| Size | Price | |
|---|---|---|
| Other Sizes |
Purity: ≥97%
| Targets |
H2S-releasing compound
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|---|---|
| ln Vitro |
S-propargyl-cysteine (SPRC), also named as ZYZ-802, is a structural analog of S-allylcysteine (SAC), the most abundant constituent of aged garlic extract. SPRC becomes a derivative of the amino acid cysteine, which contains sulfur atom, by changing allyl group in SAC to propargyl group in SPRC. Another analog of SPRC and SAC is S-propyl cysteine (SPC), which has propyl group instead in its cysteine structure. Drug formulation of SPRC has been investigated in the mixture of extenders, such as lactose, microcrystalline cellulose, and cross-linked povidone, showing good fluidity and scale-up production possibility. Controlled release formulation of SPRC (CR-SPRC) and leonurine-SPRC were invented and shown the decent pharmacological effects in heart failure and hypoxia injury, respectively. The pharmacological effects of SPRC have been shown that cardioprotection and proangiogenesis in several ischemic heart models, neuroprotection in Alzheimer's disease, proapoptosis in gastric cancer and anti-inflammation in acute pancreatitis. Moreover, CR-SPRC reduced infarct size and recovered partial cardiac function in heart failure rat model. Leonurine-SPRC protected hypoxic neonatal rat ventricular myocytes in much lower dose. Interestingly, since the propagyl group in SPRC has the stronger chemical bond in the cysteine structure than allyl group in SAC and propyl group in SPC, SPRC showed more extensive cardioprotection in ischemic rat hearts model compared to SAC and SPC. The mechanisms of pharmacological effects of SPRC have been unveiled that SPRC reduced Ca2+ accumulation, activated antioxidants, inhibited STAT3, decreased inflammatory cytokines, and elevated p53 and Bax. More pharmacological effects and mechanisms of SPRC will be discovered in atherosclerosis, hypertension, and other diseases[2].
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| ln Vivo |
Hydrogen sulfide (H(2)S), a novel gaseous messenger, is synthesized endogenously from L-cysteine by two pyridoxal-5'-phosphate-dependent enzymes, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). S-propargyl-cysteine (SPRC) is a slow H(2)S releasing drug that provides cysteine, a substrate of CSE. The present study was aimed to investigate the effects of SPRC in an in vivo model of acute pancreatitis (AP) in mice. AP was induced in mice by hourly caerulein injections (50 µg/kg) for 10 hours. Mice were treated with SPRC (10 mg/kg) or vehicle (distilled water). SPRC was administered either 12 h before or 3 h before the induction of pancreatitis. Mice were sacrificed 1 h after the last caerulein injection. Blood, pancreas and lung tissues were collected and processed to measure the plasma amylase, plasma H(2)S, myeloperoxidase (MPO) activities and cytokine levels in pancreas and lung. The results revealed that significant reduction of inflammation, both in pancreas and lung was associated with SPRC given 3 h prior to the induction of AP. Furthermore, the beneficial effects of SPRC were associated with reduction of pancreatic and pulmonary pro-inflammatory cytokines and increase of anti-inflammatory cytokine. SPRC administered 12 h before AP induction did not cause significant improvement in pancreatic and lung inflammation. Plasma H(2)S concentration showed significant difference in H(2)S levels between control, vehicle and SPRC (administered 3 h before AP) treatment groups. In conclusion, these data provide evidence for protective effects of SPRC in AP possibly by virtue of its slow release of endogenous H(2)S[1].
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| Enzyme Assay |
The levels of cytokines (IL-1β, IL-6, IL-10 and TNF-α) were measured in pancreas and lung tissue homogenate by a sandwich ELISA using DuoSet ELISA kits. Briefly, anti-cytokine primary antibodies were coated onto 96-well ELISA plates and incubated overnight at room temperature. Samples and standards were added to the wells and incubated for 2 h, the wells were washed, and a biotinylated goat anti-mouse cytokines antibodies were added for 2 h. Plates were washed again, and streptavidin antibodies conjugated to HRP were added for 20 min. After a further wash, TMB was added for color development, and the reaction was terminated with 2 N H2SO4. Absorbance was measured at 450 nm. Cytokine concentrations of samples were estimated from the standard curve. The cytokine concentration was then corrected for the DNA content of the tissue[2].
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| Animal Protocol |
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]
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| References | |
| Additional Infomation |
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] |
| Molecular Formula |
C6H9NO2S
|
|---|---|
| Molecular Weight |
159.2
|
| Exact Mass |
159.035
|
| Elemental Analysis |
C, 45.27; H, 5.70; N, 8.80; O, 20.10; S, 20.14
|
| CAS # |
3262-64-4
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| PubChem CID |
22789047
|
| Appearance |
Typically exists as Off-white to yellow solids at room temperature
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| Density |
1.284g/cm3
|
| Boiling Point |
294.8ºC at 760 mmHg
|
| Melting Point |
176-178 °C
|
| Flash Point |
132.1ºC
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| Index of Refraction |
1.57
|
| LogP |
0.465
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
10
|
| Complexity |
160
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C#CCSC[C@@H](C(=O)O)N
|
| InChi Key |
JAKVEOCMEMGHGB-YFKPBYRVSA-N
|
| InChi Code |
InChI=1S/C6H9NO2S/c1-2-3-10-4-5(7)6(8)9/h1,5H,3-4,7H2,(H,8,9)/t5-/m0/s1
|
| Chemical Name |
(2R)-2-amino-3-prop-2-ynylsulfanylpropanoic acid
|
| Synonyms |
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
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O : ~25 mg/mL (~157.03 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 6.2814 mL | 31.4070 mL | 62.8141 mL | |
| 5 mM | 1.2563 mL | 6.2814 mL | 12.5628 mL | |
| 10 mM | 0.6281 mL | 3.1407 mL | 6.2814 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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