Identification of a novel selective inhibitor of mutant isocitrate dehydrogenase 1 at allosteric site by docking-based virtual screening
Isocitrate dehydrogenase 1 (IDH1), catalyzing oxidative decarboxylation of isocitrate to provide energy for aerobic organisms, is an essential enzyme in the tricarboxylic acid cycle. However, mutant IDH1 (mIDH1) produces oncometabolite D-2-hydroxyglutarate (D2HG) and has recently been confirmed in s...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
26 Sep 2016
|
| In: |
RSC Advances
Year: 2016, Volume: 6, Issue: 99, Pages: 96735-96742 |
| ISSN: | 2046-2069 |
| DOI: | 10.1039/C6RA21617J |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1039/C6RA21617J Verlag, Volltext: https://pubs.rsc.org/en/content/articlelanding/2016/ra/c6ra21617j 
|
| Author Notes: | Fangxia Zou, Stefan Pusch, Jessica Eisel, Tianfang Ma, Qihua Zhu, Dawei Deng, Yueqing Gu, Yungen Xu, Andreas von Deimling and Xiaoming Zha |
MARC
| LEADER | 00000caa a22000002c 4500 | ||
|---|---|---|---|
| 001 | 1580369200 | ||
| 003 | DE-627 | ||
| 005 | 20220814232128.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 180824s2016 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1039/C6RA21617J |2 doi | |
| 035 | |a (DE-627)1580369200 | ||
| 035 | |a (DE-576)510369200 | ||
| 035 | |a (DE-599)BSZ510369200 | ||
| 035 | |a (OCoLC)1341017529 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Zou, Fangxia |e VerfasserIn |0 (DE-588)1165340984 |0 (DE-627)1029424330 |0 (DE-576)510370195 |4 aut | |
| 245 | 1 | 0 | |a Identification of a novel selective inhibitor of mutant isocitrate dehydrogenase 1 at allosteric site by docking-based virtual screening |c Fangxia Zou, Stefan Pusch, Jessica Eisel, Tianfang Ma, Qihua Zhu, Dawei Deng, Yueqing Gu, Yungen Xu, Andreas von Deimling and Xiaoming Zha |
| 246 | 3 | 0 | |a one |
| 264 | 1 | |c 26 Sep 2016 | |
| 300 | |a 8 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 10.12.2019 | ||
| 520 | |a Isocitrate dehydrogenase 1 (IDH1), catalyzing oxidative decarboxylation of isocitrate to provide energy for aerobic organisms, is an essential enzyme in the tricarboxylic acid cycle. However, mutant IDH1 (mIDH1) produces oncometabolite D-2-hydroxyglutarate (D2HG) and has recently been confirmed in several types of cancers, particularly in glioma and acute myeloid leukemia. Herein a docking-based virtual screening (VS) of SPECS library was conducted for the allosteric site of mIDH1. The cellular evaluation of the hit compounds led to the identification of FX-03 as a novel selective mIDH1 inhibitor at allosteric site with IC50 values of 55.50 μM and 68.38 μM in HEK-293T cells transfected with IDH1 R132H and IDH1 R132C, respectively. Importantly, FX-03 owned significant selectivity with no inhibition in HEK-293T cells transfected with IDH1 WT. These findings indicate that VS of mIDH1's allosteric site represents a useful strategy for discovery of selective mIDH1 inhibitors and FX-03 deserves further optimization as a lead compound in future study. | ||
| 700 | 1 | |a Pusch, Stefan |d 1979- |e VerfasserIn |0 (DE-588)137014155 |0 (DE-627)58945224X |0 (DE-576)30150623X |4 aut | |
| 700 | 1 | |a Deimling, Andreas von |d 1959- |e VerfasserIn |0 (DE-588)103034115X |0 (DE-627)735093946 |0 (DE-576)378138065 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |a Royal Society of Chemistry |t RSC Advances |d London : RSC Publishing, 2011 |g 6(2016), 99, Seite 96735-96742 |h Online-Ressource |w (DE-627)666217866 |w (DE-600)2623224-8 |w (DE-576)349040303 |x 2046-2069 |7 nnas |
| 773 | 1 | 8 | |g volume:6 |g year:2016 |g number:99 |g pages:96735-96742 |g extent:8 |a Identification of a novel selective inhibitor of mutant isocitrate dehydrogenase 1 at allosteric site by docking-based virtual screening |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1039/C6RA21617J |x Verlag |x Resolving-System |3 Volltext |
| 856 | 4 | 0 | |u https://pubs.rsc.org/en/content/articlelanding/2016/ra/c6ra21617j |x Verlag |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20180824 | ||
| 993 | |a Article | ||
| 994 | |a 2016 | ||
| 998 | |g 103034115X |a Deimling, Andreas von |m 103034115X:Deimling, Andreas von |d 910000 |d 912000 |e 910000PD103034115X |e 912000PD103034115X |k 0/910000/ |k 1/910000/912000/ |p 9 | ||
| 998 | |g 137014155 |a Pusch, Stefan |m 137014155:Pusch, Stefan |d 910000 |d 912000 |e 910000PP137014155 |e 912000PP137014155 |k 0/910000/ |k 1/910000/912000/ |p 2 | ||
| 999 | |a KXP-PPN1580369200 |e 3023083401 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"person":[{"given":"Fangxia","role":"aut","display":"Zou, Fangxia","family":"Zou"},{"given":"Stefan","role":"aut","family":"Pusch","display":"Pusch, Stefan"},{"given":"Andreas von","role":"aut","family":"Deimling","display":"Deimling, Andreas von"}],"type":{"bibl":"article-journal","media":"Online-Ressource"},"relHost":[{"type":{"bibl":"periodical","media":"Online-Ressource"},"recId":"666217866","disp":"Royal Society of ChemistryRSC Advances","part":{"volume":"6","pages":"96735-96742","text":"6(2016), 99, Seite 96735-96742","issue":"99","extent":"8","year":"2016"},"pubHistory":["1.2011 -"],"corporate":[{"role":"aut","display":"Royal Society of Chemistry"}],"origin":[{"dateIssuedKey":"2011","publisherPlace":"London","dateIssuedDisp":"2011-","publisher":"RSC Publishing"}],"id":{"issn":["2046-2069"],"zdb":["2623224-8"],"eki":["666217866"]},"physDesc":[{"extent":"Online-Ressource"}],"title":[{"title_sort":"RSC Advances","subtitle":"an international journal to further the chemical sciences","title":"RSC Advances"}],"language":["eng"],"note":["Gesehen am 20.03.2017"],"name":{"displayForm":["Royal Society of Chemistry"]}}],"origin":[{"dateIssuedDisp":"26 Sep 2016","dateIssuedKey":"2016"}],"id":{"doi":["10.1039/C6RA21617J"],"eki":["1580369200"]},"recId":"1580369200","title":[{"title":"Identification of a novel selective inhibitor of mutant isocitrate dehydrogenase 1 at allosteric site by docking-based virtual screening","title_sort":"Identification of a novel selective inhibitor of mutant isocitrate dehydrogenase 1 at allosteric site by docking-based virtual screening"}],"physDesc":[{"extent":"8 S."}],"language":["eng"],"note":["Gesehen am 10.12.2019"],"name":{"displayForm":["Fangxia Zou, Stefan Pusch, Jessica Eisel, Tianfang Ma, Qihua Zhu, Dawei Deng, Yueqing Gu, Yungen Xu, Andreas von Deimling and Xiaoming Zha"]}} | ||
| SRT | |a ZOUFANGXIAIDENTIFICA2620 | ||