Saukewa: SR9011REV-ERB neα/βAgonists, membobi na dangin mai karɓar makaman nukiliya, an samo su don daidaita tsarin metabolism na kyallen jikin halitta.Huang Guodong ya gano cewa SR9011 yana taka muhimmiyar rawa wajen daidaita yanayin yanayin halittar ɗan adam na zebrafish autophagy.
Sunadaran iyali na SR9011 ba su da wani yanki mai ɗaure ligand a C-terminal, amma zai iya hana bayyanar furotin Rev erb ta hanyar ɗaukar mai hana mai karɓar nukiliya da histone deacetylase 3. Histone deacetylase 3 shine agonist Rev erb da ƙananan ƙwayoyin ƙwayoyin cuta.Fon taine et al.da farko, Chemicalbook ya ruwaito cewa SR9011 yana da alaƙa da kumburi.SR9011 na iya hana maganganun Tr4, don haka sarrafa siginar kumburi.Masanan kasashen waje sun gano cewa a cikin macrophages na ɗan adam, haɓaka maganganun mRNA na SR9011 ta hanyoyin magunguna kai tsaye yana haifar da raguwar maganganun mRNA na proinflammatory factor interleukin-6.
Nazarin in vitro:
Kashi na SR9011-dogara yana haɓaka ayyukan matsi na dogaro da REV-ERB da aka tantance a cikin sel HEK293 wanda ke bayyana wani yanki na binding na Gal4 DNA (DBD) - REV-ERB ligand binding domain (LBD)α or β da mai ba da rahoto na Luciferase mai amsa Gal4 (REV-ERBα IC 50 = 790 nM, REV-ERBβ IC 50 = 560 nM).SR9011 da ƙarfi kuma cikin inganci yana hana kwafi a cikin kimar cotransfection ta amfani da cikakken tsawon REV-ERBα tare da mai ba da rahoto na luciferase wanda mai tallata Bmal1 (SR9011 IC 50 = 620 nM).SR9011 yana hana bayyanar BMAL1 mRNA a cikin ƙwayoyin HepG2 a cikin REV-ERBα/β Hanyar dogara SR9011 yana hana yaduwar layin ƙwayar nono ko da kuwa matsayin ER ko HER2.SR9011 yana bayyana yana dakatar da zagayowar tantanin halitta na ƙwayoyin kansar nono kafin lokacin M.Cyclin A (CCNA2) an gano shi azaman jigon manufa kai tsaye na REV-ERB yana ba da shawarar cewa kashe furcin wannan cyclin ta SR9011 na iya yin sulhu da kama sake zagayowar tantanin halitta.Jiyya tare da sakamakon SR9011 a cikin karuwa a cikin sel a cikin G 0 / G 1 lokaci da raguwar sel a cikin S da G 2 / M lokaci yana nuna cewa kunnawar REV-ERB na iya haifar da raguwar canji daga G 1 zuwa S. /ko daga S zuwa G 2/M lokaci.
Nazarin vivo:
Saukewa: SR9011 yana nuna ma'auni mai ma'ana na plasma, don haka, ana nazarin maganganun kwayoyin halitta masu amsawa na REV-ERB a cikin hanta na berayen da aka bi da su tare da nau'i-nau'i daban-daban na SR9011 na kwanaki 6. Mai hanawa na plasminogen activator nau'in 1 gene ( Serpine1 ) shine REV-ERB manufa gene. kuma yana nuna ƙaddamar da maganganun da aka dogara da kashi don amsawa ga SR9011. The cholesterol 7a-hydroxylase (Cyp7a1) da kuma sterol amsa sinadaran daurin furotin (Srepf1) an kuma nuna su zama masu amsawa ga REV-ERB kuma an hana su kashi-dogara tare da karuwa. Saukewa: SR9011.Bayan kwanaki 12 a cikin D: D yanayin yanayi ana allurar beraye tare da kashi ɗaya na SR9011 ko abin hawa a CT6 (ƙwaƙwalwar magana na Rev-erbα).Allurar mota ba ta haifar da rushewa a cikin ayyukan locomotor na circadian.Koyaya, gudanar da kashi ɗaya na SR9011 yana haifar da asarar ayyukan locomotor yayin yanayin duhu.Ayyukan al'ada suna dawo da sake zagayowar circadian na gaba, daidai da share magungunan cikin ƙasa da sa'o'i 24.Ragewar dogaro da SR9011 a cikin halayen gudu a cikin ɓeraye a ƙarƙashin yanayin duhu akai-akai ya dogara da kashi kuma ƙarfin (ED 50 = 56 mg/kg) yayi kama da ƙarfin SR9011-matsakaici na kawar da kwayar cutar ta REV-ERB. , Srebf1, a cikin vivo (ED 50 = 67mg/kg).
Lokacin aikawa: Dec-06-2022