SPRC   中文名称: L-炔丙基半胱氨酸

H2S-releasing compound

S-炔丙基半胱氨酸（SPRC），也称为ZYZ-802，是S-烯丙基半胱氨酸（SAC）的结构类似物，SAC是陈年大蒜提取物中含量最丰富的成分。通过将SAC中的烯丙基改为SPRC中的炔丙基，SPRC成为含有硫原子的氨基酸半胱氨酸的衍生物。SPRC和SAC的另一个类似物是S-丙基半胱氨酸（SPC），其半胱氨酸结构中有丙基。SPRC的药物配方已在乳糖、微晶纤维素和交联聚维酮等填充剂的混合物中进行了研究，显示出良好的流动性和扩大生产的可能性。发明了SPRC（CR-SPRC）和益母草SPRC的控释制剂，并分别在心力衰竭和缺氧损伤中显示出良好的药理作用。SPRC的药理作用机制已被揭示，SPRC减少了Ca2+的积累，激活了抗氧化剂，抑制了STAT3，减少了炎性细胞因子，提高了p53和Bax。在动脉粥样硬化、高血压和其他疾病中，将发现更多的SPRC药理作用和机制。[2]

硫化氢（H（2）S）是一种新型的气态信使，由L-半胱氨酸通过两种吡哆醛-5'-磷酸依赖酶胱硫醚β-合酶（CBS）和胱硫醚γ-裂解酶（CSE）内源性合成。S-炔丙基半胱氨酸（SPRC）是一种缓慢释放H（2）S的药物，提供半胱氨酸，半胱氨酸是CSE的底物。本研究旨在探讨SPRC在小鼠急性胰腺炎（AP）体内模型中的作用。通过每小时注射50µg/kg的蓝蛙素10小时在小鼠体内诱导AP。用SPRC（10mg/kg）或赋形剂（蒸馏水）治疗小鼠。在胰腺炎诱导前12小时或3小时给予SPRC。在最后一次注射蓝蛙素后1小时处死小鼠。采集血液、胰腺和肺组织并进行处理，以测量胰腺和肺中的血浆淀粉酶、血浆H（2）S、髓过氧化物酶（MPO）活性和细胞因子水平。结果显示，胰腺和肺部炎症的显著减少与AP诱导前3小时给予SPRC有关。此外，SPRC的有益作用与胰腺和肺促炎细胞因子的减少以及抗炎细胞因子的增加有关。在AP诱导前12小时给予SPRC并没有显著改善胰腺和肺部炎症。对照组、赋形剂组和SPRC（AP前3小时给药）治疗组的血浆H（2）S浓度存在显著差异。综上所述，这些数据为SPRC在AP中的保护作用提供了证据，这可能是由于其缓慢释放内源性H（2）S。[1]

使用DuoSet ELISA试剂盒通过夹心ELISA测定胰腺和肺组织匀浆中细胞因子（IL-1β、IL-6、IL-10和TNF-α）的水平。简而言之，将抗细胞因子一抗涂覆在96孔ELISA板上，并在室温下孵育过夜。将样品和标准品加入孔中并孵育2小时，洗涤孔，加入生物素化的山羊抗小鼠细胞因子抗体2小时。再次洗涤板，加入与HRP结合的链霉抗生物素蛋白抗体20分钟。进一步洗涤后，加入TMB进行显色，用2 N H2SO4终止反应。在450nm处测量吸光度。根据标准曲线估算样品的细胞因子浓度。然后根据组织的DNA含量校正细胞因子浓度[2]。

Mice were randomly assigned to four groups (n = 10 per group). Group 1: Animals were given hourly intraperitoneal (i.p.) injections of normal saline (CTRL group). Group 2: Animals were treated with distilled water (DW) followed by hourly i.p. injections of caerulein (50 µg/kg) over 10 h to induce AP (Veh+Cae). Group 3: Animals were treated with SPRC (10 mg/kg), 3 h before hourly injections of caerulein (50 µg/kg) over 10 h (SPRC 3 h+Cae). Group 4: Animals were treated with SPRC (10 mg/kg), 12 h before hourly injections of caerulein (50 µg/kg) over 10 h (SPRC 12 h+Cae). SPRC was dissolved in DW. One hour after the last caerulein injection animals were sacrificed by an i.p. injection of a lethal dose of pentobarbital (50 mg/kg: Nembutal). Blood, pancreas and lung tissues were collected. Samples of pancreas and lung were weighed, snap frozen in liquid nitrogen and then stored at −80°C for subsequent measurement of tissue myeloperoxidase (MPO) activities, and cytokines as described in detail below. Harvested heparinized blood was centrifuged (10,000 rpm, 10 min, 4°C) and the plasma was aspirated and stored at −80°C for subsequent detection of plasma amylase and H2S. Parts of the pancreas and lung were also fixed in 10% v/v neutral phosphate-buffered formalin for more than 48 h and then were processed for histology.[2]

[1]. Effects of S-propargyl-cysteine (SPRC) in caerulein-induced acute pancreatitis in mice. PLoS One. 2012;7(3):e32574.

[2]. The Pharmacological Effects of S-Propargyl-Cysteine, a Novel Endogenous H2S-Producing Compound. Handb Exp Pharmacol. 2015;230:325-36.

Furthermore, we investigated if SPRC treatment affected plasma H2S levels in AP and the mechanism by which inflammation was modulated by SPRC. SPRC, like SAC, could potentially influence the synthesis of endogenous H2S. In vitro, SPRC was found to increase H2S synthesizing enzyme activity in normal pancreatic acini compared to the vehicle control, but the difference was not significant in the presence of caerulein hyper-stimulation (unpublished data). However, while we observed a significant increase in plasma H2S concentration in AP-induced mice treated with vehicle, SPRC injected 3 h before AP lowered this increase. As expected, high plasma H2S concentration observed in vehicle treated mice after induction of AP was pro-inflammatory and damaging. Administration of SPRC 3 h before AP induction and thus the slow release of H2S could have inhibited CSE by a feedback mechanism resulting in significantly lower levels of H2S compared to the vehicle treated mice. Administration of a slow H2S releasing compound has previously been shown to be associated with a decrease in endogenous H2S formation. Evidently, further studies are needed to explore the mechanisms of SPRC effects in AP in detail.
In conclusion, SPRC 10 mg/kg injected 3 h prior to induction of AP ameliorated the disease by reducing the inflammatory cell infiltration in pancreas and lung and by modulating pro- and anti-inflammatory cytokine profile in plasma. Thus SPRC provides a valuable lead for the treatment of AP. It could be postulated that the beneficial effects of SPRC in AP could be by virtue of its slow release of endogenous H2S and a possible negative feedback mechanism on CSE.[2]

C6H9NO2S

159.2

159.035

C, 45.27; H, 5.70; N, 8.80; O, 20.10; S, 20.14

3262-64-4

22789047

Typically exists as Off-white to yellow solids at room temperature

1.284g/cm3

294.8ºC at 760 mmHg

176-178 °C

132.1ºC

1.57

0.465

88.62

2

4

4

10

160

1

C#CCSC[C@@H](C(=O)O)N

JAKVEOCMEMGHGB-YFKPBYRVSA-N

InChI=1S/C6H9NO2S/c1-2-3-10-4-5(7)6(8)9/h1,5H,3-4,7H2,(H,8,9)/t5-/m0/s1

(2R)-2-amino-3-prop-2-ynylsulfanylpropanoic acid

S-Propargyl-cysteine; (R)-2-Amino-3-(2-propynylthio)propanoic Acid; (R)-2-Amino-3-(prop-2-yn-1-ylthio)propanoic acid; s-propargyl-cysteine; (R)-2-Amino-3-(prop-2-ynylthio)propanoic acid; SPRC; s-propargylcysteine; (L)-3-(PROPARGYLSULFENYL)-ALANINE; SPRC

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 : ~25 mg/mL (~157.03 mM)

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。