التفاصيل البيبلوغرافية
| العنوان: |
Discovery of a Dual Tubulin and Poly(ADP-Ribose) Polymerase‑1 Inhibitor by Structure-Based Pharmacophore Modeling, Virtual Screening, Molecular Docking, and Biological Evaluation |
| المؤلفون: |
Lufeng Zheng (4668964), Ren Ren (59774), Xiaolian Sun (1306611), Yunting Zou (11590656), Yiru Shi (11407281), Bin Di (2070112), Miao-Miao Niu (11590659) |
| سنة النشر: |
2021 |
| المجموعة: |
Smithsonian Institution: Digital Repository |
| مصطلحات موضوعية: |
Biophysics, Biochemistry, Cell Biology, Genetics, Molecular Biology, Pharmacology, Biotechnology, Cancer, Hematology, Computational Biology, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, vivo assessment indicates, notable side effects, cellular assays reveal, cell cycle arrest, based pharmacophore modeling, 231 xenograft tumors, toxic antitumor agent, human cancer cells, based virtual screening, poly ( adp, virtual screening, cancer therapy, antitumor role, tube formation, studies indicate, strand breaks, nude mouse, multiple mechanisms |
| الوصف: |
Dual inhibition of tubulin and poly(ADP-ribose) polymerase-1 (PARP-1) may become an attractive approach for cancer therapy. Here, we discover a dual tubulin/PARP-1 inhibitor (termed as TP-3) using structure-based virtual screening. TP-3 shows strong dual inhibitory effects on both tubulin and PARP-1. Cellular assays reveal that TP-3 shows superior antiproliferative activities against human cancer cells, including breast, liver, ovarian, and cervical cancers. Further studies indicate that TP-3 plays an antitumor role through multiple mechanisms, including the disturbance of the microtubule network and the PARP-1 DNA repairing function, accumulation of DNA double-strand breaks, inhibition of the tube formation, and induction of G2/M cell cycle arrest and apoptosis. In vivo assessment indicates that TP-3 inhibits the growth of MDA-MB-231 xenograft tumors in nude mouse with no notable side effects. These data demonstrate that TP-3 is a dual-targeting, high-efficacy, and low-toxic antitumor agent. |
| نوع الوثيقة: |
dataset |
| اللغة: |
unknown |
| Relation: |
https://figshare.com/articles/dataset/Discovery_of_a_Dual_Tubulin_and_Poly_ADP-Ribose_Polymerase_1_Inhibitor_by_Structure-Based_Pharmacophore_Modeling_Virtual_Screening_Molecular_Docking_and_Biological_Evaluation/16843305 |
| DOI: |
10.1021/acs.jmedchem.1c00932.s009 |
| الاتاحة: |
https://doi.org/10.1021/acs.jmedchem.1c00932.s009 |
| Rights: |
CC BY-NC 4.0 |
| رقم الانضمام: |
edsbas.B68A76E9 |
| قاعدة البيانات: |
BASE |