Kufotokozera

Lenalidomide (CC-5013) ndi yochokera ku Thalidomide ndi pakamwa yogwira immunomodulator.Lenalidomide (CC-5013) ndi ligand ya ubiquitin E3 ligase cereblon (CRBN), ndipo imayambitsa kusankha kokhazikika komanso kuwonongeka kwa zinthu ziwiri zolembera za lymphoid, IKZF1 ndi IKZF3, ndi CRBN-CRL4 ubiquitin ligase.Lenalidomide (CC-5013) makamaka imalepheretsa kukula kwa B-cell lymphomas okhwima, kuphatikizapo angapo myeloma, ndipo imapangitsa IL-2 kumasulidwa ku T ma cell.

Mbiri

Lenalidomide (yomwe imadziwikanso kuti CC-5013), yochokera pakamwa ya thalidomide, ndi antitineoplastic agent yomwe imasonyeza ntchito ya antitumor kudzera m'njira zosiyanasiyana, kuphatikizapo chitetezo cha mthupi, angiogenesis inhibition, ndi zotsatira za antineoplastic mwachindunji.Zaphunziridwa kwambiri pochiza matenda ambiri a myeloma ndi myelodysplastic komanso matenda a lymphoproliferative kuphatikizapo chronic lymphocytic leukemia (CLL) ndi non-Hodgkin lymphoma.Malinga ndi kafukufuku waposachedwa, Lnalidomide imalimbikitsa ndikubwezeretsa chitetezo cham'thupi mwa odwala CLL mwa kuchititsa kuti ma molekyulu a costimulatory mu leukemic lymphocytes abwezeretse chitetezo chokwanira komanso kupanga ma immunoglobulins komanso kupititsa patsogolo luso la maselo a T ndi maselo a leukemic kupanga ma synapses ndi T. ma lymphocytes.

Buku

Ana Pilar Gonzalez-Rodriguez, Angel R. Payer, Andrea Acebes-Huerta, Leticia Hergo-Zapico, Monica Villa-Alvarez, Esther Gonzalez-Garcia, ndi Segundo Gonzalez.Lenalidomide ndi matenda a lymphocytic leukemia.BioMed Research International 2013.

Mu Vitro

Lenalidomide ndi yamphamvu polimbikitsa kuchuluka kwa T cell ndi IFN-γ ndi kupanga IL-2.Lenalidomide yasonyezedwa kuti imalepheretsa kupanga ma pro inflammatory cytokines TNF-α, IL-1, IL-6, IL-12 ndikukweza kupanga anti-inflammatory cytokine IL-10 kuchokera ku PBMC zaumunthu.Lenalidomide imachepetsa kupanga IL-6 mwachindunji komanso poletsa ma cell angapo a myeloma (MM) ndi ma cell marrow stromal cell (BMSC), omwe amawonjezera apoptosis ya maselo a myeloma [2].Kugwirizana kodalira mlingo ndi CRBN-DDB1 zovuta kumawonedwa ndi Thalidomide, Lenalidomide ndi Pomalidomide, ndi IC50 values ​​of ~30μm, ~3μM ndi ~3μM, motero, Maselo afupikitsa a CRBN (U266-CRBN60 ndi U266-CRBN75) samvera kwambiri kusiyana ndi maselo a makolo ku zotsatira za antiproliferative Lenalidomide kudutsa mlingo-mayankho osiyanasiyana a 0.01 mpaka 10μM[3].Lenalidomide, analogi ya thalidomide, imagwira ntchito ngati guluu molekyulu pakati pa E3 ubiquitin ligase cereblon ndi CKI.α akuwonetsedwa kuti apangitse kufalikira ndi kuwonongeka kwa kinase iyi, motero kupha maselo a leukemic ndi p53 activation.

Kawopsedwe wa Mlingo wa Lenalidomide mpaka 15, 22.5, ndi 45 mg/kg kudzera munjira za IV, IP, ndi PO.Zochepa chifukwa cha kusungunuka mu galimoto yathu ya dosing ya PBS, Mlingo wapamwamba kwambiri wa Lenalidomide uwu umaloledwa bwino kupatula kufa kwa mbewa imodzi (yomwe ili ndi mlingo umodzi) pa mlingo wa 15 mg/kg IV.Makamaka, palibe poizoni wina yemwe amawonedwa mu kafukufuku wa IV wa 15 mg/kg (n=3) kapena 10 mg/kg (n=45) kapena pamlingo wina uliwonse kudzera munjira za IV, IP, ndi PO.

Kusungirako

Kapangidwe ka mankhwala

Related Biological Data

Related Biological Data