Ibisobanuro

Ribociclib (LEE01) ni inhibitor yihariye ya CDK4 / 6 ifite indangagaciro ya IC50 ya 10 nM na 39 nM, kandi ikaba ifite inshuro zirenga 1.000 imbaraga nke zirwanya cyclin B / CDK1.

Muri Vitro

Kuvura akanama k’imirongo 17 ya neuroblastoma hamwe na Ribociclib (LEE011) hejuru yimiti ine (10 kugeza 10,000 nM). Umuti hamwe na Ribociclib urabuza cyane gukura kwa substrate gukura ugereranije no kugenzura mumirongo 12 kuri 17 ya selile ya neuroblastoma yasuzumwe (bivuze IC50 = 306±68 nM, urebye imirongo yoroheje gusa, aho sensitivite isobanurwa nka IC50 ya munsi ya 1μM. Ribociclib ivura imirongo ibiri ya selile ya neuroblastoma (BE2C na IMR5) hamwe no kwerekana ko ititaye kuri CDK4 / 6 ituma habaho kwirundanya gukabije kwingirabuzimafatizo mugice cya G0 / G1 cyizunguruka. Ifatwa rya G0 / G1 riba ingirakamaro kuri Ribociclib ya 100 nM (p = 0.007) na 250 nM (p = 0.01).

Imbeba zidafite ubudahangarwa za CB17 zifite BE2C, NB-1643 (MYCN yongerewe imbaraga, yunvikana muri vitro), cyangwa EBC1 (idafite imbaraga, irwanya vitro) ibishushanyo mbonera bivurwa rimwe kumunsi iminsi 21 hamwe na Ribociclib (LEE011; 200 mg / kg) cyangwa hamwe na kugenzura ibinyabiziga. Izi ngamba zo gukuramo zihanganirwa neza, kuko nta kugabanya ibiro cyangwa ibindi bimenyetso byuburozi bigaragara muri bumwe muburyo bwa xenograft. Gukura kw'ibibyimba gutinda cyane muminsi 21 yo kuvura imbeba zifite BE2C cyangwa 1643 xenografts (byombi, p <0.0001), nubwo gukura kwakomeje kuvurwa.

Ububiko

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