| Title |
Design, synthesis, and biological evaluation of novel EF24 and EF31 analogs as potential IκB kinase β inhibitors for the treatment of pancreatic cancer
|
|---|---|
| Published in |
Drug Design, Development and Therapy, May 2017
|
| DOI | 10.2147/dddt.s133172 |
| Pubmed ID | |
| Authors |
Xuemeng Xie, Jinfu Tu, Heyi You, Bingren Hu |
| Abstract |
Given the important role that inhibitory kappa B (IκB) kinase β (IKKβ) plays in pancreatic cancer (PC) development and progression, inhibitors targeting IKKβ are believed to be increasingly popular as novel anti-PC therapies. Two synthetic molecules, named EF24 and EF31, exhibited favorable potential in terms of inhibition of both IKKβ activity and PC cell proliferation. Aiming to enhance their cellular efficacy and to analyze their structure-activity relationship, four series of EF24 and EF31 analogs were designed and synthesized. Through kinase activity and vitality screening of cancer cells, D6 displayed excellent inhibition of both IKKβ activity and PC cell proliferation. Additionally, multiple biological evaluations showed that D6 was directly bound to IKKβ and significantly suppressed the activation of the IKKβ/nuclear factor κB pathway induced by tumor necrosis factor-α, as well as effectively inducing cancer cell apoptosis. Moreover, molecular docking and molecular dynamics simulation analysis indicated that the dominant force between D6 and IKKβ comprised hydrophobic interactions. In conclusion, D6 may be a promising therapeutic agent for PC treatment and it also provides a structural lead for the design of novel IKKβ inhibitors. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 10 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 10 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 1 | 10% |
| Researcher | 1 | 10% |
| Lecturer | 1 | 10% |
| Student > Master | 1 | 10% |
| Unknown | 6 | 60% |
| Readers by discipline | Count | As % |
|---|---|---|
| Chemistry | 2 | 20% |
| Business, Management and Accounting | 1 | 10% |
| Energy | 1 | 10% |
| Medicine and Dentistry | 1 | 10% |
| Unknown | 5 | 50% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 March 2018.
All research outputs
#22,764,772
of 25,382,440 outputs
Outputs from Drug Design, Development and Therapy
#1,753
of 2,268 outputs
Outputs of similar age
#284,174
of 324,557 outputs
Outputs of similar age from Drug Design, Development and Therapy
#42
of 49 outputs
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