Item request has been placed!
×
Item request cannot be made.
×
![loading](/sites/all/modules/hf_eds/images/loading.gif)
Processing Request
Entinostat-Bortezomib Hybrids against Multiple Myeloma.
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: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE
- بيانات النشر:
Original Publication: Basel, Switzerland : MDPI, c1995-
- الموضوع:
- نبذة مختصرة :
Although proteasome inhibitors have emerged as the therapeutic backbone of multiple myeloma treatment, patients often relapse and become drug refractory. The combination between proteasome and histone deacetylase inhibitors has shown to be more efficient compared to monotherapy by enhancing the anti-myeloma activity and improving the patient's lifetime expectancy. Hybrid molecules, combining two drugs/pharmacophores in a single molecular entity, offer improved effectiveness by modulating more than one target and circumventing differences in the pharmacokinetic and pharmacodynamic profiles, which are the main disadvantages of combination therapy. Therefore, eleven histone deacetylase-proteasome inhibitor hybrids were synthesized, combining pharmacophores of entinostat and bortezomib. Compound 3 displayed the strongest antiproliferative activity with an IC 50 value of 9.5 nM in the multiple myeloma cells RPMI 8226, 157.7 nM in the same cell line resistant to bortezomib, and 13.1 nM in a 3D spheroid model containing multiple myeloma and mesenchymal stem cells. Moreover, the compound inhibited 33% of histone deacetylase activity when RPMI 8226 cells were treated for 8 h at 10 µM. It also inhibited the proteasome activity with an IC 50 value of 23.6 nM.
- References:
Eur J Med Chem. 2020 Jun 1;195:112270. (PMID: 32302879)
J Med Chem. 2020 May 14;63(9):4701-4715. (PMID: 32267687)
Chemistry. 2018 Feb 16;24(10):2360-2364. (PMID: 29314448)
J Vis Exp. 2017 Aug 10;(126):. (PMID: 28829415)
Clin Pharmacol. 2016 May 06;8:35-44. (PMID: 27226735)
Am J Hematol. 2022 Aug;97(8):1086-1107. (PMID: 35560063)
Methods Enzymol. 2005;398:364-78. (PMID: 16275343)
Asia Pac J Clin Oncol. 2021 Feb;17(1):29-35. (PMID: 32920949)
Leukemia. 2020 Jan;34(1):196-209. (PMID: 31142847)
Org Biomol Chem. 2013 Aug 7;11(29):4757-63. (PMID: 23784627)
Leukemia. 2014 Mar;28(3):680-9. (PMID: 23913134)
J Med Chem. 2018 Nov 21;61(22):10299-10309. (PMID: 30365892)
Cancers (Basel). 2021 Mar 11;13(6):. (PMID: 33799793)
Cancer Lett. 2009 Aug 8;280(2):168-76. (PMID: 19103471)
Biol Chem. 2012 Oct;393(10):1101-20. (PMID: 23091276)
Blood. 2022 May 12;139(19):2904-2917. (PMID: 35007326)
JAMA. 2022 Feb 01;327(5):464-477. (PMID: 35103762)
Cancer Lett. 2010 Oct 28;296(2):233-40. (PMID: 20447761)
- Contributed Indexing:
Keywords: HDAC inhibitors; drug resistance; hybrid inhibitors; multiple myeloma; proteasome inhibitors
- الرقم المعرف:
69G8BD63PP (Bortezomib)
0 (Antineoplastic Agents)
1ZNY4FKK9H (entinostat)
EC 3.4.25.1 (Proteasome Endopeptidase Complex)
0 (Boronic Acids)
0 (Proteasome Inhibitors)
0 (Histone Deacetylase Inhibitors)
EC 3.5.1.98 (Histone Deacetylases)
- الموضوع:
Date Created: 20230211 Date Completed: 20230214 Latest Revision: 20230214
- الموضوع:
20240628
- الرقم المعرف:
PMC9920246
- الرقم المعرف:
10.3390/molecules28031456
- الرقم المعرف:
36771118
No Comments.