Tlhaloso

Lenalidomide (CC-5013) ke motsoako oa Thalidomide le immunomodulator e sebetsang ka molomo. Lenalidomide (CC-5013) ke ligand tsa ubiquitin E3 ligase cereblon (CRBN), 'me e baka ho khetha hohle le ho senyeha ha lintlha tse peli tsa transcription tsa lymphoid, IKZF1 le IKZF3, ka CRBN-CRL4 ubiquitin ligase. Lenalidomide (CC-5013) ka ho khetheha e thibela kholo ea B-cell lymphomas e hōlileng tsebong, ho akarelletsa le myeloma e mengata, 'me e etsa hore IL-2 e lokolloe liseleng tsa T.

Ka morao

Lenalidomide (e tsejoang hape e le CC-5013), e nkiloeng ka molomo ho thalidomide, ke moemeli oa antitumor e bonts'ang ts'ebetso ea antitumor ka mekhoa e fapaneng, ho kenyelletsa ts'ebetso ea sesole sa 'mele, thibelo ea angiogenesis, le litlamorao tse tobileng tsa antineoplastic. E 'nile ea ithutoa ka mokhoa o pharaletseng bakeng sa phekolo ea lefu la myeloma le myelodysplastic hammoho le mafu a lymphoproliferative ho akarelletsa le chronic lymphocytic leukemia (CLL) le non-Hodgkin lymphoma. Ho ea ka lithuto tsa morao-rao, Lnalidomide e khothalletsa le ho tsosolosa tsamaiso ea 'mele ea ho itšireletsa mafung ho bakuli ba CLL ka ho susumetsa maikutlo a feteletseng a limolek'hule tsa costimulatory ho leukemic lymphocyte ho tsosolosa ts'oaetso ea humoral le tlhahiso ea li-immunoglobulins hammoho le ho ntlafatsa bokhoni ba lisele tsa T le lisele tsa leukemic ho theha synapses le T. li-lymphocyte.

Referense

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

Ka Vitro

Lenalidomide e na le matla a ho susumetsa ho ata ha T cell le IFN-γ le tlhahiso ea IL-2. Lenalidomide e bontšitsoe ho thibela tlhahiso ea pro inflammatory cytokines TNF-α, IL-1, IL-6, IL-12 le ho phahamisa tlhahiso ea anti-inflammatory cytokine IL-10 ho tloha ho PBMC ea batho. Lenalidomide e fokotsa tlhahiso ea IL-6 ka ho toba hape ka ho thibela lisele tse ngata tsa myeloma (MM) le tšebelisano ea lisele tsa masapo a stromal (BMSC), e leng ho eketsang apoptosis ea lisele tsa myeloma[2]. Tšebelisano e itšetlehileng ka tekanyo ea litekanyetso le motsoako oa CRBN-DDB1 e bonoa ka Thalidomide, Lenalidomide le Pomalidomide, e nang le litekanyetso tsa IC50 tsa ~ 30.μM, ~3μM le ~3μM, ka ho latellana, Lisele tsena tse fokolitsoeng tsa CRBN (U266-CRBN60 le U266-CRBN75) ha li arabele hantle ho feta lisele tsa batsoali ho liphello tsa antiproliferative Lenalidomide ho pholletsa le mefuta e fapaneng ea karabelo ea 0.01 ho ea ho 10μM[3]. Lenalidomide, analoge ea thalidomide, e sebetsa e le sekhomaretsi sa molek'hule lipakeng tsa motho E3 ubiquitin ligase cereblon le CKI.α e bontšoa ho etsa hore ho be le hohle le ho senyeha ha kinase ena, kahoo mohlomong ho bolaea lisele tsa leukemic ka ts'ebetso ea p53.

Chefo ea litekanyetso tsa Lenalidomide ho fihla ho 15, 22.5, le 45 mg/kg ka IV, IP, le PO litsela tsa tsamaiso. E lekanyelitsoe ke ho qhibiliha koloing ea rona ea litekanyetso tsa PBS, litekanyetso tsena tse phahameng tse ka finyelloang tsa Lenalidomide li mamelloa hantle ntle le lefu le le leng la toeba (lipalopalong tse 'nè tse fetisitsoeng) ho tekanyo ea 15 mg/kg IV. Habohlokoa, ha ho chefo e 'ngoe e bonoang thutong ea IV ea litekanyetso tsa 15 mg/kg (n=3) kapa 10 mg/kg (n=45) kapa boemong bofe kapa bofe bo bong ka litsela tsa IV, IP, le PO.

Polokelo

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