Tsanangudzo

Lenalidomide (CC-5013) inotorwa kubva kuThalidomide uye nemuromo inoshanda immunomodulator. Lenalidomide (CC-5013) is a ligand ye ubiquitin E3 ligase cereblon (CRBN), uye inokonzera kusarudzwa kwekugara uye kuora kweviri lymphoid transcription factor, IKZF1 uye IKZF3, neCRBN-CRL4 ubiquitin ligase. Lenalidomide (CC-5013) inonyanya kurambidza kukura kweB-cell lymphomas yakakura, kusanganisira multiple myeloma, uye inokonzera IL-2 kusunungurwa kubva kuT masero.

Background

Lenalidomide (inozivikanwawo seCC-5013), inotorwa nemuromo yethalidomide, is an antineoplastic agent inoratidza antitumor chiitiko kuburikidza nenzira dzakasiyana siyana, kusanganisira immune system activation, angiogenesis inhibition, uye yakananga antineoplastic mhedzisiro. Yakave yakadzidzwa zvakanyanya pakurapa kwemultiple myeloma uye myelodysplastic syndrome pamwe nezvirwere zve lymphoproliferative zvinosanganisira chronic lymphocytic leukemia (CLL) uye isiri Hodgkin lymphoma. Zvinoenderana nezvidzidzo zvichangobva kuitika, Lnalidomide inosimudzira uye kudzoreredza immune system kushanda muvarwere veCLL nekuita kuti kuwedzeredza kwemamorekuru anodhura muleukemic lymphocytes kudzoreredza humoral immune immune uye kugadzirwa kwema immunoglobulins pamwe nekuvandudza kugona kweT masero uye leukemic masero kugadzira synapses neT. lymphocytes.

Reference

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

In Vitro

Lenalidomide ine simba mukukurudzira T cell kuwanda uye IFN-γ uye IL-2 kugadzirwa. Lenalidomide yakaratidza kurambidza kugadzirwa kwepro inflammatory cytokines TNF-α, IL-1, IL-6, IL-12 uye inosimudzira kugadzirwa kwe-anti-inflammatory cytokine IL-10 kubva kuPBMC yevanhu. Lenalidomide inoderedza kugadzirwa kweIL-6 zvakananga uye zvakare nekudzivisa akawanda myeloma (MM) masero uye bone marrow stromal masero (BMSC) kuwirirana, izvo zvinowedzera apoptosis ye myeloma masero [2]. Dose-inotsamira yekudyidzana neCRBN-DDB1 yakaoma inoonekwa neThalidomide, Lenalidomide uye Pomalidomide, ine IC50 kukosha kwe ~30.μM, ~3μM uye ~3μM, zvakateerana, Aya akaderedzwa CRBN kutaura maseru (U266-CRBN60 uye U266-CRBN75) haanyanyi kuterera kupfuura maseru evabereki kune antiproliferative mhedzisiro Lenalidomide pane iyo dose-mhinduro renji ye0.01 kusvika 10μM[3]. Lenalidomide, thalidomide analog, inoshanda semolecular glue pakati pemunhu E3 ubiquitin ligase cereblon uye CKI.α inoratidzwa kuti iite kuti ubiquitination uye kuderedzwa kwekinase iyi, saka zvichida kuuraya masero eukemic ne p53 activation.

Kuchetura kweLenalidomide kunosvika ku15, 22.5, uye 45 mg/kg kuburikidza neIV, IP, uye PO nzira dzekutonga. Yakaganhurirwa nekunyungudika mumotokari yedu yePBS dosing, aya madhizimu anogoneka eLenalidomide anoshivirirwa zvakanaka kunze kwekufa kwembeva imwe chete (yechina yakazara dosed) pa15 mg/kg IV dose. Zvinonzwisisika, hapana humwe huturu hunocherechedzwa muchidzidzo paIV doses ye15 mg/kg (n=3) kana 10 mg/kg (n=45) kana chero imwe nhanho yedosi kuburikidza neIV, IP, uye PO nzira.

Storage

Chimiro chemakemikari

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