, many of that are potent in vitro. Our results indicate that targeting the proteinCprotein interaction between JNK and JIP with a little molecule is a fresh and promising avenue for JNK related therapeutics. Acknowledgments We gratefully acknowledge financial support in the NIH (Grants # DK073274 and “type”:”entrez-nucleotide”,”attrs”:”text”:”DK080263″,”term_id”:”187584901″DK080263) and Syndexa pharmaceuticals (to M.P.). Notes and References 1. Manning G. Science. 2002;298:1912. [PubMed] [Google Scholar] 2. Manning AM, Davis RJ. Nat. Rev. Drug Discovery. 2003;2:554. [PubMed] [Google Scholar] 3. Bogoyevitch MA. Trends Mol. Med. 2005;11:232. [PubMed] [Google Scholar] 4. Gupta S, Barrett T, Whitmarsh AJ, Cavanagh J, Sluss HK, Drijard B, Davis RJ. EMBO J. 1996;15:2760. [PMC free article] [PubMed] [Google Scholar] 5. Kyriakis JM, Avruch J. Physiol. Rev. 2001;81:807. [PubMed] [Google Scholar] 6. Pearson G, Robinson R, Gibson TB, Xu BE, Karandikar M, Berman K, Cobb MH. Endocr. Rev. 2001;22:153. [PubMed] [Google Scholar] 7. Kallunki T, Deng T, Hibi M, Karin M. Cell. 1996;87:929. [PubMed] [Google Scholar] 8. Yang S-H, Whitmarsh AJ, Davis RJ, Sharrocks AD. EMBO J. 1998;17:1740. [PMC free article] [PubMed] [Google Scholar] 9. Barr RK, Kendrick TS, Bogoyevitch MA. J. Biol. Chem. 2002;277:10987. [PubMed] [Google Scholar] 10. Bonny C, Oberson A, Negri S, Sauser C, Schorderet DF. Diabetes. 2001;50:77. [PubMed] [Google Scholar] 11. Dickens M, Roger JS, Cavanagh J, Raitano A, Xia Z, Halpern JR, Greenberg ME, Sawyers CL, Davis RJ. Science. 1997;277:693. [PubMed] [Google Scholar] 12. Heo Y-S, Kim S-K, Seo CI, Kim Y-K, Sung B-J, Lee HS, Lee JI, Park S-Y, Kim JH, Hwang KY, Hyun Y-L, Jeon YH, Ro S, Cho JM, Lee TG, Yang C-H. EMBO J. 2004;23:2185. [PMC free article] [PubMed] [Google Scholar] 13. Kaneto H, Nakatani Y, Miyatsuka T, Kawamori D, Matsuoka T, Matsuhisa M, Kajimoto Y, Ichijo H, Yamasaki Y, Hori M. Nat. Med. 2004;10:1128. [PubMed] [Google Scholar] 14. Swahn B-M, Xue Y, Arzel E, Kallin E, Magnus A, Plobeck N, Viklund J. Bioorg. Med. Chem. Lett. 2006;16:1397. [PubMed] [Google Scholar] 15. Graczyk PP, Khan A, Bhatia GS, Palmer V, Medland D, Numata H, Oinuma H, Catchick J, Dunne A, Ellis M, Smales C, Whitfield J, Neame SJ, Shah B, Wilton D, Morgan L, Patel T, Chung R, Desmond H, Staddon JM, Sato N, Inoue A. Bioorg. Med. Chem. Lett. 2005;15:4666. [PubMed] [Google Scholar] 16. Gaillard P, Jeanclaude-Etter I, Ardissone V, Arkinstall S, Cambet Y, Camps M, Chabert C, Church D, Cirillo R, Gretener D, Halazy S, Nichols A, Szyndralewiez C, Vitte P-A, Gotteland J-P. J. Med. Chem. 2005;48:4596. [PubMed] [Google Scholar] 17. Szczepankiewicz BG, Kosogof C, Nelson LTJ, Liu G, Liu B, Zhao H, Serby MD, Xin Z, Liu M, Gum RJ, Haasch DL, Wang S, Clampit JE, Johnson EF, Lubben TH, Stashko MA, Olejniczak ET, Sun C, Dorwin SA, Haskins K, Abad-Zapatero C, Fry EH, Hutchins CW, Sham HL, Rondinone CM, Trevillyan JM. J. Med. Chem. 2006;49:3563. [PubMed] [Google Scholar] 18. Swahn B-M, Huerta F, Kallin E, Malmstr?m J, Weigelt T, Viklund J, Womack P, Xue Y, ?hberg L. Bioorg. Med. Chem. Lett. 2005;15:5095. [PubMed] [Google Scholar] 19. Rckle T, Biamonte M, Grippi-Vallotton T, Arkinstall S, Cambet Y, Camps M, Chabert C, Church DJ, Halazy S, Jiang X, Martinou I, Nichols A, Sauer W, Gotteland J-P. J. Med. Chem. 2004;47:6921. [PubMed] [Google Scholar] 20. Bennett BL, Sasaki DT, Murray BW, O’Leary EC, Sakata ST, Xu W, JC Leisten, Motiwala A, Pierce S, Satoh Y, Bhagwat SS, Manning AM, Anderson DW. Proc. Natl. Acad. Sci. 2001;98:13681. [PMC free article] [PubMed] [Google Scholar] 21. Teague SJ, Barber S, King S, Stein L. Tetrahedron Lett. 2005;46:4613. [Google Scholar] 22. Vazquez J, De SK, Chen L-H, Riel-Mehan M, Emdadi A, Cellitti J,.The medium was then removed by aspiration as well as the cells were lysed with the addition of 20 ll of lysis buffer (20 mM TRIS-HCl pH 7.6, 5 mM EDTA, 1% NP-40 substitute, 5 mM NaF, 150 mM NaCl, 1:100 protease and phosphatase inhibitor mix, SIGMA P8340 and P2850, respectively). finding establishes that compound BI-87G3 can function within a cellular context. Open in another window Figure 4 TR-FRET analysis of c-Jun phosphorylation upon TNF-alpha stimulation of HeLa cells in the current presence of increasing 87G3. To conclude, we successfully developed a fresh group of JNK inhibitors, a lot of that are potent in vitro. Our results indicate that targeting the proteinCprotein interaction between JNK and JIP with a little molecule is a fresh and promising avenue for JNK related therapeutics. Acknowledgments We gratefully acknowledge financial support in the NIH (Grants # DK073274 and “type”:”entrez-nucleotide”,”attrs”:”text”:”DK080263″,”term_id”:”187584901″DK080263) and Syndexa pharmaceuticals (to M.P.). References and notes 1. Manning G. Science. 2002;298:1912. [PubMed] [Google Scholar] 2. Manning AM, Davis RJ. Nat. Rev. Drug Discovery. 2003;2:554. [PubMed] [Google Scholar] 3. Bogoyevitch MA. Trends Mol. Med. 2005;11:232. [PubMed] [Google Scholar] 4. Gupta S, Barrett T, Whitmarsh AJ, Cavanagh J, Sluss HK, Drijard B, Davis RJ. EMBO J. 1996;15:2760. [PMC free article] [PubMed] [Google Scholar] 5. Kyriakis JM, Avruch J. Physiol. Rev. 2001;81:807. [PubMed] [Google Scholar] 6. Pearson G, Robinson R, Gibson TB, Xu BE, Karandikar M, Berman K, Cobb MH. Endocr. Rev. 2001;22:153. [PubMed] [Google Scholar] 7. Kallunki T, Deng T, Hibi M, Karin M. Cell. 1996;87:929. [PubMed] [Google Scholar] 8. Yang S-H, Whitmarsh AJ, Davis RJ, Sharrocks AD. EMBO J. 1998;17:1740. [PMC free article] [PubMed] [Google Scholar] 9. Barr RK, Kendrick TS, Bogoyevitch MA. J. Biol. Chem. 2002;277:10987. [PubMed] [Google Scholar] 10. Bonny C, Oberson A, Negri S, Sauser C, Schorderet DF. Diabetes. 2001;50:77. [PubMed] [Google Scholar] 11. Dickens M, Roger JS, Cavanagh J, Raitano A, Xia Z, Halpern JR, Greenberg ME, Sawyers CL, Davis RJ. Science. 1997;277:693. [PubMed] [Google Scholar] 12. Corin Heo Y-S, Kim S-K, Seo CI, Kim Y-K, Sung B-J, Lee HS, Lee JI, Park S-Y, Kim JH, Hwang KY, Hyun Y-L, Jeon YH, Ro S, Cho JM, Lee TG, Yang C-H. EMBO J. 2004;23:2185. [PMC free article] [PubMed] [Google Scholar] 13. Kaneto H, Nakatani Y, Miyatsuka T, Kawamori D, Matsuoka T, Matsuhisa M, Kajimoto Y, Ichijo H, Yamasaki Y, Hori M. Nat. Med. 2004;10:1128. [PubMed] [Google Scholar] 14. Swahn B-M, Xue Y, Arzel E, Kallin E, Magnus A, Plobeck N, Viklund J. Bioorg. Med. Chem. Lett. 2006;16:1397. [PubMed] [Google Scholar] 15. Graczyk PP, Khan A, Bhatia GS, Palmer V, Medland D, Numata H, Oinuma H, Catchick J, Dunne A, Ellis M, Smales C, Whitfield J, Neame SJ, Shah B, Wilton D, Morgan L, Patel T, Chung R, Desmond H, Staddon JM, Sato N, Inoue A. Bioorg. Med. Chem. Lett. 2005;15:4666. [PubMed] [Google Scholar] 16. Gaillard P, Jeanclaude-Etter I, Ardissone V, Arkinstall S, Cambet Y, Camps M, Chabert C, Church D, Cirillo R, Gretener D, Halazy S, Nichols A, Szyndralewiez C, Vitte P-A, Gotteland J-P. J. Med. Chem. 2005;48:4596. [PubMed] [Google Scholar] 17. Szczepankiewicz BG, Kosogof C, Nelson LTJ, Liu G, Liu B, Zhao H, Serby MD, Xin Z, Liu M, Gum RJ, Haasch DL, Wang S, Clampit JE, Johnson EF, Lubben TH, Stashko MA, Olejniczak ET, Sun C, Dorwin SA, Haskins K, Abad-Zapatero C, Fry EH, Hutchins CW, Sham HL, Rondinone CM, Trevillyan JM. J. Med. Chem. 2006;49:3563. [PubMed] [Google Scholar] 18. Swahn B-M, Huerta F, Kallin E, Malmstr?m J, Weigelt T, Viklund J, Womack P, Xue Y, ?hberg L. Bioorg. Med. Chem. Lett. 2005;15:5095. [PubMed] [Google Scholar] 19. Rckle T, Biamonte M, Grippi-Vallotton T, Arkinstall S, Cambet Y, Camps M, Chabert C, Church DJ, Halazy S, Jiang X, Martinou I, Nichols A, Sauer W, Gotteland J-P. J. Med. Chem. 2004;47:6921. [PubMed] [Google Scholar] 20. Bennett BL, Sasaki DT, Murray BW, O’Leary EC, Sakata ST, Xu W, Leisten JC, Motiwala A, Pierce S, Satoh Y, Bhagwat SS, Manning AM, Anderson DW. Proc. Natl. Acad. Sci. 2001;98:13681. [PMC free article] [PubMed] [Google Scholar] 21. Teague SJ, Barber S, King S, Stein L. Tetrahedron Lett. 2005;46:4613. [Google Scholar] 22. Vazquez J, De SK, Chen L-H, Riel-Mehan M, Emdadi.[PubMed] [Google Scholar] 16. in the current presence of increasing 87G3. To conclude, we successfully created a new group of JNK inhibitors, a lot of which are powerful in vitro. Our outcomes indicate that concentrating on the proteinCprotein connections between JNK and JIP with a little molecule is a fresh and appealing avenue for JNK related therapeutics. Acknowledgments We gratefully acknowledge economic support in the NIH (Grants or loans # DK073274 and “type”:”entrez-nucleotide”,”attrs”:”text”:”DK080263″,”term_id”:”187584901″DK080263) and Syndexa pharmaceuticals (to M.P.). Personal references and records 1. Manning G. Research. 2002;298:1912. [PubMed] [Google Scholar] 2. Manning AM, Davis RJ. Nat. Rev. Medication Breakthrough. 2003;2:554. [PubMed] [Google Scholar] 3. Bogoyevitch MA. Tendencies Mol. Med. 2005;11:232. [PubMed] [Google Scholar] 4. Gupta S, Barrett T, Whitmarsh AJ, Cavanagh J, Sluss HK, Drijard B, Davis RJ. EMBO J. 1996;15:2760. [PMC free of charge content] [PubMed] [Google Scholar] 5. Kyriakis JM, Avruch J. Physiol. Rev. 2001;81:807. [PubMed] [Google Scholar] 6. Pearson G, Robinson R, Gibson TB, Xu End up being, Karandikar M, Berman K, Cobb MH. Endocr. Rev. 2001;22:153. [PubMed] [Google Scholar] 7. Kallunki T, Deng T, Hibi M, Karin M. Cell. 1996;87:929. [PubMed] [Google Scholar] 8. Yang S-H, Whitmarsh AJ, Davis RJ, Sharrocks Advertisement. EMBO J. 1998;17:1740. [PMC free of charge content] [PubMed] [Google Scholar] 9. Barr RK, Kendrick TS, Bogoyevitch MA. J. Biol. Chem. 2002;277:10987. [PubMed] [Google Scholar] 10. Bonny C, Oberson A, Negri S, Sauser C, Schorderet DF. Diabetes. 2001;50:77. [PubMed] [Google Scholar] 11. Dickens M, Roger JS, Cavanagh J, Raitano A, Xia Z, Halpern JR, Greenberg Me personally, Sawyers CL, Davis RJ. Research. 1997;277:693. [PubMed] [Google Scholar] 12. Heo Y-S, Kim S-K, Seo CI, Kim Y-K, Sung B-J, Lee HS, Lee JI, Recreation area S-Y, Kim JH, Hwang KY, Hyun Y-L, Jeon YH, Ro S, Cho JM, Lee TG, Yang C-H. EMBO J. 2004;23:2185. [PMC free of charge content] [PubMed] [Google Scholar] 13. Kaneto H, Nakatani Y, Miyatsuka T, Kawamori D, Matsuoka T, Matsuhisa M, Kajimoto Y, Ichijo H, Yamasaki Y, Hori M. Nat. Med. 2004;10:1128. [PubMed] [Google Scholar] 14. Swahn B-M, Xue Y, Arzel E, Kallin E, Magnus A, Plobeck N, Viklund J. Bioorg. Med. Chem. Lett. 2006;16:1397. [PubMed] [Google Scholar] 15. Graczyk PP, Khan A, Bhatia GS, Palmer V, Medland D, Numata H, Oinuma H, Catchick J, Dunne A, Ellis M, Smales C, Whitfield J, Neame SJ, Shah B, Wilton D, Morgan L, Patel T, Chung R, Desmond H, Staddon JM, Sato N, Inoue A. Bioorg. Med. Chem. Lett. 2005;15:4666. [PubMed] [Google Scholar] 16. Gaillard P, Jeanclaude-Etter I, Ardissone V, Arkinstall S, Cambet Y, Camps M, Chabert C, Church D, Cirillo R, Gretener D, Halazy S, Nichols A, Szyndralewiez C, Vitte P-A, Gotteland J-P. J. Med. Chem. 2005;48:4596. [PubMed] [Google Scholar] 17. Szczepankiewicz BG, Kosogof C, Nelson LTJ, Liu G, Liu B, Zhao H, Serby MD, Xin Z, Liu M, Gum RJ, Haasch DL, Wang S, Clampit JE, Johnson EF, Lubben TH, Stashko MA, Olejniczak ET, Sun C, Dorwin SA, Haskins K, Abad-Zapatero C, Fry EH, Hutchins CW, Sham HL, Rondinone CM, Trevillyan JM. J. Med. Chem. 2006;49:3563. [PubMed] [Google Scholar] 18. Swahn B-M, Huerta F, Kallin E, Malmstr?m J, Weigelt T, Viklund J, Womack P, Xue Y, ?hberg L. Bioorg. Med. Chem. Lett. 2005;15:5095. [PubMed] [Google Scholar] 19. Rckle T, Biamonte M, Grippi-Vallotton T, Arkinstall S, Cambet Y, Camps M, Chabert C, Church DJ, Halazy S, Jiang X, Martinou I, Nichols A, Sauer W, Gotteland J-P. J. Med. Chem. 2004;47:6921. [PubMed] [Google Scholar] 20. Bennett BL, Sasaki DT, Murray BW, O’Leary EC, Sakata ST, Xu W, Leisten JC, Motiwala A, Pierce S, Satoh Y, Bhagwat SS, Manning AM, Anderson DW. Proc. Natl. Acad. Sci. 2001;98:13681. [PMC free article] [PubMed] [Google Scholar] 21. Teague SJ, Barber S, King S, Stein L. Tetrahedron Lett. 2005;46:4613. [Google Scholar] 22. Vazquez J, De SK, Chen L-H, Riel-Mehan M, Emdadi A, Cellitti J, Stebbins JL, Rega MF, Pellecchia M. J. Med. Chem. 2008;51:3460. [PMC free article] [PubMed] [Google Scholar] 23. Stebbins JL, De SK, Machleidt T, Becattini B, Vazquez J, Kuntzen C, Chen L-H, Cellitti JF, Riel-Mehan M, Emdadi A, Solinas G, Karin M, Pellecchia M. Proc. Natl. Acad. Sci. 2008;105:16809. [PMC free article] [PubMed] [Google Scholar] 24. Synthesis of 2-(5-nitrothiazol-2-ylthio)benzo[d]thiazole (87G3):.[PMC free article] [PubMed] [Google Scholar] 5. with this assay when assessment substrate competitive substances. Nonetheless, this selecting establishes that substance BI-87G3 can function within a mobile context. Open up in another window Amount 4 TR-FRET evaluation of c-Jun phosphorylation upon TNF-alpha arousal of HeLa cells in the current presence of increasing 87G3. To conclude, we successfully created a new group of JNK inhibitors, a lot of that are powerful in vitro. Our outcomes indicate that concentrating on the proteinCprotein connections between JNK and JIP with a little molecule is a fresh and appealing avenue for JNK related therapeutics. Acknowledgments We gratefully acknowledge economic support in the NIH (Grants or loans # DK073274 and “type”:”entrez-nucleotide”,”attrs”:”text”:”DK080263″,”term_id”:”187584901″DK080263) and Syndexa pharmaceuticals (to M.P.). Personal references and records 1. Manning G. Research. 2002;298:1912. [PubMed] [Google Scholar] 2. Manning AM, Davis RJ. Nat. Rev. Medication Breakthrough. 2003;2:554. [PubMed] [Google Scholar] 3. Bogoyevitch MA. Trends Mol. Med. 2005;11:232. [PubMed] [Google Scholar] 4. Gupta S, Barrett T, Whitmarsh AJ, Cavanagh J, Sluss HK, Drijard B, Davis RJ. EMBO J. 1996;15:2760. [PMC free article] [PubMed] [Google Scholar] 5. Kyriakis JM, Avruch J. Physiol. Rev. 2001;81:807. [PubMed] [Google Scholar] 6. Pearson G, Robinson R, Gibson TB, Xu BE, Karandikar M, Berman K, Cobb MH. Endocr. Rev. 2001;22:153. [PubMed] [Google Scholar] 7. Kallunki T, Deng T, Hibi M, Karin M. Cell. 1996;87:929. [PubMed] [Google Scholar] 8. Yang S-H, Whitmarsh AJ, Davis RJ, Sharrocks AD. EMBO J. 1998;17:1740. [PMC free article] [PubMed] [Google Scholar] 9. Barr RK, Kendrick TS, Bogoyevitch MA. J. Biol. Chem. 2002;277:10987. [PubMed] [Google Scholar] 10. Bonny C, Oberson A, Negri S, Sauser C, Schorderet DF. Diabetes. 2001;50:77. [PubMed] [Google Scholar] Diosmetin-7-O-beta-D-glucopyranoside 11. Dickens M, Roger JS, Cavanagh J, Raitano A, Xia Z, Halpern JR, Greenberg ME, Sawyers CL, Davis RJ. Science. 1997;277:693. [PubMed] [Google Scholar] 12. Heo Y-S, Kim S-K, Seo CI, Kim Y-K, Sung B-J, Lee HS, Lee JI, Park S-Y, Kim JH, Hwang KY, Hyun Y-L, Jeon YH, Ro S, Cho JM, Lee TG, Yang C-H. EMBO J. 2004;23:2185. [PMC free article] [PubMed] [Google Scholar] 13. Kaneto H, Nakatani Y, Miyatsuka T, Kawamori D, Matsuoka T, Matsuhisa M, Kajimoto Y, Ichijo H, Yamasaki Y, Hori M. Nat. Med. 2004;10:1128. [PubMed] [Google Scholar] 14. Swahn B-M, Xue Y, Arzel E, Kallin E, Magnus A, Plobeck N, Viklund J. Bioorg. Med. Chem. Lett. 2006;16:1397. [PubMed] [Google Scholar] 15. Graczyk PP, Khan A, Bhatia GS, Palmer V, Medland D, Numata H, Oinuma H, Catchick J, Dunne A, Ellis M, Smales C, Whitfield J, Neame SJ, Shah B, Wilton D, Morgan L, Patel T, Chung R, Desmond H, Staddon JM, Sato N, Inoue A. Bioorg. Med. Chem. Lett. 2005;15:4666. [PubMed] [Google Scholar] 16. Gaillard P, Jeanclaude-Etter I, Ardissone V, Arkinstall S, Cambet Y, Camps M, Chabert C, Church D, Cirillo R, Gretener D, Halazy S, Nichols A, Szyndralewiez C, Vitte P-A, Gotteland J-P. J. Med. Chem. 2005;48:4596. [PubMed] [Google Scholar] 17. Szczepankiewicz BG, Kosogof C, Nelson LTJ, Liu G, Liu B, Zhao H, Serby MD, Xin Z, Liu M, Gum RJ, Haasch DL, Wang S, Clampit JE, Johnson EF, Lubben TH, Stashko MA, Olejniczak ET, Sun C, Dorwin SA, Haskins K, Abad-Zapatero C, Fry EH, Hutchins CW, Sham HL, Rondinone CM, Trevillyan JM. J. Med. Chem. 2006;49:3563. [PubMed] [Google Scholar] 18. Swahn B-M, Huerta F, Kallin E, Malmstr?m J, Weigelt T, Viklund J, Womack P, Xue Y, ?hberg L. Bioorg. Med. Chem. Lett. 2005;15:5095. [PubMed] [Google Scholar] 19. Rckle T, Biamonte M, Grippi-Vallotton T, Arkinstall S, Cambet Y, Camps M, Chabert C, Church DJ, Halazy S, Jiang X, Martinou I, Nichols A, Sauer W, Gotteland J-P. J. Med. Chem. 2004;47:6921. [PubMed] [Google Scholar] 20. Bennett BL, Sasaki DT, Murray BW, O’Leary EC, Sakata ST, Xu W, Leisten JC, Motiwala A, Pierce S, Satoh Y, Bhagwat SS, Manning AM, Anderson DW. Proc. Natl. Acad. Sci. 2001;98:13681. [PMC free article] [PubMed] [Google Scholar] 21. Teague SJ, Barber S, King S, Stein L. Tetrahedron Lett. 2005;46:4613. [Google Scholar] 22. Vazquez J, De SK, Chen L-H, Riel-Mehan M, Emdadi A, Cellitti J, Stebbins JL, Rega MF, Pellecchia M. J. Med. Chem. 2008;51:3460. [PMC free article] [PubMed] [Google Scholar] 23. Stebbins JL, De SK, Machleidt T, Becattini B, Vazquez J, Kuntzen C, Chen L-H, Cellitti JF, Riel-Mehan M, Emdadi A, Solinas G, Karin M, Pellecchia M. Proc. Natl. Acad. Sci. 2008;105:16809. [PMC free article] [PubMed] [Google Scholar] 24. Synthesis of 2-(5-nitrothiazol-2-ylthio)benzo[d]thiazole (87G3): To a remedy of benzothiazol-2-thiol (167 mg, 1 mmol) in methanol (5 mL) was added MeONa (2.4 mL, 0.5 M solution in methanol, 1.2 mmol) at room temperature. After stirring for 5 min, 2-bromo-5-nitro thiazole (229 mg, Diosmetin-7-O-beta-D-glucopyranoside 1.1 mmol).Chem. conclusion, we successfully developed a brand new number of JNK inhibitors, a lot of that are potent in vitro. Our results indicate that targeting the proteinCprotein interaction between JNK and JIP using a small molecule is a brand new and promising avenue for JNK related therapeutics. Acknowledgments We gratefully acknowledge financial support in the NIH (Grants # DK073274 and “type”:”entrez-nucleotide”,”attrs”:”text”:”DK080263″,”term_id”:”187584901″DK080263) and Syndexa pharmaceuticals (to M.P.). References and notes 1. Manning G. Science. 2002;298:1912. [PubMed] [Google Scholar] 2. Manning AM, Davis RJ. Nat. Rev. Drug Discovery. 2003;2:554. [PubMed] [Google Scholar] 3. Bogoyevitch MA. Trends Mol. Med. 2005;11:232. [PubMed] [Google Scholar] 4. Gupta S, Barrett T, Whitmarsh AJ, Cavanagh J, Sluss HK, Drijard B, Davis RJ. EMBO J. 1996;15:2760. [PMC free article] [PubMed] [Google Scholar] 5. Kyriakis JM, Avruch J. Physiol. Rev. 2001;81:807. [PubMed] [Google Scholar] 6. Pearson G, Robinson R, Gibson TB, Xu BE, Karandikar M, Berman K, Cobb MH. Endocr. Rev. 2001;22:153. 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