1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemELenalidomideCat. No.: HY-A0003CAS No.: 191732-72-6Synonyms: CC-5013分式: CHNO分量: 259.26作靶點: Ligand for E3 Ligase作通路: PROTAC儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數據體外實驗 DMSO : 35 mg/mL (135.00 mM)

2、* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 3.8571 mL 19.2857 mL 38.5713 mL5 mM 0.7714 mL 3.8571 mL 7.7143 mL10 mM 0.3857 mL 1.9286 mL 3.8571 mL請根據產品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內實驗請根據您的實驗動物和給藥式選擇適當的溶解案，配制前請先配制澄的儲備液，再依次添加助溶劑(為保證實驗結果的可靠性，體內實驗的

3、作液，建議您現現配，當天使；澄的儲備液可以根據儲存條件，適當保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (8.02 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (8.02 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師ww

4、w.MedChemE3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.08 mg/mL (8.02 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Lenalidomide 與 E3 連接酶 cereblon 相互作，為連接酪蛋激酶 1A1 (CKI) 與 E3 連接酶 cereblon 的蛋質穩態調節劑，誘導 CKI 的降解。IC50 & Target Cereblon體外研究 Lenalidomide is potent in stimulating T cell proliferation and IFN

5、- and IL-2 production. Lenalidomide hasbeen shown to inhibit production of pro inflammatory cytokines TNF-, IL-1, IL-6, IL-12 and elevate theproduction of anti-inflammatory cytokine IL-10 from human PBMCs. Lenalidomide downregulates theproduction of IL-6 directly and also by inhibiting multiple myel

6、oma (MM) cells and bone marrow stromal cells(BMSC) interaction, which augments the apoptosis of myeloma cells 2. Dose-dependent interaction with theCRBN-DDB1 complex is observed with Thalidomide, Lenalidomide and Pomalidomide, with IC50 values of30 M, 3 M and 3 M, respectively, These reduced CRBN ex

7、pression cells (U266-CRBN60 and U266-CRBN75) are less responsive than the parental cells to antiproliferative effects Lenalidomide across a dose-response range of 0.01 to 10 M 3. Lenalidomide, a thalidomide analog, functions as a molecular gluebetween the human E3 ubiquitin ligase cereblon and CKI i

8、s shown to induce the ubiquitination anddegradation of this kinase, thus presumably killing leukemic cells by p53 activation 5.體內研究 The toxicity of Lenalidomide doses up to 15, 22.5, and 45 mg/kg via IV, IP, and PO routes of administration.Limited by solubility in our PBS dosing vehicle, these maxim

9、um achievable Lenalidomide doses are welltolerated with the exception of one mouse death (of four total dosed) at the 15 mg/kg IV dose. Notably, noother toxicities are observed in the study at IV doses of 15 mg/kg (n=3) or 10 mg/kg (n=45) or at any otherdose level through IV, IP, and PO routes 4.PRO

10、TOCOLCell Assay 3 Cell lines NCI-H929 and U266, and DF15 cells are grown in RPMI-I640 medium containing 10% (V/V) heat-inactivated fetal bovine serum supplemented with 2 mM glutamine. To produce Lenalidomide resistant celllines, NCI-H929 cells are treated continuously (fresh Lenalidomide is added ev

11、ery 3-4 days) with control(final 0.1% DMSO) or low-dose Lenalidomide (1 M) for 2 months until the proliferation of cells is no longerinhibited by Lenalidomide (1 M), as determined by cell viability (Vi-cell XR cell viability analyzer), cellproliferation by flow cytometry and cell cycle analysis (pro

12、pidium iodide staining). After acquisition ofresistance to 1 M, the resistant H929 cell lines are treated with Lenalidomide (10 M) for a further 4 months.After this period of time, the cell cultures achieved fully establish resistance up to high-dose Lenalidomide (30M). Prior to the experiments desc

13、ribed here, H929 Lenalidomide-resistant cells are taken out of culture withcompounds for 5-7 days before use 3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEAnimal Mice 4Administration 4 Imprinting cont

14、rol region (ICR) mice 8-10 weeks of age are used. Lenalidomide is incompletely soluble at 3.5mg/mL and above in PBS containing 1% HCl, as visible particulates remained after thorough mixing.Therefore 3 mg/mL is selected as the maximum dosing solution concentration (with no visible particulates).Sing

15、le, individual mice are initially dosed with 3, 10, or 15 mg/kg IV; 4.5, 15, or 22.5 mg/kg IP; and 9, 30, or45 mg/kg PO. Additional mice (n=4) are then evaluated at the maximum dose achievable by volume andsolubility of Lenalidomide in the dosing solution. All mice are monitored closely for 1 h and

16、re-evaluated fortoxicities 3, 6, and 24 h postdose 4.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產品發表的科研獻 Cell. 2018 Sep 20;175(1):171-185.e25. Nat Commun. 2017 May 22;8:15398. Cell Syst. 2018 Apr 25;6(4):424-443.e7. Elife. 2018 Aug 1;7. pii: e38

17、430. Food Chem Toxicol. 2019 Mar;125:392-402.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Omran A, et al. Effects of MRP8, LPS, and lenalidomide on the expressions of TNF- , brain-enriched, and inflammation-relatedmicroRNAs in the primary astrocyte culture. ScientificWorldJo

18、urnal. 2013 Sep 21;2013:208309.2. Kotla V, et al. Mechanism of action of lenalidomide in hematological malignancies. J Hematol Oncol. 2009 Aug 12;2:36.3. Lopez-Girona A, et al. Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide andpomalidomide. Leukemia. 2012 Nov;26(11):2326-35.4. Rozewski DM, et al. Pharmacokinetics and tissue dispositio