Incazelo

I-Ribociclib (LEE01) iyi-CDK4/6 inhibitor ecaciswe kakhulu enamanani e-IC50 angu-10 nM no-39 nM, ngokulandelanayo, futhi inamandla angaphansi kokuphindwe izikhathi ezingu-1,000 ngokumelene nenkimbinkimbi ye-cyclin B/CDK1.

Ku-Vitro

Ukwelapha iphaneli yemigqa yeseli ye-neuroblastoma engu-17 nge-Ribociclib (LEE011) kububanzi bethamo lamalogi amane (10 kuya ku-10,000 nM).Ukwelashwa nge-Ribociclib kuvimbela ngokuphawulekayo ukukhula okunamathelayo kwe-substrate okuhlobene nokulawula kwemigqa yeseli ye-neuroblastoma eyi-12 kwangu-17 ehloliwe (kusho i-IC50=306±68 nM, kucatshangelwa imigqa ebucayi kuphela, lapho ukuzwela kuchazwa njenge-IC50 engaphansi kuka-1μUkwelashwa kwe-M. Ribociclib kwemigqa emibili yeseli ye-neuroblastoma (BE2C ne-IMR5) ebonisa ukuzwela ekuvinjweni kwe-CDK4/6 kuphumela ekuqoqweni kwamaseli okuncike kumthamo esigabeni se-G0/G1 somjikelezo weseli.Lokhu kuboshwa kwe-G0/G1 kuba okubalulekile ekugxilweni kwe-Ribociclib okungu-100 nM (p=0.007) no-250 nM (p=0.01), ngokulandelanayo.

Amagundane e-CB17 immunodeficient ane-BE2C, NB-1643 (MYCN amplified, sensitive in vitro), noma EBC1 (non-amplified, resistant in vitro) ama-xenografts aphathwa kanye ngosuku izinsuku ezingu-21 nge-Ribociclib (LEE011; 200 mg/kg) noma nge- ukulawula imoto.Lelisu lokudosa libekezelelwa kahle, njengoba kungekho ukuncipha kwesisindo noma ezinye izimpawu zobuthi ezibonwa kunoma yimaphi amamodeli we-xenograft.Ukukhula kwesimila kubambezeleke kakhulu phakathi nezinsuku ezingama-21 zokwelashwa kumagundane aphethe i-BE2C noma i-1643 xenografts (kokubili, p<0.0001), nakuba ukukhula kuqale kabusha ngemva kokwelashwa.

Isitoreji

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