Item request has been placed!
×
Item request cannot be made.
×
![loading](/sites/all/modules/hf_eds/images/loading.gif)
Processing Request
Inhibition of the MDM2 E3 Ligase induces apoptosis and autophagy in wild-type and mutant p53 models of multiple myeloma, and acts synergistically with ABT-737.
Item request has been placed!
×
Item request cannot be made.
×
![loading](/sites/all/modules/hf_eds/images/loading.gif)
Processing Request
- معلومة اضافية
- المصدر:
Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
- بيانات النشر:
Original Publication: San Francisco, CA : Public Library of Science
- الموضوع:
- نبذة مختصرة :
Intracellular proteolytic pathways have been validated as rational targets in multiple myeloma with the approval of two proteasome inhibitors in this disease, and with the finding that immunomodulatory agents work through an E3 ubiquitin ligase containing Cereblon. Another E3 ligase that could be a rational target is the murine double minute (MDM) 2 protein, which plays a role in p53 turnover. A novel inhibitor of this complex, MI-63, was found to induce apoptosis in p53 wild-type myeloma models in association with activation of a p53-mediated cell death program. MI-63 overcame adhesion-mediated drug resistance, showed anti-tumor activity in vivo, enhanced the activity of bortezomib and lenalidomide, and also overcame lenalidomide resistance. In mutant p53 models, inhibition of MDM2 with MI-63 also activated apoptosis, albeit at higher concentrations, and this was associated with activation of autophagy. When MI-63 was combined with the BH3 mimetic ABT-737, enhanced activity was seen in both wild-type and mutant p53 models. Finally, this regimen showed efficacy against primary plasma cells from patients with newly diagnosed and relapsed/refractory myeloma. These findings support the translation of novel MDM2 inhibitors both alone, and in combination with other novel agents, to the clinic for patients with multiple myeloma.
- References:
Blood. 2011 Oct 13;118(15):4140-9. (PMID: 21844567)
J Biol Chem. 2010 Apr 2;285(14):10850-61. (PMID: 20123989)
Blood. 2012 Aug 2;120(5):947-59. (PMID: 22645181)
J Med Chem. 2006 Jun 15;49(12):3432-5. (PMID: 16759082)
Br J Haematol. 2014 Mar;164(6):811-21. (PMID: 24328678)
Blood. 1997 Sep 1;90(5):1982-92. (PMID: 9292533)
EMBO Rep. 2007 Jan;8(1):84-90. (PMID: 17170761)
Lancet Oncol. 2012 Nov;13(11):1133-40. (PMID: 23084521)
Haematologica. 2009 Feb;94(2):270-5. (PMID: 19144659)
Blood. 2008 Mar 1;111(5):2516-20. (PMID: 17975015)
Clin Cancer Res. 2009 Dec 1;15(23):7153-60. (PMID: 19934289)
J Clin Oncol. 2012 Feb 1;30(4):445-52. (PMID: 22215754)
J Pharmacol Exp Ther. 2013 Sep;346(3):381-92. (PMID: 23820125)
Blood. 2008 Nov 15;112(10):4235-46. (PMID: 18337559)
Blood. 2006 Jan 1;107(1):257-64. (PMID: 16166592)
Autophagy. 2007 Jan-Feb;3(1):72-4. (PMID: 17102582)
Cancer Res. 2012 Sep 1;72(17):4562-73. (PMID: 22738917)
Science. 2004 Feb 6;303(5659):844-8. (PMID: 14704432)
Leukemia. 2003 Oct;17(10):2036-45. (PMID: 14513055)
Blood. 2007 Apr 15;109(8):3489-95. (PMID: 17209057)
Clin Cancer Res. 2008 Mar 15;14(6):1649-57. (PMID: 18347166)
Cancer Res. 2001 Apr 1;61(7):3071-6. (PMID: 11306489)
Mol Cancer Ther. 2012 Oct;11(10):2243-53. (PMID: 22933706)
Cancer Cell. 2010 Oct 19;18(4):367-81. (PMID: 20951946)
Blood. 1998 Aug 1;92(3):802-9. (PMID: 9680348)
Leukemia. 2012 Nov;26(11):2326-35. (PMID: 22552008)
J Clin Oncol. 2012 Sep 1;30(25):3127-35. (PMID: 22649144)
Blood. 2010 Oct 14;116(15):e56-65. (PMID: 20616218)
Cancer Res. 2009 Sep 15;69(18):7347-56. (PMID: 19738071)
Nat Rev Clin Oncol. 2011 Apr 26;8(8):479-91. (PMID: 21522124)
Ann Hematol. 2003 Jul;82(7):405-9. (PMID: 12783209)
Blood. 2011 Nov 3;118(18):4771-9. (PMID: 21860026)
Mol Cancer Ther. 2007 Mar;6(3):1062-9. (PMID: 17363499)
Biochem Biophys Res Commun. 2012 Mar 30;420(1):48-53. (PMID: 22402281)
Expert Opin Ther Pat. 2013 Apr;23(4):425-48. (PMID: 23374098)
Genes Dev. 1994 May 15;8(10):1235-46. (PMID: 7926727)
Oncogene. 1994 Sep;9(9):2523-9. (PMID: 8058315)
J Biol Chem. 2011 Apr 1;286(13):11009-20. (PMID: 21189262)
Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3933-8. (PMID: 18316739)
Br J Haematol. 1994 Oct;88(2):415-8. (PMID: 7803295)
Haematologica. 2003 May;88(5):529-37. (PMID: 12745272)
Nat Cell Biol. 2008 Jun;10(6):676-87. (PMID: 18454141)
Cancer Biol Ther. 2010 Jun 1;9(11):936-44. (PMID: 20418664)
Blood. 2012 Oct 18;120(16):3260-70. (PMID: 22932796)
Leukemia. 2014 May;28(5):1122-8. (PMID: 24157580)
Blood Rev. 2010 Nov;24 Suppl 1:S5-11. (PMID: 21126636)
Oncogene. 2011 Mar 17;30(11):1329-40. (PMID: 21057542)
Leukemia. 2009 Nov;23(11):1964-79. (PMID: 19741722)
J Clin Oncol. 2010 Mar 1;28(7):1209-14. (PMID: 20085933)
N Engl J Med. 2013 Feb 14;368(7):651-62. (PMID: 23406030)
Leukemia. 2013 Jan;27(1):226-32. (PMID: 22705990)
Nat Rev Cancer. 2012 Apr 26;12(6):401-10. (PMID: 22534666)
Leukemia. 2014 Feb;28(2):373-83. (PMID: 23760401)
Leuk Res. 2011 Jan;35(1):95-8. (PMID: 20537706)
J Am Chem Soc. 2011 Feb 9;133(5):1244-7. (PMID: 21210687)
Science. 2014 Jan 17;343(6168):305-9. (PMID: 24292623)
Cell. 2006 Jul 14;126(1):121-34. (PMID: 16839881)
Leukemia. 2014 May;28(5):1129-31. (PMID: 24166296)
Cancer Res. 2005 Jun 1;65(11):4673-82. (PMID: 15930285)
FEBS Lett. 1999 Mar 19;447(1):5-9. (PMID: 10218570)
Blood. 2005 Nov 15;106(10):3609-17. (PMID: 16081689)
Oncogene. 2014 Aug 28;33(35):4365-76. (PMID: 24096477)
Blood. 2003 Feb 15;101(4):1530-4. (PMID: 12393500)
CA Cancer J Clin. 2013 Jan;63(1):11-30. (PMID: 23335087)
- Grant Information:
P30 CA016672 United States CA NCI NIH HHS; P50 CA142509 United States CA NCI NIH HHS
- الرقم المعرف:
0 (ABT-737)
0 (Biphenyl Compounds)
0 (Indoles)
0 (MI-63 compound)
0 (Nitrophenols)
0 (Piperazines)
0 (Spiro Compounds)
0 (Sulfonamides)
0 (Tumor Suppressor Protein p53)
EC 2.3.2.27 (MDM2 protein, human)
EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
- الموضوع:
Date Created: 20140903 Date Completed: 20150518 Latest Revision: 20211021
- الموضوع:
20221213
- الرقم المعرف:
PMC4151993
- الرقم المعرف:
10.1371/journal.pone.0103015
- الرقم المعرف:
25181509
No Comments.