Emapticap pegol

镜像异构体是类似 RNA 的分子，可以结合蛋白质和肽等物质。它们由 L-核糖单元构成。人类特有的 CCL2 镜像异构体称为 NOX-E36，而小鼠特有的 CCL2 镜像异构体称为 mNOX-E36[2]。当人类单核细胞白血病细胞系 THP-1 暴露于 1 nM NOX-E36 时，会显着抑制 CCL2 介导的迁移 [2]。 NOX-E36 可阻止 MCP-1 介导的炎症细胞募集和巨噬细胞发育，并抑制单核细胞趋化蛋白-1 (MCP-1) [3]。 mNOX-E36 以剂量依赖性方式（约为正常迁移的 2000 倍）抑制小鼠造血细胞的迁移和信号通路激活以及表达 CCL2 受体的 Ba/F3 细胞 (Ba/F3-CCR2) 的迁移[2]。在 mCCL2 刺激的细胞中（30 分钟），mNOX-E36 分别消除 CCL2 诱导的 AKT、ERK 和 p35-MAPK 磷酸化 [2]。

Emapticap pegol（14.4 mg/kg，mNOX-E36；皮下注射；每周 3 次，持续 3 周）干扰 M2 样巨噬细胞浸润到白血病小鼠的脾脏中 [2]。 Emapticap pegol（20 mg/kg，mNOX-E36；皮下注射；每周 3 次，持续 4 周）可减少糖尿病小鼠的蛋白尿并恢复肾小球内皮糖萼 [3]。

Animal/Disease Models: Unirradiated immunocompetent C57BL/6 mice injected with syngeneic AML1/ETO9a-expressing primary mouse leukemia cells [2]
Doses: 14.4 mg/kg (mNOX-E36, mouse-specific CCL2 Spiegelmer's Emapticap pegol)
Route of Administration: subcutaneous injection; 3 times a week for 3 weeks
Experimental Results: Elimination of macrophage infiltration in the leukemia microenvironment.

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Animal/Disease Models: Diabetic male Apoe KO C57BL/6J mice (6 weeks old) [3]
Doses: 20 mg/kg (mNOX-E36, mouse-specific CCL2 Spiegelmer’s Emapticap pegol)
Route of Administration: subcutaneous injection ; 3 times a week for 4 weeks.
Experimental Results: The albumin/creatinine ratio was diminished, but the blood sugar level and weight of the mice were not affected. Heparanase and cathepsin L expression was diminished.

[1]. C-C motif-ligand 2 inhibition with emapticap pegol (NOX-E36) in type 2 diabetic patients with albuminuria. Nephrol Dial Transplant. 2017 Feb 1;32(2):307-315.

[2]. Effects of CCL2/CCR2 Blockade in Acute Myeloid Leukemia. Blood.

[3]. Systemic Monocyte Chemotactic Protein-1 Inhibition Modifies Renal Macrophages and Restores Glomerular Endothelial Glycocalyx and Barrier Function in Diabetic Nephropathy. Am J Pathol. 2017 Nov;187(11):2430-2440.

Olaptesed Pegol has been investigated for the treatment of Hematopoietic Stem Cell Transplantation.
Lexaptepid pegol has been used in trials studying the treatment of Anemia, Inflammation, Chronic Diseases, End Stage Renal Disease, and Anemia of Chronic Disease.
Lexaptepid Pegol is a proprietary 44-nucleotide L-stereoisomer RNA oligonucleotide conjugated to a 40 kDa polyethylene glycol (PEG) that targets hepcidin with potential anti-anemic activity. Upon intravenous or subcutaneous administration, lexaptepid pegol binds to hepcidin and prevents it from binding to the iron channel ferroportin, located on the basolateral surface of gastrointestinal enterocytes and the plasma membrane of macrophages. This prevents hepcidin-induced internalization and degradation of ferroportin, thus decreasing macrophage iron retention. In turn, binding of NOX-H94 to hepcidin normalizes plasma iron levels and increases erythropoiesis. This may inhibit anemia caused by inflammation. Hepcidin, a peptide hormone that plays a key role in the homeostasis of systemic iron, is upregulated during acute and chronic inflammation in response to cytokines. The unique mirror-image configuration of this agent renders it resistant to hydrolysis and shows a low antigenicity profile. Pegylation increases the half-life of this agent.
Olaptesed Pegol is a 45-mer L-stereoisomer RNA oligonucleotide linked to a 40 kDa polyethyleneglycol that targets the small chemokine stromal cell-derived factor 1 (SDF-1 or CXCL12) with potential antineoplastic and hematopoietic stem cell-mobilization activities. SDF-1 targeted agent NOX-A12 specifically binds to SDF-1 thereby preventing the binding of SDF-1 to its receptors CXCR4 and CXCR7 blocking the subsequent receptor activation. This may prevent angiogenesis, tumor cell proliferation, invasion and metastasis and could sensitize tumor cells to chemotherapy. In addition, inhibition of SDF-1/CXCR4 interaction may induce mobilization of hematopoietic cells from the bone marrow into blood. The unique mirror-image configuration of this agent renders it resistant to hydrolysis and does not hybridize with native nucleic acids. Furthermore, this agent does not induce the innate immune response and has shown a favorable immunogenicity profile.

C18H37N2O10P

472.467547178268

472.218

1390630-22-4

86278354

Typically exists as solid at room temperature

-1.8

153

3

10

21

31

518

0

QJAGBAPUFWBVSD-UHFFFAOYSA-N

InChI=1S/C18H37N2O10P/c1-26-11-13-28-10-8-20(18(22)16-29-14-12-27-2)15-17(21)19-7-5-3-4-6-9-30-31(23,24)25/h3-16H2,1-2H3,(H,19,21)(H2,23,24,25)

6-[[2-[[2-(2-methoxyethoxy)acetyl]-[2-(2-methoxyethoxy)ethyl]amino]acetyl]amino]hexyl dihydrogen phosphate

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)

H2O : ~50 mg/mL

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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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。