E3 Ligase; TNF-alpha

沙利度胺必须由肝脏代谢形成环氧化物，环氧化物可能是活性致畸代谢物。 [1]在培养物中用脂多糖和其他激动剂激活的人单核细胞会产生肿瘤坏死因子 α (TNF-α)，沙利度胺可特异性抑制该因子。 [2]沙利度胺增加 mRNA 降解，抑制肿瘤坏死因子 α 的产生。[3]沙利度胺通过诱导细胞凋亡或 G1 期生长停滞，直接影响对美法仑、阿霉素和地塞米松 (Dex) 耐药的 MM 细胞系和患者 MM 细胞。沙利度胺可增加 Dex 的抗 MM 活性，该活性可被白细胞介素 6 抑制。[4]沙利度胺是体外原代人类 T 细胞的有效共刺激剂。当与 T 细胞受体复合物的刺激相结合时，它通过白细胞介素 2 促进 T 细胞增殖并产生干扰素 γ。在缺乏 CD4+ T 细胞的情况下，沙利度胺还可以增强同种异体树突状细胞引起的初级 CD8+ 细胞毒性 T 细胞反应。 [5]

在三项实验中，沙利度胺（200 mg/kg）使家兔角膜血管数量减少了 30% 至 51%，中位减少量为 36%。 [1]

THP-1 细胞、A549 细胞和 KYSE30 细胞在添加有 10% 胎牛血清的 RPMI-1640 培养基中培养，并在 5% CO2 和 95% 室内空气环境中于 37°C 保存。使用单剂量4 Gy 6-MV X射线照射THP-1细胞，然后用或不用含有沙利度胺0.2μmol/mL的培养基处理细胞48小时。根据初步结果[2]，选择沙利度胺的浓度。

Mice: For the experiments, a total of 24 WT C57BL/6 mice are divided into 4 groups (n = 6 in each group): a control group, an irradiated group, an irradiated group plus Thalidomide, and a Thalidomide only group. The experiment uses 100 mg/kg of Thalidomide based on the preliminary findings. In a DMSO vehicle, thalidomide is dissolved. Every other day starting on day 1 for six treatments, the treatment group is gavaged with the recommended dose of thalidomide in 200 μL. 200 μL of 0.1% DMSO-containing saline is all that is given to the control mice. For the analysis, the lungs are removed 12 weeks after the radiation treatment. For the experiments, a total of 20 Nrf2-/- mice are divided into 4 groups at random (n = 5 per group). The same as with WT C57BL/6 mice, Nrf2-/- mice undergo the same experimental procedures. For the following experiments, 30 WT C57BL/6 mice are additionally randomly assigned to 5 groups (n = 6 in each group): a control group, an irradiated group, a group irradiated along with CDDO-Me and Thalidomide, a group irradiated along with CDDO-Me, and a group irradiated along with Thalidomide. The experimental CDDO-Me and Thalidomide doses are chosen to be 600 ng and 100 mg/kg, respectively. Every other day starting on day 1, for a total of six times, the treatment group is gavaged with the recommended dose of CDDO-Me or thalidomide in 200 μL. For the combined group receiving CDDO-Me and thalidomide, 200 L of CDDO-Me is administered by gavage every other day starting on day 1 for six treatments. Every other day starting on day 2 for six treatments, thalidomide is administered by gavage in 200 μL .

[1]. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):4082-5.

[2]. J Exp Med . 1991 Mar 1;173(3):699-703.

[3]. J Exp Med . 1993 Jun 1;177(6):1675-80.

[4]. Blood . 2000 Nov 1;96(9):2943-50.

[5]. J Exp Med . 1998 Jun 1;187(11):1885-92.

[6]. Nature . 2014 Aug 7;512(7512):49-53.

C13H10N2O4

258.23

258.06406

C, 60.47; H, 3.90; N, 10.85; O, 24.78

50-35-1

(S)-Thalidomide;841-67-8;Thalidomide-d4;1219177-18-0;(R)-Thalidomide;2614-06-4

Solid powder

C1CC(=O)NC(=O)C1N2C(=O)C3=CC=CC=C3C2=O

UEJJHQNACJXSKW-UHFFFAOYSA-N

InChI=1S/C13H10N2O4/c16-10-6-5-9(11(17)14-10)15-12(18)7-3-1-2-4-8(7)13(15)19/h1-4,9H,5-6H2,(H,14,16,17)

2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione

Nphthaloylglutamimide; alphaphthalimidoglutarimide; Nphthalylglutamic acid imide; US brand names: Synovir; Thalomid; Foreign brand names: Distaval; Contergan; Kevadon; Neurosedyn; Pantosediv; Softenon Talimol; Sedoval K17; Abbreviation: THAL

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.68 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (9.68 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 3: 30% PEG400+0.5% Tween80+5% Propylene glycol : 5 mg/mL

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Solubility in Formulation 4: 20 mg/mL (77.45 mM) in 0.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 5: 20 mg/mL (77.45 mM) in 10% Tween80 in PBS (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。