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Pomalidomide

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Chemical Structure| 19171-19-8 同义名 : CC-4047;3-amino Thalidomide;Pomalidomide. Brand name: Pomalyst.
CAS号 : 19171-19-8
货号 : A203253
分子式 : C13H11N3O4
纯度 : 98%
分子量 : 273.24
MDL号 : MFCD12756407
存储条件：

粉末 Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(182.99 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

2% DMSO+30% PEG 300+2% Tween 80+water 3 mg/mL

生物活性
靶点

  • TNF-α

    TNF-α, IC50:13 nM

  • CRBN
描述 Cereblon, encoded by CRBN gene, is the substrate recognition component of a DCX (DDB1-CUL4-X-box) E3 protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Cereblon, or the E3 ligase complex mediated normal degradation of key regulatory proteins is required for multiple biological processes, such as normal limb outgrowth. It is well reported that binding of thalidomide-related drugs, such as Lenalidomide, changes the substrate specificity of the E3 ligase complex, leading to decreased degradation of MEIS2 and other target proteins and increased degradation of MYC, IRF4, IKZF1 and IKZF3[5]. Pomalidomide is an analogue of thalidomide. The cellular target of pomalidomide is cereblon. In a fluorescence thermal melt assay utilizing recombinant CRBN (cereblon), it was revealed that pomalidomide bound to cereblon[6]. Pomalidomide increased HbF production in human erythroid cells at the concentration of 1 μM. After incubation for 6 days, pomalidomide induced 2-fold upregulation of γ-globin mRNA levels while decreased β-globin levels 2-fold, also at the concentration of 1 μM[7]. According to another report, pomalidomide was used at the concentrations between 1 nM and 10 μM in both CD4+ and CD8+ cells, pomalidomide significantly elevated IL-2, IL-5, IL-10, and IFN-γSchafer PH, Gandhi AK, Loveland MA, Chen RS, Man HW, Schnetkamp PP, Wolbring G, Govinda S, Corral LG, Payvandi F, Muller GW, Stirling DI. Enhancement of cytokine production and AP-1 transcriptional activity in T cells by thalidomide-related immunomodulatory drugs. J Pharmacol Exp Ther. 2003 Jun;305(3):1222-32. doi: 10.1124/jpet.102.048496. Epub 2003 Mar 20. PMID: 12649301.|. 8 doses of pomalidomide i.p. administrated at the dose of 0.5 mg/kg among a period of 19 days significantly enhanced the antitumor activity of rituximab in a disseminated lymphoma-bearing SCID mice xenograft model established by i.v. injection of Raji cells. The median survival time of animals treated with pomalidomide and rituximab was 74 days compared to 38 days of those treated with rituximab monotherapy, while pomalidomide was not effective as a single agent[8].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
APK-1 39-1250 nM Growth Inhibition Assay 5 d IC50=226 nM, inhibits cell viability dose dependently 26119939
BC-1 39-1250 nM Growth Inhibition Assay 5 d IC50=744 nM, inhibits cell viability dose dependently 26119939
BC-3 39-1250 nM Growth Inhibition Assay 5 d IC50=107 nM, inhibits cell IC50=107 nM, viability dose dependently 26119939
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT01745640 Multiple Myeloma Phase 2 Completed - France ... 展开 >> CHRU-Hôpital Sud Amiens Amiens, France, 80054 Chru Caen Caen, France, 14033 CHU DIJON, Hôpital d'Enfants Dijon, France, 21000 CHRU, Hôpital A.Michallon Grenoble, France, 38043 Centre hospitalier départemental La Roche sur Yon La Roche sur Yon, France, 85025 Chru Lille Lille, France, 59037 Institut Paoli Calmette, Marseille, France, 13273 CHRU, Hôtel Dieu Nantes, France, 44035 Hôpital Saint-Louis Paris, France, 75475 CHU - Hôpital St Antoine, Paris, France, 75571 Hôpital Haut-Leveque PESSAC cedex, France, 33604 Centre Hospitalier Lyon Sud -1 Pierre Benite, France, 69495 Centre Hospitalier Lyon Sud -2 Pierre Benite, France, 69495 CHRU POITIERS-Hôpital Jean Bernard Poitiers, France, 86021 Hôpital Robert Debré, CHU Reims Reims, France, 51092 CHRU RENNES 2, Hôpital Pontchaillou Rennes, France, 35033 CHRU RENNES 1, Hôpital Sud Rennes, France, 35056 CHRU, Hôpital Purpan Toulouse, France, 31059 CHRU- Hôpital Bretonneau Tours, France, 37044 CHRU, Hôpitaux de Brabois Vandoeuvre, France, 54511 收起 <<
NCT03227432 Multiple Myeloma Phase 2 Withdrawn(Withdrawn before enr... 展开 >>ollment due to issues around the FDA hold on PD-1/PD-L1 drugs in combination with IMIDs.) 收起 << December 31, 2024 United States, Massachusetts ... 展开 >> Massachusetts General Hospital Boston, Massachusetts, United States, 02114 Beth Israel Deaconess Medical Center Boston, Massachusetts, United States, 02115 Dana Farber Cancer Institute Boston, Massachusetts, United States, 02115 收起 <<
NCT02654132 Multiple Myeloma Phase 2 Active, not recruiting April 22, 2019 -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.66mL

0.73mL

0.37mL

18.30mL

3.66mL

1.83mL

36.60mL

7.32mL

3.66mL
参考文献

[1]Li Z, Qiu Y, et al. Pomalidomide shows significant therapeutic activity against CNS lymphoma with a major impact on the tumor microenvironment in murine models. PLoS One. 2013 Aug 5;8(8):e71754.

[2]Ocio EM, Fernández-Lázaro D, et al. In vivo murine model of acquired resistance in myeloma reveals differential mechanisms for lenalidomide and pomalidomide in combination with dexamethasone. Leukemia. 2015 Mar;29(3):705-14.

[3]Lu G, Middleton RE, Sun H, Naniong M, Ott CJ, Mitsiades CS, Wong KK, Bradner JE, Kaelin WG Jr. The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins. Science. 2014 Jan 17;343(6168):305-9. doi: 10.1126/science.1244917. Epub 2013 Nov 29. PMID: 24292623; PMCID: PMC4070318.

[4]Lopez-Girona A, Mendy D, Ito T, Miller K, Gandhi AK, Kang J, Karasawa S, Carmel G, Jackson P, Abbasian M, Mahmoudi A, Cathers B, Rychak E, Gaidarova S, Chen R, Schafer PH, Handa H, Daniel TO, Evans JF, Chopra R. Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide. Leukemia. 2012 Nov;26(11):2326-35. doi: 10.1038/leu.2012.119. Epub 2012 May 3. Erratum in: Leukemia. 2012 Nov;26(11):2445. PMID: 22552008; PMCID: PMC3496085.

[5]Moutouh-de Parseval LA, Verhelle D, Glezer E, Jensen-Pergakes K, Ferguson GD, Corral LG, Morris CL, Muller G, Brady H, Chan K. Pomalidomide and lenalidomide regulate erythropoiesis and fetal hemoglobin production in human CD34+ cells. J Clin Invest. 2008 Jan;118(1):248-58. doi: 10.1172/JCI32322. PMID: 18064299; PMCID: PMC2117764.

[6]Hernandez-Ilizaliturri FJ, Reddy N, Holkova B, Ottman E, Czuczman MS. Immunomodulatory drug CC-5013 or CC-4047 and rituximab enhance antitumor activity in a severe combined immunodeficient mouse lymphoma model. Clin Cancer Res. 2005 Aug 15;11(16):5984-92. doi: 10.1158/1078-0432.CCR-05-0577. PMID: 16115943.