| ln Vitro |
VU6008055 significantly enhanced acetylcholine-induced calcium mobilization in CHO cells expressing human M4, with an EC50 of 73.4 nM and a maximum response of 91% of the maximum response of acetylcholine[1]. VU6008055 also significantly enhanced acetylcholine-induced calcium mobilization in CHO cells expressing rat M4, with an EC50 of 19.5 nM and a maximum response of 81% of the maximum response of acetylcholine[1]. VU6008055 did not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A4 at concentrations up to 15 μM, and did not cause time-dependent CYP inhibition[1]. VU6008055 did not form active intermediates/metabolites in human liver microsomes[1]. VU6008055 (10 μM) had no significant inhibitory activity on cardiac ion channels[1]. VU6008055 (4 h) showed moderate metabolic turnover in human hepatocytes, and low to high metabolic turnover in other preclinical animal models, and formed two major metabolites (MT4 and MT5) in humans[1].
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| ln Vivo |
VU6008055 (0.1–10 mg/kg; orally) dose-dependently blocked amphetamine-induced hyperactivity in male Sprague-Dawley rats, with the lowest effective dose being 0.3 mg/kg and up to 63% reversing hyperactivity at 10 mg/kg [1]. VU6008055 (0.3–3 mg/kg; orally) attenuated MK-801-induced hyperactivity in male Sprague-Dawley rats [1]. VU6008055 (3 mg/kg; orally; twice daily for 7 days) did not induce tolerance to antipsychotic-like activity in male Sprague-Dawley rats and reversed approximately 50.6% of amphetamine-induced hyperactivity [1]. VU6008055 (0.3–30 mg/kg; orally) had only a slight interfering effect on conditioned avoidance responses in male Wistar-Han rats at high doses (30 mg/kg) and no significant effect at low doses [1]. VU6008055 (1–10 mg/kg; orally) dose-dependently blocked amphetamine-induced brain activation in male Sprague-Dawley rats [1]. VU6008055 (0.1–10 mg/kg; orally) dose-dependently increased high-frequency gamma wave power in awake male Sprague-Dawley rats, which is a marker of EEG arousal [1].
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| Animal Protocol |
Animal/Disease Models:Sprague-Dawley (male) [1]
Doses: 0.1 mg/kg; 0.3 mg/kg; 0.56 mg/kg; 1 mg/kg; 3 mg/kg; 10 mg/kg Route of Administration: Oral Experimental Experimental Results: Significant dose-dependent blocking effect on amphetamine-induced hypermotility, with mean reversal rates of 8.1% (0.1 mg/kg), 33% (0.3 mg/kg), 26% (0.56 mg/kg), 51% (1 mg/kg), 44% (3 mg/kg) and 63% (10 mg/kg), respectively. Mean free brain concentrations ranged from 0.71 nM (0.1 mg/kg) to 68.6 nM (10 mg/kg). Animal/Disease Models:Sprague-Dawley mice (male) [1] Doses: 0.3 mg/kg; 1 mg/kg; 3 mg/kg Route of Administration: Oral Experimental Experimental Results: It can alleviate MK-801-induced hyperactivity, with average reversal rates of 7.4% (0.3 mg/kg), 24.3% (1 mg/kg) and 49.1% (3 mg/kg), respectively. The 3 mg/kg dose group was statistically significant. Animal/Disease Models:Sprague-Dawley mice (male) [1] Doses: 3 mg/kg Route of Administration: Oral; twice daily; for 7 days Experimental Results: Long-term administration reduced amphetamine-induced hyperactivity by 50.6%. The degree of inhibition was similar to the 45.7% inhibition observed after a single acute dose of 3 mg/kg. Animal/Disease Models:Wistar-Han (male) [1] Doses: 0.3 mg/kg; 1 mg/kg; 3 mg/kg; 10 mg/kg; 30 mg/kg Route of Administration: Oral Experimental Results: The effect on avoidance and escape responses at a dose of 30 mg/kg was only moderate. Lower doses (0.3–10 mg/kg) did not significantly interfere with avoidance responses compared to the solvent control group. Animal/Disease Models:Sprague-Dawley mice (male) [1] Doses: 1 mg/kg; 10 mg/kg Route of Administration: Oral Experimental Results: The dose-dependent increase in cerebral blood volume (CBV) induced by amphetamine in the putamen caudate, nucleus accumbens, prefrontal cortex, cingulate cortex, dorsal medial nucleus of the thalamus, and ventroposterolateral/ventroposteromedial nucleus of the thalamus was attenuated. No significant CBV response was observed when administered alone. Animal/Disease Models:Sprague-Dawley mice (male) [1] Doses: 0.1 mg/kg; 0.3 mg/kg; 1 mg/kg; 3 mg/kg; 10 mg/kg Route of Administration: Oral Experimental Experimental Results: High gamma wave power (30-100 Hz) was significantly increased during the awake period in a dose-dependent manner. The high gamma wave power was significantly increased in the 0.3 mg/kg (78-79 Hz, 80-100 Hz), 1 mg/kg (78-100 Hz), 3 mg/kg (89-100 Hz) and 10 mg/kg (80-100 Hz) dose groups. |
| References |
| Molecular Formula |
C20H21N5OS
|
|---|---|
| Molecular Weight |
379.48
|
| CAS # |
2170551-59-2
|
| Appearance |
Off-white to light yellow solid
|
| SMILES |
CC1=NN=C(SC2=C3N=CN=C2NCC4=CC=C(C(C)(O)C)C=C4)C3=C1C
|
| Synonyms |
AF98943
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~263.52 mM; with sonication)
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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 | 2.6352 mL | 13.1759 mL | 26.3518 mL | |
| 5 mM | 0.5270 mL | 2.6352 mL | 5.2704 mL | |
| 10 mM | 0.2635 mL | 1.3176 mL | 2.6352 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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