Bardoxolone

Orukọ Kemikali:

(4aS,6aR,6bS,8aR,12aS,14aR,14bS)-11-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-diox o-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,12a,14,14a,14b-octadecahydropicene-4a-carboxylic acid

KỌỌDỌ SMILES:

CC (C)([C @](CC[C@@]([C@@]1(CC[C@]2(CCC @]2(CCC(C)(C[C@]2([C @] 13[H) ])[H])C)C(O)=O)C)4C)5[H])C(C(C#N)=C[C@]5(C)C4=CC3=O)=O

Koodu InChi:

InChi=1S/C31H41NO4/c1-26(2)10-12-31(25(35)36)13-11-30(7)23(19(31)16-26)20(33)14-22- 28 (5) 15-18 (17-32) 24 (34). )27 (3,4)21 (28)8-9-29(22,30)6/h14-15,19,21,23H,8-13,16H2,1-7H3,(H,35,36) /t19-,21-,23-,28-,29+,30+,31-/m0/s1

Bọtini InChi:

TXGZJQLMVSIZEI-UQMAOPSPSA-N

Koko-ọrọ:

Bardoxolone, RTA 402, CCDO, RTA-402, RTA402, 218600-44-3

Solubility:Tiotuka ni DMSO

Ibi ipamọ:0 - 4°C fun igba kukuru (ọjọ si awọn ọsẹ), tabi -20°C fun igba pipẹ (osu).

Apejuwe:

Awọn apakan kidinrin lati awọn obo ti a ṣe itọju methyl Bardoxolone ṣe afihan ikosile amuaradagba megalin ti dinku laibikita ikosile mRNA ti o jọra kọja awọn ẹgbẹ. Idinku wiwo ninu ikosile amuaradagba megalin jẹ timo nipasẹ awọn itupalẹ densitometry, eyiti o ṣe afihan pe iṣakoso Bardoxolone methyl ni pataki dinku ikosile amuaradagba megalin ninu kidinrin ọbọ. Isakoso methyl Bardoxolone ko ni ipa lori ikosile amuaradagba ti cubilin ninu kidinrin tabi ikosile mRNA ti cubilin ninu kidinrin. Iyọkuro creatinine ninu awọn obo ti a nṣakoso Bardoxolone methyl ni pataki yatọ si iyẹn ni ipilẹṣẹ ati ni awọn ẹranko ti a tọju ọkọ ni ọjọ 28. Lẹhin awọn ọjọ 28 ti iṣakoso Bardoxolone methyl, ito albumin-to-creatinine ratios (UACRs), ti a pinnu lati ito wakati 24 collections, ti wa ni significantly pọ akawe pẹlu awon ti o wa ni eranko gbigba ọkọ. Ninu akọsilẹ, UACRs dinku 53.3% ninu awọn ẹranko ti a ṣe itọju ọkọ ati pe o pọ si 27.9% ni awọn obo ti a ṣe itọju Bardoxolone methyl[3]. Awọn eku C57BL/6J ọkunrin ni a nṣakoso BARD ẹnu lakoko ifunni HFD (HFD/BARD), jẹ ounjẹ ti o sanra ga (HFD), tabi jẹ ounjẹ ọra kekere (LFD) fun ọsẹ 21. Ti a ṣe afiwe pẹlu awọn eku LFD, awọn eku HFD ni alekun ti o samisi ni nọmba awọn ẹya F4/80 ade-bii (+ 95%; p<0.001), eyiti BARD ni idiwọ imunadoko (-50%; p<0.01). Bakanna, nọmba awọn macrophages interstitial F4/80 ga ni pataki ninu awọn eku HFD nipasẹ 98% (p<0.001) ni akawe pẹlu awọn eku LFD ati nipasẹ 32% (p<0.01) ni akawe pẹlu awọn eku HFD/BARD[4].

Àfojúsùn: Nrf-2