| 000 | 03507nlm1a2200553 4500 | ||
|---|---|---|---|
| 001 | 666255 | ||
| 005 | 20231030042031.0 | ||
| 035 | _a(RuTPU)RU\TPU\network\37459 | ||
| 035 | _aRU\TPU\network\36205 | ||
| 090 | _a666255 | ||
| 100 | _a20211213a2021 k y0engy50 ba | ||
| 101 | 0 | _aeng | |
| 102 | _aCH | ||
| 135 | _adrcn ---uucaa | ||
| 181 | 0 | _ai | |
| 182 | 0 | _ab | |
| 200 | 1 |
_aNovel c-Jun N-Terminal Kinase (JNK) Inhibitors with an 11H-Indeno[1,2-b]quinoxalin-11-one Scaffold _fS. A. Lyakhov, I. A. Shchepyotkin, A. S. Karpenko [et al.] |
|
| 203 |
_aText _celectronic |
||
| 300 | _aTitle screen | ||
| 320 | _a[References: 60 tit.] | ||
| 330 | _ac-Jun N-terminal kinase (JNK) plays a central role in stress signaling pathways implicated in important pathological processes, including rheumatoid arthritis and ischemia-reperfusion injury. Therefore, inhibition of JNK is of interest for molecular targeted therapy to treat various diseases. We synthesized 13 derivatives of our reported JNK inhibitor 11H-indeno[1,2-b]quinoxalin-11-one oxime and evaluated their binding to the three JNK isoforms and their biological effects. Eight compounds exhibited submicromolar binding affinity for at least one JNK isoform. Most of these compounds also inhibited lipopolysaccharide (LPS)-induced nuclear factor-kB/activating protein 1 (NF-kB/AP-1) activation and interleukin-6 (IL-6) production in human monocytic THP1-Blue cells and human MonoMac-6 cells, respectively. Selected compounds (4f and 4m) also inhibited LPS-induced c-Jun phosphorylation in MonoMac-6 cells, directly confirming JNK inhibition. We conclude that indenoquinoxaline-based oximes can serve as specific small-molecule modulators for mechanistic studies of JNKs, as well as potential leads for the development of anti-inflammatory drugs. | ||
| 461 | _tMolecules | ||
| 463 |
_tVol. 26, iss. 18 _v[5688, 18 p.] _d2021 |
||
| 610 | 1 | _aтруды учёных ТПУ | |
| 610 | 1 | _aэлектронный ресурс | |
| 610 | 1 | _ac-Jun N-terminal kinase | |
| 610 | 1 | _akinase inhibitor | |
| 610 | 1 | _a11H-indeno[1,2-b]quinoxalin-11-one | |
| 610 | 1 | _aoxime | |
| 610 | 1 | _ainterleukin-6 | |
| 610 | 1 | _anuclear factor-kB | |
| 610 | 1 | _aингибиторы | |
| 610 | 1 | _aкиназы | |
| 610 | 1 | _aтерапия | |
| 610 | 1 | _aпротивовоспалительные препараты | |
| 701 | 1 |
_aLyakhov _bS. A. _gSergey |
|
| 701 | 1 |
_aShchepyotkin _bI. A. _gIgor Aleksandrovich |
|
| 701 | 1 |
_aKarpenko _bA. S. _gAlexander |
|
| 701 | 1 |
_aDuma _bN. I. _gNanna |
|
| 701 | 1 |
_aGaidarzhy _bN. M. _gNadiya |
|
| 701 | 1 |
_aKirpotina _bL. N. _gLiliya Nikolaevna |
|
| 701 | 1 |
_aKovrizhina _bA. R. _cbiotechnology specialist _cResearch Engineer of Tomsk Polytechnic University _f1995- _gAnastasia Ruslanovna _2stltpush _3(RuTPU)RU\TPU\pers\46608 |
|
| 701 | 1 |
_aKhlebnikov _bA. I. _cChemist _cProfessor of Tomsk Polytechnic University _f1963- _gAndrey Ivanovich _2stltpush _3(RuTPU)RU\TPU\pers\33927 |
|
| 701 | 1 |
_aBagryanskaya _bI. Yu. _gIrina Yurjevna |
|
| 701 | 1 |
_aQuinn _bM. T. _gMark |
|
| 712 | 0 | 2 |
_aНациональный исследовательский Томский политехнический университет _bИнженерная школа новых производственных технологий _bНаучно-образовательный центр Н. М. Кижнера _h7872 _2stltpush _3(RuTPU)RU\TPU\col\23556 |
| 801 | 2 |
_aRU _b63413507 _c20211213 _gRCR |
|
| 856 | 4 | 0 | _uhttps://doi.org/10.3390/molecules26185688 |
| 942 | _cCF | ||