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| ln Vitro |
ALT-007 (10 nM-10 μM) at 10 nM reduced the level of ceramide in C2C12 myoblasts of immortalized mice, comparable to Myriocin [1].
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| ln Vivo |
ALT-007 (1 mg/kg, orally (mixed with food), once daily for 20 weeks) enhances physical performance in an aged mouse model of sarcopenia, manifested as improved muscle function and aerobic capacity [1]. ALT-007 (1 and 5 μM) improves age-related decline in multiple species, improves protein homeostasis in Caenorhabditis elegans, thereby prolonging lifespan and reducing protein toxicity [1]. ALT-007 (4 mg/kg, orally (mixed with food), once daily for 10 days) is well tolerated and effectively reduces ceramide levels in mouse muscles [1].
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| Animal Protocol |
Animal/Disease Models:Male C57BL/6J mice (18 months old) [1]
Doses: 1 mg/kg Route of Administration: Oral (mixed with food), once daily for 20 weeks Experimental Results: Compared with aged control mice, after 7 and 8 weeks of treatment, the mice showed increased muscle strength, as evidenced by increased maximum suspension time and grip strength. After 9 weeks of treatment, the rotarod test of aged mice showed improved coordination. Maximum oxygen uptake (VO2max) and nocturnal energy expenditure increased significantly. Age-related decline in overall physical activity was fully recovered to levels comparable to those of young mice. Uphill running endurance and post-exercise creatine kinase levels showed a trend toward improvement, but the differences were not significant. Body weight remained stable, with no significant changes in food intake and tissue weight compared with the control group. No gastrointestinal toxicity was observed compared with the untreated control group. There were no differences in glucose tolerance test results compared with the aged control group. Increased lean body mass in aged mice suggests increased muscle mass after 11 weeks. Increased muscle mass in aged mice measured after 20 weeks. Decreased total ceramide levels in aged mice. Affected multiple age-related gene sets, such as mitochondrial and protein homeostasis pathways, amino acid and biosynthetic processes, and neuron-related gene sets. Significantly attenuated ribosome and translation pathways. Promoted enrichment of multiple protein homeostasis pathways (e.g., autophagy, unfolded protein response) in skeletal muscle of aged mice. Led to significant upregulation of neurogenesis pathways in muscle of aged mice. Attenuated the content of long-chain 1-deoxysphingolipids (especially 1-deoxyceramide 22, 1-deoxyceramide 24:1, and sphingosine base N-C24:1-deoxysphingosine) in gastrocnemius muscle. Attenuated the age-related increase in 1-deoxysphingolipid content in brain tissue. Animal/Disease Models:Caenorhabditis elegans strains (GMC-101, CL2120, and CL2122 as controls) [1] Doses: 1 μM Route of Administration: From the embryonic stage Experimental Results: Paralysis caused by amyloid β aggregation was reduced on day 1 of adult assessment. Amyloid β aggregates were reduced. Animal/Disease Models:Male C57BL/6J mice [1] Doses: 4 mg/kg Route of Administration: Oral (mixed with food), once daily for 10 days Experimental Results: There was no difference in body weight and food intake compared with the DMSO control group. Plasma transaminase (AST, ALT) and creatine kinase (CK) levels were comparable to the control group, indicating no liver or muscle toxicity was observed. It effectively reduced ceramide levels in the gastrocnemius muscle, with a more significant effect on very long chain (VLC) ceramides. Animal/Disease Models:Caenorhabditis elegans strain (wild-type Bristol N2) [1] Doses: 5 μM Route of Administration:From day 1 of adulthood Experimental Results:Significantly prolonged median and maximum lifespan. When administered from the embryonic stage, it was non-toxic to animal development, and the animals exhibited normal growth. |
| References |
| Molecular Formula |
C25H26F3N5O5
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|---|---|
| Molecular Weight |
533.50
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| CAS # |
2035010-37-6
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| Appearance |
White to off-white solid
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| SMILES |
O=C(NC1C(N(C(C)C)N=C2)=C2N(C(C3=CN=C(OC)C(OC)=C3)=O)CC1)C4=CC=CC=C4OC(F)(F)F
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| 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)
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| Solubility (In Vitro) |
DMSO : ~25 mg/mL (~46.86 mM; with sonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.69 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you canAdd 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8744 mL | 9.3721 mL | 18.7441 mL | |
| 5 mM | 0.3749 mL | 1.8744 mL | 3.7488 mL | |
| 10 mM | 0.1874 mL | 0.9372 mL | 1.8744 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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