| Size | Price | |
|---|---|---|
| 100mg | ||
| 250mg | ||
| 500mg |
| Targets |
Dopamine Receptor
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|---|---|
| ln Vitro |
Dexpramipexole has been found to be neuroprotective and is currently being studied for the treatment of amyotrophic lateral sclerosis (ALS). Dexpramipexole reduces mitochondrial reactive oxygen species (ROS) production, inhibits activation of apoptotic pathways, and increases cell survival against various neurotoxins and beta-amyloid neurotoxicity. Dexpramipexole has much lower dopamine agonist activity than the S-(-) isomer.
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| ln Vivo |
Dexpramipexole increased mitochondrial ATP production in cultured neurons or glia and reduces energy failure, prevents intracellular Ca2+ overload and affords cytoprotection when cultures are exposed to OGD. This compound also counteracted ATP depletion, mitochondrial swelling, anoxic depolarization, loss of synaptic activity and neuronal death in hippocampal slices subjected to OGD. Post‐ischaemic treatment with dexpramipexole, at doses consistent with those already used in ALS patients, reduced brain infarct size and ameliorated neuroscore in mice subjected to transient or permanent MCAo[2].
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| Cell Assay |
Neuronal/astrocytes cultures were prepared from rat embryos (E‐17/E‐19) or pups (P‐1/P‐2), as reported (Chiarugi et al., 2003). Briefly, the cerebral cortex was minced using medium stock (MS) (Eagle's minimal essential medium with Earle's salts, glutamine‐ and NaHCO3‐free, NaHCO3 38 mM, glucose 22 mM, penicillin 100 U·mL−1 and streptomycin 100 µg·mL−1) and then incubated for 10 (neurons) and 45 min (astrocytes) at 37°C in MS supplemented with 0.25% trypsin and 0.05% DNase. Enzymic digestion was terminated by incubation (10 min at 37°C) in MS supplemented with 10% heat‐inactivated horse serum (HIHS) and 10% FBS. Following tissue mechanical disruption, cells were counted and plated. For mixed cortical cell cultures, neurons were re‐suspended at a density of 4 × 105 cells·mL−1 and plated in 15 mm multiwell on a layer of confluent astrocytes using MS supplemented with 10% HIHS, 10% FBS and 2 mM glutamine. After 4–5 days in vitro, non‐neuronal cell division was halted by the application of 3 µM cytosine arabinoside for 24 h. Cell cultures were subjected to oxygen‐glucose deprivation (OGD) in the presence or absence of DEX in a serum‐ and glucose‐free medium saturated with 95% N2 and 5% CO2. Following 2 h of incubation at 37°C in an anoxic chamber, the cultures were transferred to oxygenated serum‐free medium (75% Eagle's minimal essential medium; 25% Hank's balanced salt solution; 2 mM l‐glutamine; 3.75 µg·mL−1 amphotericin B; and 5 mg·mL−1 glucose) and returned to normoxic conditions in the presence or absence of DEX. Propidium iodide (PI) fluorescence was evaluated 24 h later[2].
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| Animal Protocol |
Acute hippocampal slice preparation and OGD exposure[2]
Acute hippocampal slices were prepared from male SD rats (Charles River, Calco, Italy, 150–200 g) as described (Pugliese et al., 2009). Hippocampi were removed and placed in ice‐cold oxygenated artificial CSF of the following composition (mM): NaCl 125, KCl 3, NaH2PO4 1.25, MgSO4 1, CaCl2 2, NaHCO3 25 and D‐glucose 10. Slices of 400 mm were prepared and kept in oxygenated aCSF for at least 1 h at RT. A single slice was then placed on a nylon mesh, completely submerged in a small chamber (0.8 mL) and superfused with oxygenated aCSF (31–32°C) at a constant flow rate of 1.5–1.8 mL·min−1. Under OGD condition, the slice was superfused with aCSF without glucose and gassed with 95%N2–5% CO2. This caused a drop in pO2 in the recording chamber from ~500 mmHg (normoxia) to a range of 35–75 mmHg (after 7 min OGD). (Pugliese et al., 2003) At the end of the ischaemic period, the slice was again superfused with normal, glucose‐containing, oxygenated aCSF. Control slices were not subjected to OGD or drug treatment but were incubated in oxygenated aCSF for identical time intervals. Hippocampal slices were (i) incubated for at least 1 h before electrophysiological recordings in the presence of DEX, which was maintained throughout the experiments or (ii) superfused in the presence of DEX at least 30 min before and after OGD application.
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| References |
[1]. Amyotroph Lateral Scler Frontotemporal Degener. 2013 Jan;14(1):44-51.
[2]. Br J Pharmacol. 2018 Jan; 175(2): 272–283. |
| Additional Infomation |
Dexpramipexole is under investigation in clinical trial NCT01511029 (Study to Evaluate the QTC Interval in Healthy Volunteers Dosed With Dexpramipexole (QTC = Electrocardiogram (ECG) Interval Measured From the Onset of the QRS Complex to the End of the T Wave Corrected for Heart Rate)).
The (R)-(+) enantiomer of PRAMIPEXOLE. Dexpramipexole has lower affinity for DOPAMINE RECEPTORS than pramipexole. |
| Molecular Formula |
C10H17N3S
|
|---|---|
| Molecular Weight |
211.32708
|
| Exact Mass |
211.11
|
| Elemental Analysis |
C, 56.84; H, 8.11; N, 19.88; S, 15.17
|
| CAS # |
104632-28-2
|
| Related CAS # |
Pramipexole dihydrochloride;104632-25-9;Dexpramipexole dihydrochloride;104632-27-1;Dexpramipexole-d3 dihydrochloride;1432230-09-5;Pramipexole;104632-26-0;Pramipexole dihydrochloride hydrate;191217-81-9
|
| PubChem CID |
59868
|
| Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
|
| Density |
1.17±0.1 g/cm3
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| Melting Point |
270-272ºC
|
| LogP |
4.38
|
| tPSA |
83.52
|
| SMILES |
NC1=NC(CC[C@@H](NCCC)C2)=C2S1
|
| InChi Key |
FASDKYOPVNHBLU-SSDOTTSWSA-N
|
| InChi Code |
InChI=1S/C10H17N3S/c1-2-5-12-7-3-4-8-9(6-7)14-10(11)13-8/h7,12H,2-6H2,1H3,(H2,11,13)/t7-/m1/s1
|
| Chemical Name |
NC1=NC2=C(C[C@H](NCCC)CC2)S1
|
| Synonyms |
KNS-760704; (R)-Pramipexole; Dexpramipexole; 104632-28-2; (R)-PRAMIPEXOLE; (R)-N6-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine; R-(+)-Pramipexole; WI638GUS96; (R)-Pramipexole Dihydrochloride; (6R)-6-N-propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine; KNS 760704; KNS760704; Dexpramipexole
|
| HS Tariff Code |
2934.99.9001
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| 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)
|
| Solubility (In Vitro) |
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
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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 | 4.7319 mL | 23.6597 mL | 47.3194 mL | |
| 5 mM | 0.9464 mL | 4.7319 mL | 9.4639 mL | |
| 10 mM | 0.4732 mL | 2.3660 mL | 4.7319 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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