2. Metabolic Enzyme/Protease
  3. Acyltransferase Ceramidase
  4. ALT-007

ALT-007 is an orally active serine palmitoyltransferase (SPT) inhibitor that selectively reduces the levels of toxic very-long-chain deoxysphingolipids to enhance protein homeostasis. ALT-007 restores aging-related loss of muscle mass in a mouse model of sarcopenia. ALT-007 enhances protein homeostasis in both mouse and C. elegans models of aging and disease. ALT-007 can be used for age-related neuromuscular diseases research.

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ALT-007

ALT-007 Chemical Structure

CAS No. : 2035010-37-6

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Based on 1 publication(s) in Google Scholar

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Description

ALT-007 is an orally active serine palmitoyltransferase (SPT) inhibitor that selectively reduces the levels of toxic very-long-chain deoxysphingolipids to enhance protein homeostasis. ALT-007 restores aging-related loss of muscle mass in a mouse model of sarcopenia. ALT-007 enhances protein homeostasis in both mouse and C. elegans models of aging and disease. ALT-007 can be used for age-related neuromuscular diseases research[1].

IC50 & Target

SPT[1]
In Vitro

ALT-007 (10 nM-10 μM) reduces ceramide levels in immortalized mouse C2C12 myoblasts at 10 nM, comparable to Myriocin (HY-N6798)[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

ALT-007 Related Antibodies
In Vivo

ALT-007 (1 mg/kg, p.o. (mixed with the food), daily for 20 weeks) enhances physical fitness in aged mice model of sarcopenia, evidenced by improved muscle function and aerobic capacity[1].
ALT-007 (1 and 5 μM) ameliorates age-related decline across species, improving proteostasis to extend lifespan and reduce proteotoxicity in C. elegans[1].
ALT-007 (4 mg/kg, p.o. (mixed with the food), daily for 10 days) is well-tolerated and effectively reduces muscle ceramide levels in mice[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Male C57BL/6J mice (18 months old)[1]
Dosage: 1 mg/kg
Administration: p.o. (mixed with the food), daily for 20 weeks
Result: Improved muscle strength, as evidenced by increased maximum hanging time and grip strength compared to aged control mice after 7 and 8 weeks.
Improved coordination measured by the rotarod test in aged mice after 9 weeks.
Significantly increased VO2max and nightly energy expenditure.
Completely restored the age-related decline in overall physical activity to levels comparable to young mice.
Showed a non-significant trend toward improvement in uphill running endurance and post-exercise creatine kinase levels.
Showed stable body weight and no significant changes in food intake and in tissue weights relative to control.
Displayed no gastrointestinal (GI) toxicity compared to untreated controls.
Showed no difference in the glucose tolerance test compared to the aged control group.
Increased lean mass in aged mice, suggesting elevated muscle mass after 11 weeks.
Increased muscle weight in aged mice measured after 20 weeks.
Displayed lower levels of total ceramides in aged mice.
Impacted several age-related gene sets such as mitochondrial and proteostasis pathways, amino acids and biosynthetic processes, and neuronal-related gene sets.
Significantly attenuated ribosomal and translation pathways.
Promoted the enrichment of several proteostasis pathways (e.g., autophagy, unfolded protein response) in skeletal muscle of aged mice.
Resulted in remarkable upregulation of neurogenesis pathways in the muscle of aged mice.
Attenuated 1-Deoxy-SLs of very long chain, particularly 1-deoxyCer 22, 1-deoxyCer 24:1 and the sphingoid base N−C24:1-deoxysphinganine in the gastrocnemius muscle.
Attenuated the age-related increase in 1-deoxy-SLs in the brain.
Animal Model: C. elegans Strains (GMC-101, CL2120, and CL2122 as a control)[1]
Dosage: 1 μM
Administration: from the embryonic stage
Result: Reduced paralysis induced by amyloid beta aggregation when assessed at day 1 of adulthood.
Decreased amyloid-beta protein aggregates.
Animal Model: Male C57BL/6J mice[1]
Dosage: 4 mg/kg
Administration: p.o. (mixed with the food), daily for 10 days
Result: Showed no differences in body weight and food intake compared to DMSO control mice.
Displayed no hepatic or muscle toxicity, as indicated by plasma levels of transaminases (AST, ALT) and creatine kinase (CK) comparable to controls.
Effectively decreased ceramide levels in the gastrocnemius muscle, with a stronger effect on very long-chain (VLC) species.
Animal Model: C. elegans Strains (wild-type Bristol N2)[1]
Dosage: 5 μM
Administration: starting from day 1 of adulthood
Result: Significantly increased median and maximal lifespan.
Was non-toxic for animal development when administered from the embryo stage, with animals exhibiting normal growth.
Molecular Weight

533.50

Formula

C25H26F3N5O5
CAS No.
Appearance

Solid

Color

White to off-white

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
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 25 mg/mL (46.86 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 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
View the 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. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

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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.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    90% Corn Oil

    Solubility: ≥ 2.5 mg/mL (4.69 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

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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Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
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
References

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. 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 1.8744 mL 9.3721 mL 18.7441 mL 46.8604 mL
5 mM 0.3749 mL 1.8744 mL 3.7488 mL 9.3721 mL
10 mM 0.1874 mL 0.9372 mL 1.8744 mL 4.6860 mL
15 mM 0.1250 mL 0.6248 mL 1.2496 mL 3.1240 mL
20 mM 0.0937 mL 0.4686 mL 0.9372 mL 2.3430 mL
25 mM 0.0750 mL 0.3749 mL 0.7498 mL 1.8744 mL
30 mM 0.0625 mL 0.3124 mL 0.6248 mL 1.5620 mL
40 mM 0.0469 mL 0.2343 mL 0.4686 mL 1.1715 mL
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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

ALT-0072035010-37-6ALT007ALT 007AcyltransferaseCeramidaseDiacylglycerol acyltransferaseDiglyceride acyltransferaseacyl-CoA:cholesterol acyltransferasemono- acylglycerol acyltransferaseSPTvery-long-chain deoxysphingolipidsprotein homeostasisaging-relatedsarcopeniaC. elegansneuromuscularInhibitorinhibitorinhibit

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