التفاصيل البيبلوغرافية
| العنوان: |
First-in-Class Dual EZH2-HSP90 Inhibitor Eliciting Striking Antiglioblastoma Activity In Vitro and In Vivo |
| المؤلفون: |
Sachin Sharma, Shao-An Wang, Wen-Bin Yang, Hong-Yi Lin, Mei-Jung Lai, Hsien-Chung Chen, Tzu-Yuan Kao, Feng-Lin Hsu, Kunal Nepali, Tsung-I Hsu, Jing-Ping Liou |
| سنة النشر: |
2024 |
| مصطلحات موضوعية: |
Medicine, Cell Biology, Molecular Biology, Pharmacology, Immunology, Developmental Biology, Cancer, Hematology, Infectious Diseases, Virology, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, study results confirm, related gene expression, experimental mice xenografted, cenps protein expression, generation hsp90 inhibitors, magnificent dual ezh2, class dual ezh2, approved ezh2 inhibitor, resistant pt3r cells, 7 , resistant gbm cells, dual ezh2, pt3r cells, hsp90 inhibitor, dual inhibitor, resistant glioblastoma, vivo <, vitro < |
| الوصف: |
Structural analysis of tazemetostat, an FDA-approved EZH2 inhibitor, led us to pinpoint a suitable site for appendage with a pharmacophoric fragment of second-generation HSP90 inhibitors. Resultantly, a magnificent dual EZH2/HSP90 inhibitor was pinpointed that exerted striking cell growth inhibitory efficacy against TMZ-resistant Glioblastoma (GBM) cell lines. Exhaustive explorations of chemical probe 7 led to several revelations such as (i) compound 7 increased apoptosis/necrosis-related gene expression, whereas decreased M phase/kinetochore/spindle-related gene expression as well as CENPs protein expression in Pt3R cells; (ii) dual inhibitor 7 induced cell cycle arrest at the M phase; (iii) compound 7 suppressed reactive oxygen species (ROS) catabolism pathway, causing the death of TMZ-resistant GBM cells; and (iv) compound 7 elicited substantial in vivo anti-GBM efficacy in experimental mice xenografted with TMZ-resistant Pt3R cells. Collectively, the study results confirm the potential of dual EZH2-HSP90 inhibitor 7 as a tractable anti-GBM agent. |
| نوع الوثيقة: |
dataset |
| اللغة: |
unknown |
| Relation: |
https://figshare.com/articles/dataset/First-in-Class_Dual_EZH2-HSP90_Inhibitor_Eliciting_Striking_Antiglioblastoma_Activity_i_In_Vitro_i_and_i_In_Vivo_i_/25104061 |
| DOI: |
10.1021/acs.jmedchem.3c02053.s003 |
| الاتاحة: |
https://doi.org/10.1021/acs.jmedchem.3c02053.s003
https://figshare.com/articles/dataset/First-in-Class_Dual_EZH2-HSP90_Inhibitor_Eliciting_Striking_Antiglioblastoma_Activity_i_In_Vitro_i_and_i_In_Vivo_i_/25104061 |
| Rights: |
CC BY-NC 4.0 |
| رقم الانضمام: |
edsbas.BF9E5DA2 |
| قاعدة البيانات: |
BASE |