来那度胺半水合物 T22922

Product Introduction
Bioactivity


英文名: Lenalidomide hemihydrate

描述: Lenalidomide hemihydrate 是 Thalidomide 的衍生物，也是具有口服活性免疫调节剂，以分子胶的方式作用。它是泛素 E3 连接酶 cereblon 的配体，通过 CRBN-CRL4 泛素连接酶对两种淋巴转录因子 IKZF1 和 IKZF3 进行选择性泛素化和降解。

体外活性: Lenalidomide inhibited autoubiquitination of CRBN in HEK293T 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, amplified 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 was accompanied by a reduction in CRBN, while in DF15R myeloma cells resistant to lenalidomide, CRBN protein was undetectable[1].

体内活性: Range finding studies used lenalidomide concentrations up to 15 mg/kg IV, 22.5 mg/kg intraperitoneal injections (IP), and 45 mg/kg oral gavage (PO). 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. Pharmacokinetic parameters were estimated using noncompartmental and compartmental methods. Doses of 15 mg/kg IV, 22.5 mg/kg IP, and 45 mg/kg PO lenalidomide caused no observable toxicity up to 24 h postdose. We observed dose-dependent kinetics over the evaluated dosing range. Administration of 0.5 and 10 mg/kg resulted in systemic bioavailability ranges of 90-105% and 60-75% via IP and oral routes, respectively. Lenalidomide was detectable in the brain only after IV dosing of 5 and 10 mg/kg. Dose-dependent distribution was also observed in some tissues. High oral bioavailability of lenalidomide in mice is consistent with oral bioavailability in humans. Atypical lenalidomide tissue distribution was observed in spleen and brain[3].

存储条件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度: DMSO : Soluble


关键字: IKZF3 | inhibit | IKZF1 | ligand | Inhibitor | CC-5013 hemihydrate | degradation | myeloma | Lenalidomide Hemihydrate | Ligands for E3 Ligase | analog | multiple | Lenalidomide hemihydrate | Lenalidomide | immunomodulatory | E3 ligase-recruiting Moiety | CRL4 | ligase | Molecular Glues | cereblon | Apoptosis

相关产品: XY028-140 | (S,R,S)-AHPC | TD-165 | (S,R,S)-AHPC-PEG4-NH2 | (S,R,S)-AHPC-C4-NH2 hydrochloride | CFT7455 | (S,R,S)-AHPC-C10-NH2 | dCBP-1 | Thalidomide-propargyl | Thalidomide-O-amido-PEG3-C2-NH2 TFA

相关库: Approved Drug Library | EMA Approved Drug Library

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