SR9011 CAS 1379686-29-9 Nchọpụta

SR9011bụ REV-ERBα/βAchọtala ndị na-eme ihe ike, bụ́ ndị òtù ezinụlọ na-anata ngwá agha nuklia, na-achịkwa metabolism nke anụ ahụ ndị dị ndụ.Huang Guodong chọpụtara na SR9011 na-arụ ọrụ dị mkpa n'ịchịkwa ụda nke mkpụrụ ndụ ihe nketa nke zebrafish autophagy.

Ndị na-edozi ezinụlọ SR9011 enweghị ngalaba njikọ njikọ ligand na C-terminal, mana nwere ike igbochi nkwupụta nke protein Rev erb site n'ịweta ndị na-eme ihe nchịkwa nuklia na histone deacetylase 3. Histone deacetylase 3 bụ agonist Rev erb na obere nyocha kemịkalụ molecule.Fon taine et al.Nke mbụ, Chemicalbook kọrọ na SR9011 nwere njikọ na mbufụt.SR9011 nwere ike igbochi okwu nke Tr4, si otú a na-achịkwa mgbaàmà mkpali.Ndị ọkà mmụta si mba ọzọ achọpụtala na na macrophages mmadụ, ịba ụba okwu mRNA nke SR9011 site na usoro ọgwụ na-eduga ozugbo na mbelata mRNA okwu nke proinflammatory factor interleukin-6.

Ọmụmụ in vitro:

SR9011 dose-dabere na-abawanye ọrụ mmegide na-adabere na REV-ERB nke a na-enyocha na sel HEK293 na-egosipụta ngalaba chimeric Gal4 DNA Binding (DBD) - REV-ERB ligand binding domain (LBD)α or β na onye nta akụkọ luciferase Gal4 na-anabata (REV-ERBα IC 50 = 790 nM, REV-ERBβ IC 50 = 560 nM).SR9011 nke ọma na nke ọma na-egbochi ndebanye aha na nyocha cotransfection site na iji REV-ERB zuru oke.α tinyere onye nta akụkọ luciferase nke Bmal1 kwalitere (SR9011 IC 50 = 620 nM).SR9011 na-egbochi okwu BMAL1 mRNA na sel HepG2 na REV-ERBα/β -adabere n'ụzọ SR9011 na-egbochi mmụba nke ahịrị mkpụrụ ndụ kansa ara n'agbanyeghị ọkwa ER ma ọ bụ HER2 ha.SR9011 dị ka ọ na-akwụsịtụ okirikiri cell nke mkpụrụ ndụ kansa ara tupu oge M.Achọpụtara Cyclin A (CCNA2) dị ka mkpụrụ ndụ ebumnuche ebumnuche kpọmkwem nke REV-ERB na-atụ aro na nbibi okwu nke cyclin a site na SR9011 nwere ike mebie njide okirikiri cell.Ọgwụgwọ na SR9011 na-ebute mmụba nke mkpụrụ ndụ na mpaghara G 0 / G 1 yana mbelata nke mkpụrụ ndụ na S na G 2 / M na-atụ aro na ịgbalite REV-ERB nwere ike bute mbelata mgbanwe site na G 1 ruo S. / ma ọ bụ site na S ruo G 2 / M nkeji.

Ọmụmụ ihe na vivo:

SR9011 na-egosiputa ihe ngosi plasma ezi uche dị na ya, ya mere, a na-enyocha okwu nke mkpụrụ ndụ ihe nketa REV-ERB na imeju ụmụ oke na-eji usoro dị iche iche nke SR9011 mee ihe maka ụbọchị 6. Ụdị plasminogen activator inhibitor ụdị 1 gene (Serpine1) bụ ihe mgbaru ọsọ REV-ERB. ma na-egosiputa nkwụsịtụ nke na-adabere na dose na nzaghachi na SR9011. The cholesterol 7a-hydroxylase (Cyp7a1) na sterol nzaghachi element na-ejikọta protein (Srepf1) ka egosikwara na ọ na-anabata REV-ERB ma na-adabere na dose-dabere na-ebelata na ịba ụba. Ọnụahịa kasị elu nke SR9011.Mgbe ụbọchị iri na abụọ gasịrị na D: D ọnọdụ a na-agbanye ụmụ oke na otu dose nke SR9011 ma ọ bụ ụgbọ ala na CT6 (okwu kachasị elu nke Rev-erbα).Ngwunye ụgbọ ala anaghị akpata ọgba aghara na ọrụ locomotor circadian.Agbanyeghị, nchịkwa otu dose nke SR9011 na-ebute mfu nke ọrụ locomotor n'oge isiokwu gbara ọchịchịrị.Ọrụ nkịtị na-eweghachi okirikiri circadian na-esote, kwekọrọ na mkpochapụ ọgwụ n'ihe na-erughị awa 24.Mbelata SR9011 na-adabere na omume ịgba ọsọ wheel na ụmụ oke n'okpuru ọnọdụ ọchịchịrị mgbe niile na-adabere na dose na ike ahụ (ED 50 = 56 mg/kg) yiri ike nke SR9011-mediated suppression of a REV-ERB gene responsive gene. , Srebf1, na vivo (ED 50 = 67mg / kg).