SR9011 CAS 1379686-29-9 NUI

SR9011he REV-ERBα/βUa ʻike ʻia nā Agonists, nā lālā o ka ʻohana nuklear receptor, e hoʻoponopono i ka metabolism o nā mea olaola.Ua ʻike ʻo Huang Guodong he kuleana koʻikoʻi ka SR9011 i ka hoʻoponopono ʻana i ke kani o ka zebrafish autophagy gene.

ʻAʻole i loaʻa i nā protein ʻohana SR9011 kahi ligand binding domain ma ka C-terminal, akā hiki ke kāohi i ka hōʻike ʻana o Rev erb protein ma ke kiʻi ʻana i ka mea hoʻopaneʻe nuklea a me ka histone deacetylase 3. ʻO ka histone deacetylase 3 he Rev erb agonist a me kahi moleke liʻiliʻi.Fon taine et al.ʻO ka mea mua, ua hōʻike ʻo Chemicalbook e pili ana ka SR9011 me ka mumū.Hiki i ka SR9011 ke kāohi i ka hōʻike ʻana o Tr4, pēlā e hoʻomalu ai i ka hōʻailona inflammatory.Ua ʻike nā haumāna haole i loko o nā macrophages kanaka, hoʻonui i ka hōʻike mRNA o SR9011 e nā ʻano pharmacological e alakaʻi pololei i ka emi ʻana o ka hōʻike mRNA o ka mea proinflammatory interleukin-6.

Haʻawina in vitro:

Hoʻonui ka nui o ka SR9011 i ka hana repressor hilinaʻi REV-ERB i loiloi ʻia ma nā cell HEK293 e hōʻike ana i kahi chimeric Gal4 DNA Binding Domain (DBD) - REV-ERB ligand binding domain (LBD)α or β a me kahi mea hoʻolaha luciferase pane Gal4 (REV-ERBα IC 50 =790 nM, REV-ERBβ IC 50 =560 nM).Hoʻopau ikaika ʻo SR9011 i ka transcription i loko o kahi cotransfection assay me ka hoʻohana ʻana i ka REV-ERB holoʻokoʻa.α me kahi mea hoʻolaha luciferase i alakaʻi ʻia e ka mea hoʻolaha Bmal1 (SR9011 IC 50 = 620 nM).Kāohi ʻo SR9011 i ka hōʻike ʻana o BMAL1 mRNA i nā cell HepG2 i kahi REV-ERBα/β Hoʻopau ʻo SR9011 i ka hoʻonui ʻana o nā laina kelepona maʻi umauma me ka nānā ʻole i ko lākou kūlana ER a i ʻole HER2.ʻIke ʻia ʻo SR9011 e hoʻomaha i ka pōʻai cell o nā maʻi maʻi maʻi umauma ma mua o ka pae M.ʻIke ʻia ʻo Cyclin A (CCNA2) ma ke ʻano he kiko kuhikuhi pololei o REV-ERB e hōʻike ana i ka hoʻopau ʻana i ka hōʻike ʻana o kēia cyclin e SR9011 hiki ke hoʻopaʻa i ka hopu ʻana o ke kaʻina cell.ʻO ka lapaʻau ʻana me SR9011 ka hopena i ka piʻi ʻana o nā cell i loko o ka pae G 0 / G 1 a me ka emi ʻana o nā cell ma ka pae S a me G 2 / M e hōʻike ana i ka hoʻāla ʻana o REV-ERB e hopena i ka hoʻemi ʻana o ka hoʻololi ʻana mai G 1 a i ka pae S a /aiʻole mai S a G 2 /M māhele.

Ke aʻo ʻana ma vivo:

SR9011 hōʻike i ka hōʻike plasma kūpono, no laila, nānā ʻia ka ʻōlelo o REV-ERB pane pane i loko o ke akepaʻa o nā ʻiole i mālama ʻia me nā ʻano like ʻole o SR9011 no nā lā 6. ʻO ka plasminogen activator inhibitor type 1 gene ( Serpine1 ) he REV-ERB target gene a hōʻike i ka hoʻopau ʻana i ka hoʻopaʻa ʻana i ka hōʻike ma ka pane ʻana iā SR9011. Ua hōʻike pū ʻia nā genes cholesterol 7α-hydroxylase (Cyp7a1) a me ka sterol response element binding protein (Srepf1) i ka REV-ERB a ua kāohi ʻia me ka hoʻonui ʻana. huina o SR9011.Ma hope o 12 mau lā ma D: D mau ʻiole e hoʻokomo ʻia nā ʻiole me ka nui o SR9011 a i ʻole kaʻa ma CT6 (ka ʻōlelo kiʻekiʻe o Rev-erbα).ʻAʻole hoʻopilikia ʻia ka hana locomotor circadian.Eia nō naʻe, ʻo ka hoʻohana ʻana i hoʻokahi maʻa o SR9011 ka hopena i ka nalowale o ka hana locomotor i ka wā o ke kumuhana pōʻeleʻele.Hoʻihoʻi ka hana maʻamau i ka pōʻai circadian aʻe, e kūlike me ka hoʻomaʻemaʻe ʻana i nā lāʻau lapaʻau ma lalo o 24h.ʻO ka emi ʻana o ka SR9011 i ka holo ʻana o ka huila i nā ʻiole ma lalo o ka pōʻeleʻele mau e pili ana i ka dose a ʻo ka mana (ED 50 = 56 mg / kg) like me ka mana o SR9011-mediated suppression o kahi REV-ERB pane pane. , Srebf1 , in vivo (ED 50 =67mg/kg).