Kufotokozera

Ribociclib (LEE01) ndi CDK4/6 inhibitor yodziwika bwino yokhala ndi IC50 milingo ya 10 nM ndi 39 nM, motsatana, ndipo ili ndi mphamvu zopitilira 1,000 motsutsana ndi cyclin B/CDK1.

Mu Vitro

Kuchiza gulu la mizere 17 ya ma cell a neuroblastoma ndi Ribociclib (LEE011) pamlingo wamitengo inayi (10 mpaka 10,000 nM). Kuchiza ndi Ribociclib kumalepheretsa kukula kotsatira kwa gawo lapansi poyerekeza ndi kuwongolera mu 12 mwa 17 ma cell a neuroblastoma omwe ayesedwa (kutanthauza IC50=306).±68 nM, poganizira mizere yovuta yokha, pomwe kukhudzika kumatanthauzidwa ngati IC50 yochepera 1μKuchiza kwa M. Ribociclib kwa mizere iwiri ya neuroblastoma cell (BE2C ndi IMR5) ndikuwonetsa kukhudzidwa kwa CDK4/6 kulepheretsa kumabweretsa kuchulukidwa kwa maselo motengera mlingo mu gawo la G0/G1 la cell cycle. Kumangidwa kwa G0/G1 kumakhala kofunika kwambiri pa Ribociclib ndende ya 100 nM (p=0.007) ndi 250 nM (p=0.01), motsatira.

CB17 immunodeficient mbewa zokhala ndi BE2C, NB-1643 (MYCN amplified, sensitive in vitro), kapena EBC1 (non-amplified, resistant in vitro) xenografts amathandizidwa kamodzi tsiku lililonse kwa masiku 21 ndi Ribociclib (LEE011; 200 mg/kg) kapena kuwongolera magalimoto. Njira iyi ya dosing imalekerera bwino, chifukwa palibe kuwonda kapena zizindikiro zina za poizoni zomwe zimawonedwa mumitundu iliyonse ya xenograft. Kukula kwa chotupa kumachedwa kwambiri m'masiku onse a 21 a chithandizo mu mbewa zokhala ndi BE2C kapena 1643 xenografts (onse, p<0.0001), ngakhale kuti kukula kunayambiranso pambuyo pa chithandizo.

Kusungirako

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