Incazelo

I-Lenalidomide (CC-5013) iphuma ku-Thalidomide kanye ne-immunomodulator esebenzayo ngomlomo.I-Lenalidomide (CC-5013) iyi-ligand ye-ubiquitin E3 ligase cereblon (CRBN), futhi ibangela ukukhetha indawo yonke kanye nokucekelwa phansi kwezinto ezimbili ze-lymphoid transcription factor, i-IKZF1 ne-IKZF3, nge-CRBN-CRL4 ubiquitin ligase.I-Lenalidomide (CC-5013) ivimbela ngokuqondile ukukhula kwama-B-cell lymphomas avuthiwe, okuhlanganisa i-myeloma eminingi, futhi yenza ukukhululwa kwe-IL-2 kumaseli T.

Ingemuva

I-Lenalidomide (eyaziwa nangokuthi i-CC-5013), okuphuma ku-thalidomide ngomlomo, i-antineoplastic ejenti ebonisa umsebenzi we-antitumor ngokusebenzisa izindlela ezihlukahlukene, okuhlanganisa ukusebenza kwamasosha omzimba, ukuvinjelwa kwe-angiogenesis, kanye nemiphumela eqondile ye-antineoplastic.Kuye kwacwaningwa kabanzi ekwelapheni i-myeloma eminingi kanye ne-myelodysplastic syndrome kanye nokuphazamiseka kwe-lymphoproliferative okuhlanganisa i-lymphocytic leukemia engapheli (CLL) kanye ne-non-Hodgkin lymphoma.Ngokusho kocwaningo lwakamuva, i-Lnalidomide ikhuthaza futhi ibuyisele ukusebenza kwamasosha omzimba ezigulini ze-CLL ngokufaka ukucindezeleka okukhulu kwama-molecule e-costimulatory kuma-leukemic lymphocytes ukubuyisela ukuzivikela kwe-humoral nokukhiqizwa kwama-immunoglobulins kanye nokwenza ngcono ikhono lamaseli e-T namaseli we-leukemic ukwakha ama-synapses ane-T. ama-lymphocyte.

Ireferensi

Ana Pilar Gonzalez-Rodriguez, Angel R. Payer, Andrea Acebes-Huerta, Leticia Hergo-Zapico, Monica Villa-Alvarez, Esther Gonzalez-Garcia, kanye noSegundo Gonzalez.I-Lenalidomide kanye ne-lymphocytic leukemia engapheli.I-BioMed Research International 2013.

Ku-Vitro

I-Lenalidomide inamandla ekukhuthazeni ukwanda kwama-T cell kanye ne-IFN-γ kanye nokukhiqizwa kwe-IL-2.I-Lenalidomide ikhonjiswe ukuthi ivimbela ukukhiqizwa kwe-pro inflammatory cytokines TNF-α, IL-1, IL-6, IL-12 futhi iphakamise ukukhiqizwa kwe-cytokine elwa nokuvuvukala IL-10 kusuka kuma-PBMC abantu.I-Lenalidomide ilawula ukukhiqizwa kwe-IL-6 ngokuqondile futhi futhi ngokuvimbela amaseli amaningi e-myeloma (MM) kanye nokusebenzisana kwamaseli e-bone marrow stromal (BMSC), okwandisa i-apoptosis yamaseli e-myeloma[2].Ukusebenzisana okuncike kumthamo yinkimbinkimbi ye-CRBN-DDB1 kubonwa nge-Thalidomide, iLenalidomide ne-Pomalidomide, ngamavelu e-IC50 angu-~30μM, ~3μM kanye ~3μM, ngokulandelanayo, Lawa maseli e-CRBN ancishisiwe (U266-CRBN60 kanye ne-U266-CRBN75) asabela kancane kunamaseli abazali emiphumeleni elwa nokwanda kweLenalidomide ebangeni lokuphendula umthamo elingu-0.01 kuye ku-10μM[3].I-Lenalidomide, i-thalidomide analog, isebenza njengeglue yamangqamuzana phakathi kwe-E3 ubiquitin ligase cereblon yomuntu kanye ne-CKI.α kuboniswa ukufaka ubiquitination kanye nokucekelwa phansi kwale kinase, ngaleyo ndlela ngokunokwenzeka ukubulala amangqamuzana e-leukemic ngokusebenza kwe-p53.

Ubuthi bemithamo ye-Lenalidomide bufika ku-15, 22.5, kanye no-45 mg/kg nge-IV, IP, kanye nemizila ye-PO yokuphatha.Kukhawulwe ukuncibilika emotweni yethu yokudosa i-PBS, le mithamo ephezulu efinyelelekayo ye-Lenalidomide ibekezelelwa kahle ngaphandle kokufa kwegundane elilodwa (kwesamba esithathiwe esine) kudosi engu-15 mg/kg IV.Ngokuphawulekayo, abukho obunye ubuthi obubonwayo ocwaningweni kumithamo ye-IV ye-15 mg/kg (n=3) noma 10 mg/kg (n=45) noma kunoma iyiphi enye ileveli yomthamo ngemizila ye-IV, IP, kanye ne-PO.

Isitoreji

Isakhiwo samakhemikhali

Idatha Yebhayoloji Ehlobene

Idatha Yebhayoloji Ehlobene