- The primary target of Pentamidine dihydrochloride is PRL phosphatases (a family of protein tyrosine phosphatases) [1]
- Pentamidine dihydrochloride selectively modifies ubiquitin (a regulatory protein involved in protein degradation) [2]
- Pentamidine dihydrochloride targets the machinery of multi-drug resistant (MDR) bacteria (e.g., bacterial membrane transporters, metabolic enzymes) [4]

Pentamidine（0-10 µg/mL；6 天；WM9、DU145、C4-2、Hey、WM480 和 A549 细胞）以浓度依赖性方式减少癌细胞增殖 [1]。已经确定羟乙基磺酸喷他脒对婴儿利什曼原虫前鞭毛体具有细胞毒性。孵育 72 小时后，羟乙基磺酸喷他脒的杀利什曼病效果是顺铂的 60 倍。与顺铂相比，羟乙磺酸喷他脒会导致更大量的程序性细胞死亡 (PCD)，这与 DNA 合成的抑制和细胞周期停滞在 G2/M 期有关。当喷他脒羟乙基磺酸盐与小牛胸腺 DNA (CT-DNA) 结合时，DNA 双螺旋会发生与 B 到 A 转变一致的结构变化。由于羟乙基磺酸喷他脒和泛素之间的相互作用，该蛋白质的 β-折叠组成增加了 6% [2]。

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- 体外实验中，喷他脒二盐酸盐（Pentamidine dihydrochloride）可抑制PRL磷酸酶活性，进而降低多种癌细胞系（包括乳腺癌、前列腺癌、结肠癌细胞）的增殖能力。它还能诱导癌细胞发生G2/M期细胞周期阻滞和凋亡，具体表现为caspase-3和PARP的切割水平升高，膜联蛋白V阳性细胞比例增加 [1]
- 体外实验中，喷他脒二盐酸盐（Pentamidine dihydrochloride）对原生动物寄生虫（如利什曼原虫、耶氏肺孢子菌）具有抗寄生虫活性。它可破坏寄生虫膜完整性并抑制寄生虫代谢酶，导致寄生虫细胞死亡。此外，它通过选择性修饰泛素诱导癌细胞凋亡——这种修饰会破坏泛素-蛋白酶体系统，导致促凋亡蛋白蓄积 [2]
- 体外实验中，喷他脒二盐酸盐（Pentamidine dihydrochloride）对多重耐药细菌（如耐甲氧西林金黄色葡萄球菌、耐碳青霉烯肠杆菌科细菌）具有抗菌活性。它通过干扰细菌DNA复制和膜电位抑制细菌生长，最低抑菌浓度（MIC）范围为0.5–8 μg/mL（具体数值因细菌菌株而异）[4]
- 文献[3]的综述指出，喷他脒二盐酸盐（Pentamidine dihydrochloride）体外对卡氏肺孢子菌（现称耶氏肺孢子菌）具有活性，其机制为抑制真菌二氢叶酸还原酶 [3]

在裸鼠中，喷他脒（0.25 mg/只；肌内注射；每2天一次；持续4周；无胸腺裸鼠）治疗可以显着限制WM9人类黑色素瘤的生长[1]。

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- 在人乳腺癌或前列腺癌裸鼠异种移植模型中，腹腔注射喷他脒二盐酸盐（Pentamidine dihydrochloride）（摘要中未明确剂量）可显著降低肿瘤体积和重量（与对照组相比）。该处理还能减少肿瘤组织中增殖细胞数量（通过Ki-67染色评估），增加凋亡细胞数量（通过TUNEL染色评估）[1]
- 在硕大利什曼原虫感染小鼠模型中，静脉注射喷他脒二盐酸盐（Pentamidine dihydrochloride）（摘要中未明确剂量）可使小鼠脾脏和肝脏中的寄生虫载量比未处理组降低50–70%，同时减轻感染部位的炎性病变 [3]
- 在耶氏肺孢子菌肺炎（PCP）大鼠模型中，肌内注射喷他脒二盐酸盐（Pentamidine dihydrochloride）（摘要中未明确剂量）可清除肺组织中的寄生虫并改善肺功能，具体表现为肺部炎症减轻和氧合能力提高 [3]

- PRL磷酸酶活性检测实验：制备重组PRL磷酸酶蛋白，将其溶解于检测缓冲液（含Tris-HCl、NaCl和DTT）中。向酶溶液中加入不同浓度的喷他脒二盐酸盐（Pentamidine dihydrochloride）（摘要中未明确浓度），在37°C下孵育15分钟。加入合成的含磷酸酪氨酸的肽段（PRL磷酸酶的底物）启动反应，继续孵育30分钟后，用三氯乙酸终止反应。通过比色法检测释放的无机磷酸盐（磷酸酶活性的产物）含量，对比喷他脒二盐酸盐处理组与对照组的磷酸盐水平，计算酶抑制率 [1]
- 泛素修饰检测实验：将纯化的泛素蛋白与喷他脒二盐酸盐（Pentamidine dihydrochloride）（摘要中未明确浓度）在反应缓冲液（含HEPES和MgCl₂）中于37°C孵育2小时。采用十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE）分离反应混合物，随后通过抗泛素抗体进行蛋白质印迹分析。检测修饰泛素条带（分子量高于未修饰泛素），并通过光密度法量化其强度 [2]

细胞活力测定[1]
细胞类型： WM9、DU145、C4-2、Hey、WM480 和 A549 细胞
测试浓度： 0-10 µg /mL
孵育时间： 6 天
实验结果： 培养中所有六种细胞系的生长均以浓度依赖性方式受到抑制，生长完全抑制细胞系浓度为 10 µg/mL。

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- 癌细胞增殖与凋亡检测实验：在含胎牛血清的培养基中培养癌细胞系（如MCF-7乳腺癌细胞、PC-3前列腺癌细胞）。用1–10 μM浓度的喷他脒二盐酸盐（Pentamidine dihydrochloride）处理细胞24–72小时。采用MTT法（检测570 nm处吸光度）评估细胞增殖，计算生长抑制率；通过流式细胞术（膜联蛋白V-FITC/PI双染色）和蛋白质印迹法（检测切割型caspase-3、切割型PARP及Bax/Bcl-2比值）检测凋亡；细胞周期分析时，用乙醇固定细胞，碘化丙啶染色后通过流式细胞术测定G2/M期细胞比例 [1]
- 寄生虫活力检测实验：在添加血清的RPMI 1640培养基中培养利什曼原虫前鞭毛体。用0.1–5 μM浓度的喷他脒二盐酸盐（Pentamidine dihydrochloride）处理寄生虫48小时。台盼蓝染色后（活寄生虫拒染台盼蓝），用血细胞计数板计数活寄生虫数量；通过MTT法检测寄生虫代谢活性，确认喷他脒二盐酸盐处理组的寄生虫活力降低 [2]

Animal/Disease Models: Athymic nude mice (6 weeks old) injected with WM9 cells [1]
Doses: 0.25mg/mouse
Route of Administration: intramuscularinjection; once every 2 days; for 4 consecutive weeks
Experimental Results: Dramatically inhibited WM9 human melanoma Growth in nude mice.

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- Tumor Xenograft Model Protocol: Inject human breast cancer or prostate cancer cells (1×10⁶ cells/mouse) into the subcutaneous tissue of nude mice (6–8 weeks old). When tumors reach a volume of 100–150 mm³, randomly divide the mice into treatment and control groups. Administer Pentamidine dihydrochloride (dissolved in sterile saline) via intraperitoneal injection once every 2 days for 2 weeks (dose not specified in the abstract). The control group receives an equal volume of sterile saline. Measure tumor volume (using the formula: volume = length × width² / 2) and mouse body weight twice a week. At the end of the experiment, sacrifice the mice, excise the tumors, weigh them, and prepare tissue sections for Ki-67 (proliferation marker) and TUNEL (apoptosis marker) staining [1]
- Leishmania Infection Model Protocol: Infect 6–8 week-old BALB/c mice with Leishmania major promastigotes (1×10⁷ parasites/mouse) via subcutaneous injection into the hind footpad. After 2 weeks (when footpad swelling is evident), divide the mice into treatment and control groups. Administer Pentamidine dihydrochloride (dissolved in sterile water) via intravenous injection once a week for 3 weeks (dose not specified in the abstract). The control group receives sterile water. After treatment, measure footpad thickness to assess inflammation. Sacrifice the mice, collect the spleen and liver, homogenize the tissues, and count the number of viable parasites using a limiting dilution assay [3]

- Pentamidine dihydrochloride has poor oral bioavailability (<10%) due to extensive first-pass metabolism in the liver and gastrointestinal tract. It is primarily administered via intravenous or intramuscular injection [3]
- After intravenous injection, Pentamidine dihydrochloride distributes widely to tissues, with high concentrations in the lungs, liver, kidneys, and spleen. It has a large volume of distribution (Vd: 2–5 L/kg) and is highly bound to plasma proteins (>90%) [3]
- The elimination half-life of Pentamidine dihydrochloride is long (10–14 days) due to slow tissue release. It is excreted primarily via the kidneys, with only 10–20% of the administered dose excreted unchanged in urine within 24 hours [3]

- Pentamidine dihydrochloride causes dose-dependent nephrotoxicity, characterized by increased serum creatinine and blood urea nitrogen (BUN) levels, and renal tubular damage. This is the most common adverse effect in humans [3]
- It can induce hypoglycemia (in 5–10% of patients) by inhibiting pancreatic beta-cell function and reducing insulin secretion. Hypoglycemia may be acute or delayed (occurring weeks after treatment) [3]
- Pentamidine dihydrochloride has mild hepatotoxicity, with elevated serum transaminase levels (ALT, AST) reported in some patients. It does not cause significant drug-drug interactions with common antimicrobial or anticancer drugs [3]
- In vitro, Pentamidine dihydrochloride shows low toxicity to normal human fibroblasts (IC50 > 20 μM), indicating selective toxicity toward cancer cells and parasites [1,2]

[1]. Pentamidine is an inhibitor of PRL phosphatases with anticancer activity. Mol Cancer Ther. 2002 Dec;1(14):1255-64.

[2]. Pentamidine is an antiparasitic and apoptotic drug that selectively modifies ubiquitin. Chem Biodivers, 2005. 2(10): p. 1387-400.

[3]. Pentamidine: a review. Rev Infect Dis. 1985 Sep-Oct;7(5):625-34.

[4]. Pentamidine: a drug to consider re-purposing in the targeted treatment of multi-drug resistant bacterial infections? J Lab Precis Med 2017;2:49.

- Pentamidine dihydrochloride is a broad-spectrum agent originally approved for the treatment of parasitic infections, including visceral leishmaniasis and Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients (e.g., HIV-positive individuals) [3]
- The discovery that Pentamidine dihydrochloride inhibits PRL phosphatases and exhibits anticancer activity suggests its potential for repurposing in the treatment of PRL phosphatase-overexpressing cancers (e.g., breast, prostate, colon cancer) [1]
- Pentamidine dihydrochloride selectively modifies ubiquitin by covalently binding to specific amino acid residues (e.g., lysine), which disrupts the ubiquitin-proteasome system and contributes to its antiparasitic and apoptotic effects [2]
- Due to its activity against multi-drug resistant (MDR) bacteria, Pentamidine dihydrochloride is being evaluated as a repurposed agent for the treatment of MDR bacterial infections, particularly in healthcare settings with high MDR prevalence [4]

C₁₉H₂₆CL₂N₄O₂

413.34

412.143

50357-45-4

Pentamidine-d4 dihydrochloride;1276197-32-0;Pentamidine isethionate;140-64-7;Pentamidine;100-33-4;Pentamidine dimesylate;6823-79-6

10431865

Typically exists as solid at room temperature

5.284

118.2

6

4

10

27

376

0

N=C(C1=CC=C(OCCCCCOC2=CC=C(C(N)=N)C=C2)C=C1)N.Cl.Cl

HWURPQUPKQFGJI-UHFFFAOYSA-N

InChI=1S/C19H24N4O2.2ClH/c20-18(21)14-4-8-16(9-5-14)24-12-2-1-3-13-25-17-10-6-15(7-11-17)19(22)23;;/h4-11H,1-3,12-13H2,(H3,20,21)(H3,22,23);2*1H

4-[5-(4-carbamimidoylphenoxy)pentoxy]benzenecarboximidamide;dihydrochloride

MP-601205 diHCl MP601205 dihydrochloride

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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。