zr17-2
Based on 1 Customer Validation
zr17-2 is a molecule that mimics a hypothermic state. zr17-2 binds RBM3/CIRBP, selectively enhances RBM3 rather than CIRP, and blocks CIRBP degradation. Zr17-2 significantly increases DHODH expression and decreases PTGS2 expression. zr17-2 inhibits pro-inflammatory markers. zr17-2 improves post-transplantation function and mitochondrial function of aged donor hearts. zr17-2 can be used in research on ischemic stroke, perinatal asphyxia, myocardial injury, and traumatic optic neuropathy.
For research use only. We do not sell to patients.
- Purity : 98.01%
- CAS No.: 1263893-98-6
- Formula: C13H20N6O2S
- Molecular Weight:324.40
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Storage:
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[4]|
COX-2 |
In Vitro
zr17-2 (10 µM; 4 days) increases CIRBP protein expression more effectively at 37°C than at low temperature in R28 cells[2].
zr17-2 (0-30 μM) increases RBM3 protein levels in BV2 microglial cells but does not increase CIRP protein levels[5].
zr17-2 (0-10 μM) inhibits OGD-induced cell death in OBSC[5].
zr17-2 (3 μM) promotes neuronal survival in OBSC after OGD[5].
zr17-2 has no activity against CK2[6].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:R28 cells
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Concentration:10 µM
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Incubation Time:4 days
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Result:Compounds zr17-2 and SD4 significantly elevated CIRBP protein expression in R28 cells at 37°C, with zr17-2 being more efficient than hypothermia itself.
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Cell Line:R28 cells
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Concentration:0.1-250 µM
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Incubation Time:4 days (zr17-2); 2 h (MTS)
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Result:No loss of cell viability was found at 250 µM after 4 days.
In Vivo
zr17-2 (330 nmol/L in 5.0 µL; intravitreal injection; single dose) significantly reduces electrophysiological, morphological, and apoptotic retinal damage after orbital optic nerve crush in rats[6].
zr17-2 (20 μmol/kg; intraperitoneal injection; once after suture/recovery) has neuroprotective and anti-inflammatory effects in a mouse model of photothrombotic stroke, reducing infarction and improving functional recovery while promoting neuronal survival, microglial proliferation, and neurogenesis[5].
zr17-2 (50 µL of 330 nmol/L; subcutaneous injection; single injection) has no detectable effect on retinal ERG or morphology in normally delivered neonatal male Sprague-Dawley rats[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley albino (male)[2]
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Dosage:20 nmols/Kg
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Administration:i.p.; single injection
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Result:Elevated CIRBP expression in most peripheral tissues studied: lung, testis, heart, colon, pancreas, and subcutaneous fat.
In heart, control samples showed an immunoreactive smear of lower molecular weight; after zr17-2 administration, this smear was reduced and the expected ~19 kD CIRBP band appeared.
Brain cortex, other areas of the central nervous system, and retina showed small or no change in CIRBP expression.
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Animal Model:Sprague-Dawley (albino, male pups, newborn)[3]
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Dosage:50 µL of 330 nmols/L
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Administration:s.c.; single injection
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Result:In PA rats, zr17-2 recovered ERG a-wave, b-wave, and oscillatory potentials; recovery was complete for oscillatory potentials and partial for a- and b-waves.
PA increased TUNEL-positive cells in the GCL about 6-fold versus CTL; zr17-2 reduced the number of TUNEL-positive cells, although it remained above control levels.
PA increased inner retina thickness; zr17-2 reduced this thickening, although the value remained higher than in controls.
PA increased GFAP immunoreactivity in the outer plexiform layer, GCL, and inner limiting membrane; zr17-2 reduced gliosis to levels comparable to controls.
No apparent adverse reactions were observed in animals given zr17-2.
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Animal Model:Sprague-Dawley (albino, male pups, newborn)[3]
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Dosage:50 µL of 330 nmols/L
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Administration:s.c.; single injection
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Result:In normally delivered rats, zr17-2 did not alter the ERG profile.
Did not modify the number of TUNEL-positive cells in the GCL.
Produced no changes in inner retina thickness.
Had no effect on the measured retinal parameters, suggesting a lack of toxicity.
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Animal Model:Sprague-Dawley (SD) (male; donor rats 1 year old; recipient rats 10 weeks old)[4]
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Dosage:36 μg/100 mL in UW cardioplegic solution
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Administration:ex vivo donor heart preservation in cardioplegic solution; once; during arrest and 6-hour cold storage at 4°C
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Result:CIRBP expression was significantly increased in aged donor hearts after the addition of Zr17-2.
The addition of Zr17-2 to the cardioplegic solution significantly shortened the time to restore sinus rhythm and improved the beating score after transplantation.
This agonist also significantly improved the postoperative cardiac function of aged donor hearts 1 day and 7 days after transplantation, as indicated by the significant increases in EF, FS, max dp/dt, min dp/dt, and CI and the decrease in LVEDP.
Moreover, the addition of Zr17-2 to the cardioplegic solution significantly alleviated the changes in serum cardiac enzymes in the recipients that were transplanted with aged donor hearts.
Furthermore, MPO, H&E, and PTAH staining revealed that neutrophil infiltration and myocardial contraction band necrosis were alleviated after the addition of Zr17-2.
In addition, Zr17-2 significantly increased the expression of DHODH and the ratio of CoQH2 to CoQ in aged donor hearts after transplantation.
As a result, the levels of MDA, 4-HNE, iron, and arachidonic acid metabolites were significantly decreased in aged donor hearts after transplantation.
Prussian blue staining also showed that iron deposition was decreased in aged donor hearts after Zr17-2 supplementation.
Finally, Zr17-2 significantly decreased the expression of PTGS2 in aged donor hearts.
Electron microscopy showed that ferroptosis-related mitochondrial changes in aged donor hearts were mitigated by the addition of Zr17-2.
Notably, the Seahorse assay showed that Zr17-2 significantly increased mitochondrial function in aged donor hearts.
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Animal Model:C57BL/6J (wild-type, 12-week-old, male)[5]
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Dosage:20 μmol/kg
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Administration:intraperitoneal injection; once after suturing/recovery
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Result:In animals treated with zr17-2, infarction volume was significantly reduced compared to DMSO control.
After zr17-2 administration, a higher number of surviving neurons was observed in the infarction core, and the neuronal number recovered to a level comparable to that of the contralateral site in the peri-infarction zone.
At the third and seventh days after stroke, animals treated with zr17-2 showed reduced mNSS score and improved motor coordination on rotarod compared to control mice.
In the zr17-2 group, the intensity of Iba1 was reduced in the peri-infarction zone but not in the infarction core, while microglia number was increased in both the peri-infarction zone and the infarction core.
As expected, the number of proliferating NSCs was elevated in the peri-infarction zone after zr17-2 administration compared to mock control.
Enhanced RBM3 level in both the contralateral and ipsilateral sites, particularly in the peri-infarction zone where microglia and astrocyte accumulate.
In contrast, CIRP level was only slightly increased in the contralateral site, but not in the injured region.
Instead, zr17-2 remarkably reduced Il-1b and iNOS levels.
The IL-1β protein level was correspondingly suppressed in the infarction core in the zr17-2 group.
The expressions of anti-inflammatory Il-10 and Arg1 mRNA were both decreased in the infarction core and peri-infarction zone in control animals, but they were recovered after zr17-2 administration.
Consistently, the IL-10 protein level was also upregulated by zr17-2.
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Animal Model:Sprague-Dawley albino (male, 8-week-old)[6]
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Dosage:330 nmol/L; 5.0 µl
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Administration:intravitreal injection; single
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Result:Injection of zr17-2 in IONC-damaged eyes resulted in a significant recovery of the b-wave and oscillatory potentials.
The a-wave reduction was not prevented by injection with zr17-2.
Injection of zr17-2 resulted in a significant prevention of RGC loss in the GCL, although these values were still lower than the controls.
Administration of zr17-2 greatly reduced TUNEL-positive apoptotic cells in the GCL and INL, although these did not reach basal levels.
Chemical Information
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CAS No. 1263893-98-6
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Appearance Solid
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Molecular Weight 324.40
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Formula C13H20N6O2S
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Color White to off-white
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SMILES
O=C(O)CSC1=C2N=CN(CCN(CC)CC)C2=NC(N)=N1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
Solvent & Solubility
In Vitro:
DMSO : ≥ 100 mg/mL (308.26 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (7.71 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (7.71 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
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Data Sheet (294 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Handling Instructions (2659 KB)
References
[2]. Coderch C, et al. In silico identification and in vivo characterization of small molecule therapeutic hypothermia mimetics. Bioorganic & medicinal chemistry. 2017 Dec 15;25(24):6597-6604. [Content Brief]
[6]. Contartese DS, et al. A hypothermia mimetic molecule (zr17-2) reduces ganglion cell death and electroretinogram distortion in a rat model of intraorbital optic nerve crush (IONC). Frontiers in pharmacology. 2023;14:1112318. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 3.0826 mL | 15.4131 mL | 30.8261 mL | 77.0654 mL |
| 5 mM | 0.6165 mL | 3.0826 mL | 6.1652 mL | 15.4131 mL | |
| 10 mM | 0.3083 mL | 1.5413 mL | 3.0826 mL | 7.7065 mL | |
| 15 mM | 0.2055 mL | 1.0275 mL | 2.0551 mL | 5.1377 mL | |
| 20 mM | 0.1541 mL | 0.7707 mL | 1.5413 mL | 3.8533 mL | |
| 25 mM | 0.1233 mL | 0.6165 mL | 1.2330 mL | 3.0826 mL | |
| 30 mM | 0.1028 mL | 0.5138 mL | 1.0275 mL | 2.5688 mL | |
| 40 mM | 0.0771 mL | 0.3853 mL | 0.7707 mL | 1.9266 mL | |
| 50 mM | 0.0617 mL | 0.3083 mL | 0.6165 mL | 1.5413 mL | |
| 60 mM | 0.0514 mL | 0.2569 mL | 0.5138 mL | 1.2844 mL | |
| 80 mM | 0.0385 mL | 0.1927 mL | 0.3853 mL | 0.9633 mL | |
| 100 mM | 0.0308 mL | 0.1541 mL | 0.3083 mL | 0.7707 mL |
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