Discovery of Bisindole as a Novel Scaffold for Protein Tyrosine Phosphatase 1B Inhibitors
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim..
Protein tyrosine phosphatase 1B (PTP1B) has been proposed to be an effective target for the treatment of both type II diabetes and obesity. However, no PTP1B inhibitor has come into clinic application. Herein, we report mixed 3,3'-bisindoles as novel PTP1B inhibitors with low micromole-ranged inhibitory activity. The best active compound 9f inhibited PTP1B activity with an IC50 of 2.79 µM. Meanwhile, it had low cytotoxicity and enhanced glucose uptake in vitro. Further studies demonstrated that some of these active compounds had a specific selectivity over other PTPs. Computational analysis further showed the binding mode of compound 9f with the active pocket of PTP1B. Our studies provide a novel scaffold for further development of more promising PTP1B inhibitors and potential drugs for type II diabetes and obesity.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2017 |
|---|---|
| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:350 |
|---|---|
| Enthalten in: |
Archiv der Pharmazie - 350(2017), 1 vom: 01. Jan. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Jing, Changcheng [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 17.04.2017 Date Revised 17.04.2017 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1002/ardp.201600173 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM26752143X |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM26752143X | ||
| 003 | DE-627 | ||
| 005 | 20231224220849.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2017 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/ardp.201600173 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0891.xml |
| 035 | |a (DE-627)NLM26752143X | ||
| 035 | |a (NLM)28029177 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Jing, Changcheng |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Discovery of Bisindole as a Novel Scaffold for Protein Tyrosine Phosphatase 1B Inhibitors |
| 264 | 1 | |c 2017 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 17.04.2017 | ||
| 500 | |a Date Revised 17.04.2017 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. | ||
| 520 | |a Protein tyrosine phosphatase 1B (PTP1B) has been proposed to be an effective target for the treatment of both type II diabetes and obesity. However, no PTP1B inhibitor has come into clinic application. Herein, we report mixed 3,3'-bisindoles as novel PTP1B inhibitors with low micromole-ranged inhibitory activity. The best active compound 9f inhibited PTP1B activity with an IC50 of 2.79 µM. Meanwhile, it had low cytotoxicity and enhanced glucose uptake in vitro. Further studies demonstrated that some of these active compounds had a specific selectivity over other PTPs. Computational analysis further showed the binding mode of compound 9f with the active pocket of PTP1B. Our studies provide a novel scaffold for further development of more promising PTP1B inhibitors and potential drugs for type II diabetes and obesity | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Inhibitor | |
| 650 | 4 | |a Mixed 3,3′-bisindoles | |
| 650 | 4 | |a Molecular docking | |
| 650 | 4 | |a Protein tyrosine phosphatase 1B | |
| 650 | 7 | |a Enzyme Inhibitors |2 NLM | |
| 650 | 7 | |a Indoles |2 NLM | |
| 650 | 7 | |a Protein Tyrosine Phosphatase, Non-Receptor Type 1 |2 NLM | |
| 650 | 7 | |a EC 3.1.3.48 |2 NLM | |
| 650 | 7 | |a Glucose |2 NLM | |
| 650 | 7 | |a IY9XDZ35W2 |2 NLM | |
| 700 | 1 | |a Li, Ziyan |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, Kaili |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xiao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Beibei |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Wenhao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jia |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Tong |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, Suzhen |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Archiv der Pharmazie |d 1972 |g 350(2017), 1 vom: 01. Jan. |w (DE-627)NLM000013323 |x 1521-4184 |7 nnns |
| 773 | 1 | 8 | |g volume:350 |g year:2017 |g number:1 |g day:01 |g month:01 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1002/ardp.201600173 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 350 |j 2017 |e 1 |b 01 |c 01 | ||