SR9011 CAS 1379686-29-9 UBUSHAKASHATSI

SR9011ni REV-ERBα/βAgoniste, abagize umuryango wa reseptor nucleaire, basanze bagenga metabolisme yimitsi yibinyabuzima.Huang Guodong yasanze SR9011 igira uruhare runini mugutunganya injyana ya zebrafish autophagy gene.

Intungamubiri za SR9011 ntizifite ligand ihuza ligand kuri C-terminal, ariko irashobora kubuza imvugo ya poroteyine ya Rev erb mugushakisha reseptor inhibitor na histone deacetylase 3. Histone deacetylase 3 ni Rev erb agonist na probe ntoya ya molekile.Fon taine n'abandi.icyambere, Chemical Book yatangaje ko SR9011 ifitanye isano no gutwika.SR9011 irashobora guhagarika imvugo ya Tr4, bityo igenzura ibimenyetso byokongeza.Intiti z’amahanga zabonye ko muri macrophage y’abantu, kongera imvugo ya mRNA ya SR9011 hakoreshejwe uburyo bwa farumasi biganisha ku kugabanuka kwa mRNA imvugo ya proinflammatory factor interleukin-6.

Mu bushakashatsi bwa vitro:

SR9011 ikoreshwa cyane byongera ibikorwa bya repressor biterwa na REV-ERB byasuzumwe muri selile HEK293 byerekana chimeric Gal4 ADN Binding Domain (DBD) - REV-ERB ligand binding domain (LBD)α or β n'umunyamakuru wa Gal4-yitabira luciferase (REV-ERBα IC 50 = 790 nM, REV-ERBβ IC 50 = 560 nM).SR9011 ihagarika imbaraga kandi neza guhagarika transcription mugusuzuma cotransfection ukoresheje uburebure bwuzuye REV-ERBα hamwe numunyamakuru wa luciferase uyobowe na Bmal1 promoter (SR9011 IC 50 = 620 nM).SR9011 ihagarika imvugo yaBMAL1 mRNA muri selile HepG2 muri REV-ERBα/β -uburyo bushingiye SR9011 ihagarika ikwirakwizwa ryimirongo ya kanseri yamabere utitaye kumiterere ya ER cyangwa HER2.SR9011 isa nkaho ihagarika ingirabuzimafatizo ya kanseri y'ibere mbere yicyiciro cya M.Cyclin A (CCNA2) igaragazwa ko ari gen igamije intego ya REV-ERB yerekana ko guhagarika imvugo ya SR9011 bishobora guhagarika ifatwa ry’akagari.Umuti hamwe na SR9011 bivamo kwiyongera kwingirabuzimafatizo mugice cya G 0 / G 1 no kugabanuka kwingirabuzimafatizo mugice cya S na G 2 / M byerekana ko gukora REV-ERB bishobora gutuma kugabanuka kuva kuri G 1 kugera kuri S na / cyangwa kuva kuri S kugeza G 2 / M icyiciro.

Mu bushakashatsi bwa vivo:

SR9011 Yerekana plasma ifatika, bityo, imvugo ya gen yitabira ya REV-ERB isuzumwa mwumwijima wimbeba zavuwe hamwe na dosiye zitandukanye za SR9011 muminsi 6.Imikorere ya plasminogen inhibitor ubwoko bwa gen 1 (Serpine1) ni gene ya REV-ERB ikanagaragaza ibipimo biterwa no guhagarika imvugo isubiza SR9011. Cholesterol 7α-hydroxylase (Cyp7a1) hamwe na sterol reaction element ihuza proteine ​​(Srepf1) nazo zerekanwe ko zakira REV-ERB kandi zikaba zarahagaritswe no kwiyongera. amafaranga ya SR9011.Nyuma yiminsi 12 muri D: D imiterere yimbeba zatewe inshinge imwe ya SR9011 cyangwa imodoka kuri CT6 (imvugo yo hejuru ya Rev-erbα).Gutera ibinyabiziga ntibitera guhungabana mubikorwa bya moteri.Nyamara, imiyoborere yikinini kimwe cya SR9011 itera gutakaza ibikorwa bya moteri mugihe cyumwijima.Igikorwa gisanzwe gisubiza uruziga rukurikiraho, rujyanye no gukuraho ibiyobyabwenge mugihe kitarenze 24h.Kugabanuka kwa SR9011 kugabanuka kwimyitwarire yimodoka mu mbeba mugihe cyumwijima uhoraho biterwa na dose kandi ko imbaraga (ED 50 = 56 mg / kg) zisa nububasha bwa SR9011-bwahujwe no guhagarika gene yitabira REV-ERB , Srebf1, muri vivo (ED 50 = 67mg / kg).