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Thalidomide

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Chemical Structure| 50-35-1 同义名 : (±)-沙利度胺 ;N-Phthaloylglutamimide;K17;Abbreviation: THAL.;Softenon Talimol;Sedoval K17;Pantosediv;Neurosedyn;Kevadon;Distaval;Thalomid. Foreign brand names: Contergan;Nphthalylglutamic acid imide. US brand names: Synovir;alphaphthalimidoglutarimide. Nphthaloylglutamimide;NSC 527179;NSC 66847;(±)-Thalidomide
CAS号 : 50-35-1
货号 : A164079
分子式 : C13H10N2O4
纯度 : 98%
分子量 : 258.229
MDL号 : MFCD00153873
存储条件：

粉末 Keep in dark place,Sealed in dry,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(406.62 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：

IP 2% DMSO+2% Tween80+40% PEG300+water 1.3 mg/mL clear

PO 0.5% CMC-Na 47 mg/mL suspension

生物活性
靶点

  • TNF-α

  • E3 Ligase
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{Krönke J, Udeshi ND, Narla A, Grauman P, Hurst SN, McConkey M, Svinkina T, Heckl D, Comer E, Li X, Ciarlo C, Hartman E, Munshi N, Schenone M, Schreiber SL, Carr SA, Ebert BL. Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science. 2014 Jan 17;343(6168):301-5. doi: 10.1126/science.1244851. Epub 2013 Nov 29. PMID: 24292625; PMCID: PMC4077049.|https://pubmed.ncbi.nlm.nih.gov/24292625/}}[6]. The cellular target of thalidomide is cereblon. In a fluorescence thermal melt assay utilizing recombinant CRBN (cereblon), it was revealed that thalidomide bound to cereblon[7]. According to a report, thalidomide dose-dependently increased the proliferative responses of PBMCs stimulated by immobilized anti-CD3, with obvious effects shown at the concentration of 10 μg/ml[8]. In a rabbit model of angiogenesis assay, corneal neovascularization was induced by implantation of pellets into corneal micropockets of eyes in anesthetized female New Zealand White rabbits. When given at the dose of 200 mg/kg p.o., thalidomide inhibited the area of vascularized cornea, with a median inhibition of 36%, and the inhibition of thalidomide on angiogenesis was seen after two doses[9]. In a human lung cancer xenograft model established in Balb/c nude mice by subcutaneous injection of PC9 cells, thalidomide was orally administrated at the dose of 200 mg/kg daily for 18 days. In this experiment the combination of thalidomide with icotinib was of significant anti-tumor activity[10].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
HeLa cells Function assay Inhibition of IL-1-alpha-induced NF-kappaB activation in HeLa cells assessed as blocking of p50/p65 nuclear translocation, IC50=2.04 μM 17845850
mouse RAW264.7 cells 10 μM Function assay 3 h Reduction in pERK1/2 expression in LPS-activated mouse RAW264.7 cells at 10 uM pretreated for 3 hrs before LPS challenge assessed after 24 hrs by Western blot 18723357
mouse RAW264.7 cells 10 μM Function assay Reduction in iNOS expression in LPS-activated mouse RAW264.7 cells at 10 uM pretreated for 3 hrs before LPS challenge assessed after 24 hrs by Western blot 18723357
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
NCT00287872 - Completed - -
NCT00287872 Multiple Myeloma Phase 2 Completed - United States, Maryland ... 展开 >> Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland, United States, 21231-2410 收起 <<
NCT00301405 Chronic Prostatitis ... 展开 >> Pelvic Pain 收起 << Phase 2 Terminated(Study closed. Diffi... 展开 >>cult enrollment of patients with prostatitis.) 收起 << - United States, Michigan ... 展开 >> William Beaumont Hospital Royal Oak, Michigan, United States, 48073 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.87mL

0.77mL

0.39mL

19.36mL

3.87mL

1.94mL

38.73mL

7.75mL

3.87mL
参考文献

[1]Fischer ES, Bohm K, et al. Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide. Nature. 2014 Aug 7;512(7512):49-53.

[2]D'Amato RJ, Loughnan MS, et al. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):4082-5.

[3]Schumacher H, Blake DA, et al. A comparison of the teratogenic activity of thalidomide in rabbits and rats. J Pharmacol Exp Ther. 1968 Mar;160(1):189-200.

[4]Lu J, Palmer BD, et al. Thalidomide metabolites in mice and patients with multiple myeloma. Clin Cancer Res. 2003 May;9(5):1680-8.

[5]Thalidomide

[6]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.

[7]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.

[8]Haslett PA, Corral LG, Albert M, Kaplan G. Thalidomide costimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+ subset. J Exp Med. 1998 Jun 1;187(11):1885-92. doi: 10.1084/jem.187.11.1885. PMID: 9607928; PMCID: PMC2212313.

[9]D'Amato RJ, Loughnan MS, Flynn E, Folkman J. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):4082-5. doi: 10.1073/pnas.91.9.4082. PMID: 7513432; PMCID: PMC43727.

[10]Sun X, Xu Y, Wang Y, Chen Q, Liu L, Bao Y. Synergistic Inhibition of Thalidomide and Icotinib on Human Non-Small Cell Lung Carcinomas Through ERK and AKT Signaling. Med Sci Monit. 2018 May 15;24:3193-3203. doi: 10.12659/MSM.909977. PMID: 29763936; PMCID: PMC5978026.