Ibisobanuro

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

Muri Vitro

Kuvura akanama kamwe ka selile 17 ya neuroblastoma hamwe na Ribociclib (LEE011) murwego rwibiti bine (10 kugeza 10,000 nM).Umuti hamwe na Ribociclib urabuza cyane gukura kwa substrate gukura ugereranije no kugenzura muri 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 neuroblastoma (BE2C na IMR5) hamwe no kwerekana ko ititaye kuri CDK4 / 6 ituma habaho kwiyegeranya kwinshi kwingirabuzimafatizo mugice cya G0 / G1 cyinzira ya selile.Ifatwa rya G0 / G1 riba ingirakamaro kuri Ribociclib ya 100 nM (p = 0.007) na 250 nM (p = 0.01).

Imbeba ya immunodeficient ya CB17 ifite 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 gutakaza ibiro cyangwa ibindi bimenyetso byuburozi bigaragara muri buri bwoko bwa xenograft.Gukura kw'ibibyimba gutinda cyane muminsi 21 yo kuvura imbeba zifata amashusho ya BE2C cyangwa 1643 (byombi, p <0.0001), nubwo gukura byongeye kuvurwa.

Ububiko

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