Tlhaloso

Ribociclib (LEE01) ke CDK4/6 inhibitor e khethehileng haholo e nang le litekanyetso tsa IC50 tsa 10 nM le 39 nM, ka ho latellana, 'me e feta ka makhetlo a 1,000 ka matla a fokolang khahlanong le cyclin B/CDK1 complex.

Ka Vitro

Ho alafa phanele ea lisele tse 17 tsa neuroblastoma ka Ribociclib (LEE011) ho pholletsa le mefuta e mene ea litekanyetso tsa li-log (10 ho isa ho 10,000 nM). Kalafo e nang le Ribociclib e thibela haholo kholo e khomarelang ea substrate e amanang le taolo ho 12 ea 17 ea lisele tsa neuroblastoma tse hlahlobiloeng (ho bolela IC50=306±68 nM, ho nahanoa ka mela e hlokolosi feela, moo kutloisiso e hlalosoang e le IC50 e ka tlase ho 1.μKalafo ea M. Ribociclib ea lisele tse peli tsa neuroblastoma (BE2C le IMR5) e nang le kutloelo-bohloko e bontšitsoeng ho thibelo ea CDK4/6 e fella ka ho bokellana ha lisele tse itšetlehileng ka tekanyo karolong ea G0/G1 ea potoloho ea lisele. Ho ts'oaroa hona ha G0/G1 ho ba bohlokoa ho Ribociclib ea 100 nM (p=0.007) le 250 nM (p=0.01), ka ho latellana.

CB17 immunodeficient litoeba tse nang le BE2C, NB-1643 (MYCN amplified, sensitive in vitro), kapa EBC1 (non-amplified, resistant in vitro) xenografts e tšoaroa hang ka letsatsi bakeng sa matsatsi a 21 ka Ribociclib (LEE011; 200 mg/kg) kapa ka taolo ya koloi. Leano lena la dosing le mamelloa hantle, kaha ha ho tahlehelo ea boima ba 'mele kapa matšoao a mang a chefo a bonoang ho mehlala efe kapa efe ea xenograft. Ho hōla ha hlahala ho lieha haholo ho pholletsa le matsatsi a 21 a phekolo ho litoeba tse nang le BE2C kapa 1643 xenografts (ka bobeli, p <0.0001), le hoja kgolo e ile ea tsosolosa ka mor'a phekolo.

Polokelo

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