| Kev tshawb nrhiav hauv vitro | Sunitinib muaj txiaj ntsig zoo hauv inhibiting Kit thiab FLT-3. Sunitinib yog ib qho zoo ATP kev sib tw inhibitor ntawm VEGFR2 (Flk1) thiab PDGFRβ, KI yog 9 nM thiab 8 nM feem, ua haujlwm ntawm VEGFR2 thiab PDGFR zoo dua FGFR-1, EGFR, Cdk2, Met, IGFR-1, Abl, thiab src xaiv tau ntau dua 10 npaug. Hauv cov ntshav qab zib NIH-3T3 hlwb qhia VEGFR2 lossis PDGFRβ, Sunitinib inhibited VEGF-dependent VEGFR2 phosphorylation thiab PDGF-dependent PDGFRβ phosphorylation nrog IC50 ntawm 10 nM thiab 10 nM, feem. Rau NIH-3T3 hlwb overexpressing PDGFRβ los yog PDGFRα, Sunitinib inhibited proliferation induced los ntawm VEGF nrog ib tug IC50 ntawm 39 nM thiab 69 nM, feem. Sunitinib inhibited hom tsiaj qus FLT3, FLT3-ITD, thiab FLT3-Asp835 phosphorylation nrog IC50 ntawm 250 nM, 50 nM, thiab 30 nM, feem. Sunitinib inhibited kev loj hlob ntawm MV4; 11 thiab OC1-AML5 hlwb nrog IC50 ntawm 8 nM thiab 14 nM, raws li, thiab induced apoptosis nyob rau hauv ib koob tshuaj. |
| Hauv vivo kawm | Raws li qhov tseem ceeb, xaiv inhibition ntawm phosphorylation thiab teeb liab ntawm VEGFR2 lossis PDGFR hauv vivo, Sunitinib (20-80 mg / kg / hnub) tau pom tias yog lub luag haujlwm rau ntau yam qog xenograft qauv, suav nrog HT-29, A431, Colo205, h -460, SF763T, C6, A375, lossis MDA-MB-435 tau nthuav tawm dav dav ntawm kev siv tshuaj tiv thaiv kab mob. Sunitinib ntawm koob tshuaj 80 mg / kg / hnub rau 21 hnub tau ua tiav cov qog regression hauv 6 ntawm 8 nas, thiab thaum kawg ntawm kev kho mob, cov qog tsis rov tsim dua thaum lub sijhawm soj ntsuam 110 hnub. Qhov thib ob ntawm kev kho mob nrog Sunitinib tseem muaj txiaj ntsig zoo rau cov qog nqaij hlav, tab sis tsis zoo tag nrho los ntawm thawj qhov kev kho mob. Kev kho Sunitinib ua rau muaj qhov txo qis hauv qog MVD, uas tau txo qis los ntawm ~ 40% hauv SF763T gliomas. SU11248 kev kho mob tau ua tiav inhibition ntawm cov qog loj hlob ntxiv ntawm luciferase-expressing PC-3M xenografts, txawm hais tias tsis muaj qhov txo qis hauv qog loj. Hauv FLT3-ITD tus qauv hloov cov pob txha pob txha, kev kho Sunitinib (20 mg / kg / hnub) cuam tshuam qhov kev loj hlob ntawm subcutaneous MV4; 11 (FLT3-ITD) xenografts thiab ntev ciaj sia taus. |
