wehewehe

ʻO Ribociclib (LEE01) kahi mea hoʻopaneʻe CDK4/6 kikoʻī loa me nā koina IC50 o 10 nM a me 39 nM, kēlā me kēia, a ʻoi aku ma mua o 1,000-fold ka liʻiliʻi o ka ikaika e kūʻē i ka paʻakikī cyclin B/CDK1.

In Vitro

Ka mālama ʻana i kahi papa o 17 neuroblastoma cell lines me Ribociclib (LEE011) ma kahi ʻehā-log dose range (10 a 10,000 nM).ʻO ka hoʻomaʻamaʻa ʻana me Ribociclib e kāohi nui i ka ulu ʻana o ka substrate adherent e pili ana i ka mana ma 12 o nā laina cell neuroblastoma 17 i nānā ʻia (mean IC50=306±68 nM, e noʻonoʻo ana i nā laina koʻikoʻi wale nō, kahi i wehewehe ʻia ai ka naʻau ma ke ʻano he IC50 o lalo o 1.μʻO M. Ribociclib ka mālama ʻana i nā laina cell neuroblastoma ʻelua (BE2C a me IMR5) me ka hōʻike ʻana i ka naʻau i ka CDK4 / 6 inhibition hopena i ka hōʻiliʻili ʻana i ka nui o nā cell i loko o ka pae G0 / G1 o ka pōʻai cell.Ua lilo kēia hopu G0 / G1 i mea koʻikoʻi ma Ribociclib nā manaʻo o 100 nM (p = 0.007) a me 250 nM (p = 0.01), i kēlā me kēia.

CB17 immunodeficient mice e lawe ana i ka BE2C, NB-1643 (MYCN amplified, sensitive in vitro), a i ʻole EBC1 (non-amplified, resistant in vitro) xenografts e mālama ʻia i hoʻokahi lā i kēlā me kēia lā no 21 mau lā me Ribociclib (LEE011; 200 mg/kg) a i ʻole me kahi kaʻa kaʻa.ʻAʻole ʻae ʻia kēia hoʻolālā dosing, no ka mea, ʻaʻole ʻike ʻia ka pohō kaumaha a i ʻole nā ​​​​hōʻailona ʻē aʻe o ka ʻona i kekahi o nā kumu hoʻohālike xenograft.Hoʻopaneʻe nui ʻia ka ulu ʻana o ka tumor i nā lā 21 o ka mālama ʻana i nā ʻiole e mālama ana i ka BE2C a i ʻole 1643 xenografts (ʻelua, p<0.0001), ʻoiai ua hoʻomau ka ulu ʻana ma hope o ka mālama ʻana.

Waihona

ʻO ke kinona