Inkcazo

I-Ribociclib (LEE01) i-CDK4 / 6 inhibitor ethile kakhulu kunye ne-IC50 ixabiso le-10 nM kunye ne-39 nM, ngokulandelanayo, kwaye ingaphezulu kwe-1,000-engaphantsi kwamandla angaphantsi kwe-cyclin B / CDK1 complex.

I-In vitro

Ukunyanga ipaneli ye-17 yemigca yeseli ye-neuroblastoma kunye ne-Ribociclib (LEE011) kuluhlu lwedosi ye-log ezine (10 ukuya kwi-10,000 nM).Unyango nge-Ribociclib luthintela ngokubonakalayo ukukhula okubambelelayo kwi-substrate ngokunxulumene nolawulo kwi-12 ye-17 ye-neuroblastoma cell lines ehloliweyo (ithetha i-IC50=306±I-68 nM, ithathela ingqalelo imigca ebuthathaka kuphela, apho ubuntununtunu buchazwa njenge-IC50 engaphantsi kwe-1μUnyango lwe-M. Ribociclib lwemigca emibini yeeseli ze-neuroblastoma (BE2C kunye ne-IMR5) kunye novelwano olubonakalisiweyo kwi-CDK4 / 6 inhibition iphumela ekuqokeleleni okuxhomekeke kwidose kwiiseli kwisigaba se-G0 / G1 somjikelezo weseli.Oku kubanjwa kwe-G0 / G1 kuba yinto ebalulekileyo kwi-Ribociclib concentrations ye-100 nM (p=0.007) kunye ne-250 nM (p=0.01), ngokulandelanayo.

I-CB17 i-immunodeficient iimpuku ezithwala i-BE2C, i-NB-1643 (i-MYCN inyusiwe, i-ective in vitro), okanye i-EBC1 (i-non-amplified, resistant in vitro) i-xenografts iphathwa kanye yonke imihla iintsuku ezingama-21 nge-Ribociclib (LEE011; 200 mg / kg) okanye nge- ulawulo lwesithuthi.Esi sicwangciso se-dosing sinyamezelwa kakuhle, njengoko kungekho kuncipha kwesisindo okanye ezinye iimpawu zetyhefu zibonwa kuyo nayiphi na imodeli ye-xenograft.Ukukhula kwe-tumor kubambezeleke kakhulu kuyo yonke imihla ye-21 yonyango kwiigundane ezigcina i-BE2C okanye i-1643 xenografts (zombini, p <0.0001), nangona ukukhula kwaqala kwakhona emva kokunyanga.

Ugcino

Ubume beMichiza