Fa'amatalaga

Ribociclib (LEE01) o se CDK4 / 6 faʻapitoa faʻapitoa faʻatasi ma IC50 tau o 10 nM ma 39 nM, i le faasologa, ma e sili atu i le 1,000-faʻaitiitia le malosi e faasaga i le cyclin B / CDK1 complex.

I Vitro

Togafitiga o se vaega o 17 neuroblastoma laina sela ma Ribociclib (LEE011) i luga o le fa-log dose laina (10 i 10,000 nM). Togafitiga faʻatasi ma Ribociclib e matua faʻalavelaveina le tuputupu aʻe o le substrate e faʻatatau i le puleaina i le 12 o le 17 neuroblastoma laina sela na suʻesuʻeina (o lona uiga IC50=306±68 nM, mafaufau i laina maaleale, pe a faʻamatalaina le maaleale o se IC50 e itiiti ifo i le 1μM. Ribociclib togafitiga o laina cell neuroblastoma e lua (BE2C ma IMR5) faʻatasi ai ma le faʻaalia o le faʻaogaina o le CDK4 / 6 faʻalavelave e maua ai le faʻaputuga faʻalagolago o sela i le vaega G0 / G1 o le taamilosaga sela. O lenei G0 / G1 puʻeina e avea ma mea taua i Ribociclib concentrations o 100 nM (p = 0.007) ma 250 nM (p = 0.01), i le faasologa.

CB17 immunodeficient isumu o loʻo tauaveina BE2C, NB-1643 (MYCN faʻateleina, maʻaleʻale i vitro), poʻo EBC1 (e le faʻamalosia, faʻasalaina in vitro) xenografts e togafitia faʻatasi i aso uma mo 21 aso ma Ribociclib (LEE011; 200 mg / kg) poʻo se pulea taavale. O lenei ta'iala ole tui e lelei ona talia, aua e leai se pa'u mamafa po'o isi fa'ailoga ole oona e matauina i so'o se fa'ata'ita'iga xenograft. O le tuputupu aʻe o le Tumor e matua tuai lava i le 21 aso o togafitiga i isumu o loʻo teuina le BE2C poʻo le 1643 xenografts (lua, p<0.0001), e ui lava na toe faʻaauau le tuputupu aʻe pe a maeʻa togafitiga.

Teuina

Fa'asologa o vaila'au