资料参考

IC50 Value: 13 nM [1] Lenalidomideis a derivative of thalidomide introduced in 2004. Lenalidomide (Revlimid, CC-5013) is a TNF-α secretion inhibitor with IC50 of 13 nM. in vitro: Lenalidomide strongly induces IL-2 and sIL-2R production. Lenalidomide-induced tyrosine phosphorylation of CD28 on T cells is followed by a down-stream activation of NF-κB [2]. Lenalidomide and pomalidomide inhibits autoubiquitination of CRBN in HEK293 T cells expressing thalidomide-binding competent wild-type CRBN, but not thalidomide-binding defective CRBN (YW/AA). Overexpression of CRBN wild-type protein, but not CRBN (YW/AA) mutant protein, in KMS12 myeloma cells, amplifies pomalidomide-mediated reductions in c-myc and IRF4 expression and increases in p21(WAF-1) expression. Long-term selection for Lenalidomide resistance in H929 myeloma cell lines is accompanied by a reduction in CRBN, while in DF15R myeloma cells resistant to both pomalidomide and Lenalidomide, CRBN protein is undetectable [3]. in vivo: Pharmacokinetic studies evaluated doses of 0.5, 1.5, 5, and 10 mg/kg IV and 0.5 and 10 mg/kg doses for IP and oral routes. Liquid chromatography-tandem mass spectrometry was used to quantify lenalidomide in plasma, brain, lung, liver, heart, kidney, spleen, and muscle [4]. Treatment with either thalidomide or lenalidomide attenuated weight loss, enhanced motor performance, decreased motor neuron cell death, and significantly increased the life span in G93A transgenic mice [5]. Toxicity: International Staging System III received a combination therapy of lenalidomide (15 mg, Day 1 - 21) with dexamethasone (40 mg, Day 1, 8, 15, 22). After 4 days on chemotherapy, he experienced worsened dyspnea and was urgently hospitalized because of acute respiratory failure [6]. Clinical trial: Lenalidomide As Immune Adjuvant In Patient's With Chronic Lymphocytic Leukemia (CLL). Phase 2