SR9011 CAS 1379686-29-9 KUFUFUZA

SR9011ndi REV-ERBα/βAgonists, mamembala a banja la zida za nyukiliya, apezeka kuti amayang'anira kagayidwe kazinthu zamoyo.Huang Guodong adapeza kuti SR9011 imagwira ntchito yofunikira pakuwongolera kayimbidwe ka jini ya zebrafish autophagy.

Mapuloteni a banja la SR9011 alibe malo omangira ligand pa C-terminal, koma akhoza kulepheretsa kufotokoza kwa mapuloteni a Rev erb polemba nyukiliya receptor inhibitor ndi histone deacetylase 3. Histone deacetylase 3 ndi Rev erb agonist ndi kafukufuku wamankhwala ang'onoang'ono a molekyulu.Fon taine et al.Choyamba, Chemicalbook inanena kuti SR9011 ili ndi mgwirizano ndi kutupa.SR9011 imatha kuletsa mawu a Tr4, motero kuwongolera chizindikiro chotupa.Akatswiri akunja apeza kuti mu macrophages aumunthu, kukulitsa mawu a mRNA a SR9011 mwa njira zamankhwala kumabweretsa kuchepa kwa mawu a mRNA a proinflammatory factor interleukin-6.

Maphunziro a in vitro:

Mlingo wa SR9011 umachulukitsa ntchito yopondereza yodalira REV-ERB yomwe imayesedwa m'maselo a HEK293 akuwonetsa chimeric Gal4 DNA Binding Domain (DBD) - REV-ERB ligand binding domain (LBD)α or β ndi mtolankhani wa Gal4-responsive luciferase (REV-ERBα IC 50 =790 nM, REV-ERBβ IC 50 = 560 nM).SR9011 imapondereza mwamphamvu komanso moyenera kulembedwa mu kuyesa kwa cotransfection pogwiritsa ntchito kutalika kwa REV-ERBα pamodzi ndi mtolankhani wa luciferase woyendetsedwa ndi Bmal1 wolimbikitsa (SR9011 IC 50 = 620 nM).SR9011 imapondereza mawu aBMAL1 mRNA m'maselo a HepG2 mu REV-ERBα/β -njira yodalira SR9011 imapondereza kuchuluka kwa ma cell a khansa ya m'mawere mosasamala kanthu za ER kapena HER2.SR9011 ikuwoneka kuti imayimitsa kuzungulira kwa ma cell a khansa ya m'mawere gawo la M lisanachitike.Cyclin A (CCNA2) imadziwika ngati jini yolunjika ya REV-ERB kutanthauza kuti kupondereza mawu a cyclin ndi SR9011 kungayambitse kumangidwa kwa cell.Kuchiza ndi SR9011 kumabweretsa kuwonjezeka kwa maselo mu gawo la G 0 / G 1 ndi kuchepa kwa maselo mu gawo la S ndi G 2 / M kutanthauza kuti kutsegula kwa REV-ERB kungayambitse kuchepa kwa kusintha kuchokera ku G 1 kupita ku gawo la S ndi / kapena kuchokera ku S kupita ku G2 /M gawo.

Maphunziro a vivo:

SR9011 amasonyeza kuwonetseredwa kwa plasma koyenera, motero, mafotokozedwe a majeremusi omvera a REV-ERB amafufuzidwa mu chiwindi cha mbewa zomwe zimatengedwa ndi mitundu yosiyanasiyana ya SR9011 kwa masiku a 6. The plasminogen activator inhibitor type 1 jini (Serpine1) ndi REV-ERB jini yowunikira. ndipo amasonyeza kuponderezedwa kwa mawu odalira mlingo poyankha SR9011. Cholesterol 7α-hydroxylase (Cyp7a1) ndi sterol response element kumanga mapuloteni (Srepf1) majini asonyezedwanso kuti amamvera REV-ERB ndipo amaponderezedwa modalira mlingo ndi kuwonjezeka. Mtengo wa SR9011.Pambuyo pa masiku a 12 mu D: D mikhalidwe mbewa zimayikidwa ndi mlingo umodzi wa SR9011 kapena galimoto pa CT6 (mawonekedwe apamwamba a Rev-erbα).Jakisoni wamagalimoto sayambitsa kusokoneza kwa circadian locomotor ntchito.Komabe, kugwiritsa ntchito mlingo umodzi wa SR9011 kumabweretsa kutayika kwa ntchito ya locomotor panthawi yamdima wamutu.Kuchita mwachizolowezi kumabweretsanso kuzungulira kwanthawi kotsatira, kogwirizana ndi chilolezo chamankhwala pasanathe maola 24.Kutsika kodalira kwa SR9011 mumayendedwe oyendetsa magudumu mu mbewa pansi pamikhalidwe yamdima nthawi zonse kumadalira mlingo komanso kuti potency (ED 50 = 56 mg / kg) ndi yofanana ndi mphamvu ya SR9011-mediated kuponderezedwa kwa REV-ERB jini yomvera. , Srebf1 , mu vivo (ED 50 = 67mg/kg).