In silico identification of novel kinase inhibitors by targeting B-Rafv660e from natural products database
| LEADER | caa a22 4500 | ||
|---|---|---|---|
| 001 | 605512442 | ||
| 003 | CHVBK | ||
| 005 | 20210128100655.0 | ||
| 007 | cr unu---uuuuu | ||
| 008 | 210128e20150401xx s 000 0 eng | ||
| 024 | 7 | 0 | |a 10.1007/s00894-015-2647-8 |2 doi |
| 035 | |a (NATIONALLICENCE)springer-10.1007/s00894-015-2647-8 | ||
| 245 | 0 | 0 | |a In silico identification of novel kinase inhibitors by targeting B-Rafv660e from natural products database |h [Elektronische Daten] |c [Zi-jie Wang, Zhi-ning Wan, Xu-dong Chen, Chuan-fang Wu, Guo-long Gao, Rong Liu, Zheng Shi, Jin-ku Bao] |
| 520 | 3 | |a The Ras/Raf/MEK/ERK (MAPK) signaling pathway has gained much attention from scientific community for therapeutic intervention in the past decades, specifically in oncology. Notably, a most prevalent B-Rafv600e mutant in Raf kinase family exhibits elevated kinase activity and results in constitutive activation of the MAPK pathway, thus making it a promising drug target for cancer therapy. Herein, virtual screening is applied to identify its potential inhibitors. Following the 25 ns molecular dynamic (MD) simulations, ZINC38541768, ZINC38541767, and ZINC12496469 are identified as B-Rafv600e potential inhibitors in a DFG-in conformation. Furthermore, according to the molecular mechanics/generalized born surface area (MM/GBSA) method, these three small molecules exhibit similar and good binding affinity toward B-Rafv600e (−38.76kcalmol−1, −42.60kcalmol−1, and −39.04kcalmol−1). At the same time, several critical residues, such as I463, V471 in the P-loop, and DFG motif residue D594 within the A-loop, are also well clarified. All these results may not only indicate some future applications of inhibitors targeting B-Rafv600e, but also benefit B-Rafv600e harboring cancer patients. Graphical Abstract Novel kinase inhibitors by targeting B-Rafv660e ᅟ | |
| 540 | |a Springer-Verlag Berlin Heidelberg, 2015 | ||
| 690 | 7 | |a B-Rafv600e |2 nationallicence | |
| 690 | 7 | |a Kinase inhibitors |2 nationallicence | |
| 690 | 7 | |a MD simulation |2 nationallicence | |
| 690 | 7 | |a MM/GBSA |2 nationallicence | |
| 690 | 7 | |a Virtual screening |2 nationallicence | |
| 700 | 1 | |a Wang |D Zi-jie |u School of Life Sciences and Key Laboratory of Bio-resources, Ministry of Education, & State Key Laboratory of Biotherapy, Sichuan University, 610064, Chengdu, China |4 aut | |
| 700 | 1 | |a Wan |D Zhi-ning |u School of Life Sciences and Key Laboratory of Bio-resources, Ministry of Education, & State Key Laboratory of Biotherapy, Sichuan University, 610064, Chengdu, China |4 aut | |
| 700 | 1 | |a Chen |D Xu-dong |u School of Life Sciences and Key Laboratory of Bio-resources, Ministry of Education, & State Key Laboratory of Biotherapy, Sichuan University, 610064, Chengdu, China |4 aut | |
| 700 | 1 | |a Wu |D Chuan-fang |u School of Life Sciences and Key Laboratory of Bio-resources, Ministry of Education, & State Key Laboratory of Biotherapy, Sichuan University, 610064, Chengdu, China |4 aut | |
| 700 | 1 | |a Gao |D Guo-long |u Sichuan International Travel Healthcare Centre, 610041, Chengdu, China |4 aut | |
| 700 | 1 | |a Liu |D Rong |u Medical and Nursing School, Chengdu University, 610015, Chengdou, China |4 aut | |
| 700 | 1 | |a Shi |D Zheng |u Medical and Nursing School, Chengdu University, 610015, Chengdou, China |4 aut | |
| 700 | 1 | |a Bao |D Jin-ku |u School of Life Sciences and Key Laboratory of Bio-resources, Ministry of Education, & State Key Laboratory of Biotherapy, Sichuan University, 610064, Chengdu, China |4 aut | |
| 773 | 0 | |t Journal of Molecular Modeling |d Springer Berlin Heidelberg |g 21/4(2015-04-01), 1-9 |x 1610-2940 |q 21:4<1 |1 2015 |2 21 |o 894 | |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s00894-015-2647-8 |q text/html |z Onlinezugriff via DOI |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 900 | 7 | |a Metadata rights reserved |b Springer special CC-BY-NC licence |2 nationallicence | |
| 908 | |D 1 |a research-article |2 jats | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-springer | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1007/s00894-015-2647-8 |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Wang |D Zi-jie |u School of Life Sciences and Key Laboratory of Bio-resources, Ministry of Education, & State Key Laboratory of Biotherapy, Sichuan University, 610064, Chengdu, China |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Wan |D Zhi-ning |u School of Life Sciences and Key Laboratory of Bio-resources, Ministry of Education, & State Key Laboratory of Biotherapy, Sichuan University, 610064, Chengdu, China |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Chen |D Xu-dong |u School of Life Sciences and Key Laboratory of Bio-resources, Ministry of Education, & State Key Laboratory of Biotherapy, Sichuan University, 610064, Chengdu, China |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Wu |D Chuan-fang |u School of Life Sciences and Key Laboratory of Bio-resources, Ministry of Education, & State Key Laboratory of Biotherapy, Sichuan University, 610064, Chengdu, China |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Gao |D Guo-long |u Sichuan International Travel Healthcare Centre, 610041, Chengdu, China |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Liu |D Rong |u Medical and Nursing School, Chengdu University, 610015, Chengdou, China |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Shi |D Zheng |u Medical and Nursing School, Chengdu University, 610015, Chengdou, China |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Bao |D Jin-ku |u School of Life Sciences and Key Laboratory of Bio-resources, Ministry of Education, & State Key Laboratory of Biotherapy, Sichuan University, 610064, Chengdu, China |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t Journal of Molecular Modeling |d Springer Berlin Heidelberg |g 21/4(2015-04-01), 1-9 |x 1610-2940 |q 21:4<1 |1 2015 |2 21 |o 894 | ||