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ʻO Lenalidomide (CC-5013) he mea ia o Thalidomide a he immunomodulator hoʻoikaika waha. ʻO Lenalidomide (CC-5013) he ligand o ka ubiquitin E3 ligase cereblon (CRBN), a ke kumu ia i ka ubiquitination koho a me ka hoʻohaʻahaʻa ʻana o nā mea transcription lymphoid ʻelua, IKZF1 a me IKZF3, e ka CRBN-CRL4 ubiquitin ligase. ʻO Lenalidomide (CC-5013) ke kāohi pono i ka ulu ʻana o nā lymphomas B-cell makua, me ka myeloma lehulehu, a hoʻoulu i ka hoʻokuʻu ʻana o IL-2 mai nā pūnaewele T.

Kāpae

ʻO Lenalidomide (ʻike pū ʻia ʻo CC-5013), he ʻano oral derivative o thalidomide, he antineoplastic agent e hōʻike ana i ka hana antitumor ma o nā ʻano hana like ʻole, me ka hoʻoulu ʻana o ka ʻōnaehana pale, ka inhibition angiogenesis, a me nā hopena antineoplastic pololei. Ua aʻo nui ʻia no ka mālama ʻana i ka myeloma lehulehu a me ka myelodysplastic syndrome a me nā maʻi lymphoproliferative me ka maʻi lymphocytic maʻi (CLL) a me ka lymphoma non-Hodgkin. Wahi a nā noiʻi hou loa, hoʻolalelale a hoʻihoʻi ʻo Lnalidomide i ka hana ʻōnaehana immune i nā maʻi maʻi CLL ma o ka hoʻoulu ʻana i ka overexpression o nā molekala costimulatory i nā lymphocytes leukemic e hoʻihoʻi i ka hoʻomaʻamaʻa humoral a me ka hana immunoglobulins a me ka hoʻomaikaʻi ʻana i ka hiki o nā cell T a me nā cell leukemic e hana i nā synapses me T lymphocytes.

Kuhikuhi

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

In Vitro

He ikaika ka Lenalidomide i ka hoʻoulu ʻana i ka hoʻonui ʻana o ka cell T a me IFN-γ a me ka hana IL-2. Ua hōʻike ʻia ʻo Lenalidomide e kāohi i ka hana ʻana o nā cytokine pro inflammatory TNF-α, IL-1, IL-6, IL-12 a hoʻokiʻekiʻe i ka hana o ka cytokine anti-inflammatory IL-10 mai nā PBMC kanaka. Hoʻohaʻahaʻa ʻo Lenalidomide i ka hana ʻana o ka IL-6 a me ke kāohi ʻana i nā cell myeloma (MM) lehulehu a me ka pilina o ka iwi marrow stromal cell (BMSC), e hoʻonui ana i ka apoptosis o nā cell myeloma [2]. ʻIke ʻia ka pilina pili ʻana me ka CRBN-DDB1 complex me Thalidomide, Lenalidomide a me Pomalidomide, me nā waiwai IC50 o ~30μM, ~3μM a me ~3μM, kēlā me kēia, ʻO kēia mau mea hōʻike hōʻike CRBN i hoʻemi ʻia (U266-CRBN60 a me U266-CRBN75) ʻoi aku ka liʻiliʻi o ka pane ʻana ma mua o nā cell makua i nā hopena antiproliferative Lenalidomide ma waena o kahi pae pane-pane o 0.01 a 10.μM[3]. ʻO Lenalidomide, kahi analog thalidomide, hana ma ke ʻano he molecular glue ma waena o ke kanaka E3 ubiquitin ligase cereblon a me CKIα hōʻike ʻia e hoʻoulu i ka ubiquitination a me ka hoʻohaʻahaʻa ʻana o kēia kinase, no laila ke pepehi ʻia nei nā cell leukemic e ka p53 activation.

ʻO ka ʻawaʻawa o Lenalidomide a hiki i ka 15, 22.5, a me 45 mg/kg ma o nā ala IV, IP, a me PO o ka hoʻokele. Hoʻopaʻa ʻia e ka solubility i kā mākou PBS dosing kaʻa, ʻae maikaʻi ʻia kēia mau kikoʻī Lenalidomide kiʻekiʻe loa me ka ʻae ʻana o hoʻokahi make ʻiole (o ʻehā ka nui o ka dosed) ma ka 15 mg/kg IV. ʻO ka mea nui, ʻaʻohe mea ʻona ʻē aʻe i ʻike ʻia ma ke aʻo ʻana ma nā dosis IV o 15 mg/kg (n=3) a i ʻole 10 mg/kg (n=45) a i ʻole ma kekahi pae hoʻohālikelike ʻē aʻe ma o nā ala IV, IP, a me PO.

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