Sharaxaada

Lenalidomide (CC-5013) waa asal ka soo jeeda Thalidomide iyo immunomodulator afka ah oo firfircoon. Lenalidomide (CC-5013) waa ligand ka mid ah ubiquitin E3 ligase cereblon (CRBN), waxayna keentaa meelaynta xulashada iyo hoos u dhigista laba arrimood oo lymphoid ah, IKZF1 iyo IKZF3, by CRBN-CRL4 ubiquitin ligase. Lenalidomide (CC-5013) waxay si gaar ah u joojisaa koritaanka lymphomas B-cell, oo ay ku jiraan myeloma badan, waxayna keentaa in IL-2 laga sii daayo unugyada T.

Asalkii hore

Lenalidomide (oo sidoo kale loo yaqaan CC-5013), oo ka soo jeeda afka thalidomide, waa wakiilka antineoplastic oo soo bandhigaya waxqabadka antitumor iyada oo loo marayo habab kala duwan, oo ay ku jiraan firfircoonida habka difaaca jirka, xakamaynta angiogenesis, iyo saamaynta tooska ah ee antineoplastic. Waxaa si weyn loo bartay daaweynta myeloma badan iyo myelodysplastic syndrome iyo sidoo kale ciladaha lymphoproliferative oo ay ku jiraan lymphocytic leukemia (CLL) iyo lymphoma non-Hodgkin. Sida laga soo xigtay daraasadihii dhawaa, Lnalidomide wuxuu kor u qaadaa oo dib u soo celiyaa shaqada nidaamka difaaca ee bukaanada CLL iyadoo ay soo jiidanayso xad-dhaaf ah oo ah molecules costimulatory ee leukemic lymphocytes si loo soo celiyo difaaca humoral iyo wax soo saarka immunoglobulins iyo sidoo kale hagaajinta awoodda unugyada T iyo unugyada leukemic si ay u sameeyaan synapses leh T. lymphocytes.

Tixraac

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

In Vitro

Lenalidomide waxay awood u leedahay kicinta kororka unugyada T-ga iyo IFN-γ iyo IL-2 wax soo saarka. Lenalidomide ayaa lagu muujiyay in ay joojiso soo saarista cytokines pro bararka ee TNF-α, IL-1, IL-6, IL-12 iyo kor u qaadida wax soo saarka cytokine anti-bararka IL-10 ee PBMCs aadanaha. Lenalidomide waxay hoos u dhigtaa wax soo saarka IL-6 si toos ah iyo sidoo kale iyada oo la xakameynayo unugyo badan oo myeloma (MM) iyo unugyada dhuuxa lafaha (BMSC), taas oo kordhisa apoptosis ee unugyada myeloma [2]. Isdhexgalka qiyaasta-ku-tiirsanaanta ee isku-dhafka CRBN-DDB1 ayaa lagu arkay Thalidomide, Lenalidomide iyo Pomalidomide, oo leh IC50 qiimaha ~ 30μM, ~3μM iyo ~3μM, siday u kala horreeyaan, Unugyadan muujinta CRBN ee la dhimay (U266-CRBN60 iyo U266-CRBN75) way ka yar yihiin kuwa ka jawaab celinaya unugyada waalidka ee saamaynta antiproliferative Lenalidomide guud ahaan qiyaasta jawaabta qiyaasta ee 0.01 ilaa 10μM[3]. Lenalidomide, analooga thalidomide, wuxuu u shaqeeyaa sida xabagta molecular ee u dhaxaysa bini'aadamka E3 ubiquitin ligase cereblon iyo CKIα waxaa lagu muujiyay in uu keeno meel-ka-baxa iyo hoos u dhaca kinase-kan, sidaas awgeed waxay u badan tahay in ay dilaan unugyada leukemic by p53 activation.

Sunta qiyaasta Lenalidomide ilaa 15, 22.5, iyo 45 mg/kg iyada oo loo sii marayo IV, IP, iyo PO waddooyinka maamulka. Xaddidan milanka ee gaadhiga qiyaasta PBS, qiyaasahan ugu badan ee Lenalidomide ee la heli karo si fiican ayaa loogu dulqaadanayaa marka laga reebo hal dhimasho oo jiir ah (oo ah afar wadarta qiyaasta) ee 15 mg/kg IV qiyaasta. Waxaa xusid mudan, wax sun ah laguma arko daraasadda qiyaasta IV ee 15 mg/kg (n=3) ama 10 mg/kg (n=45) ama heer kasta oo kale oo qiyaas ah iyada oo loo marayo waddooyinka IV, IP, iyo PO.

Kaydinta

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Xogta Nafleyda ee La Xidhiidha

Xogta Nafleyda ee La Xidhiidha