| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Leptin receptor (ObR), a member of the class I cytokine receptor family. Allo-aca binds to ObR with high affinity and specificity, blocking the binding of the natural hormone leptin. This antagonism prevents activation of downstream signaling pathways including JAK2/STAT3, PI3K/Akt, and MAPK/ERK.
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| ln Vitro |
At 50 pM, allo-aca suppresses the growth of MDA-MB-231 cells induced by leptin. With an IC50 of 200 pM, allo-aca suppresses the proliferation of MCF-7 cells caused by leptin[1]. In both cell lines, VEGF-dependent leptin mRNA expression was lowered below basal levels by allo-aca at a dose of 250 nmol/L. Allo-aca prevents VEGF from having its mitogenic effects. In RF/6A retinal endothelial cells, allo-aca inhibits VEGF-induced chemotaxis and chemotaxis [2].
In RF/6A cells, Allo-aca (250 nM) inhibits VEGF-induced signaling pathways. In LNCaP prostate cancer cells, Allo-aca blocks leptin-induced cell survival signaling. It shows picomolar activities in various cellular systems, with very tight binding to the leptin receptor preventing leptin-mediated effects. |
| ln Vivo |
The mean survival period in the MDA-MB-231 orthotopic mice xenograft model was considerably extended from 15.4 days (untreated control) to 24 days and 28.1 days after subcutaneous injection of Allo-aca at dosages of 0.1 and 1 mg/kg/day, respectively[1].
Allo-aca inhibits LNCaP xenograft tumor growth in mice. It blocks leptin signaling in vivo, reduces tumor cell survival, and induces apoptosis. Sub-mg/kg subcutaneous doses show efficacy in animal models, making it a prime drug candidate and target validation tool for diseases where leptin signaling is pathogenic. |
| Enzyme Assay |
Surface plasmon resonance (SPR) or radioligand binding assays using recombinant leptin receptor extracellular domain. Competition binding experiments with 125I-labeled leptin and varying concentrations of Allo-aca determine IC50 and Ki values. Receptor binding kinetics can be measured by SPR with immobilized ObR.
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| Cell Assay |
LNCaP or other leptin-responsive cancer cell lines are cultured in serum-free medium and stimulated with leptin (10-50 ng/mL) in the presence or absence of Allo-aca (250 nM for 15 min to 24 h). Downstream signaling proteins (p-STAT3, p-ERK, p-Akt) are analyzed by Western blot. Cell proliferation and apoptosis are measured.
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| Animal Protocol |
In LNCaP xenograft models, Allo-aca is administered subcutaneously at sub-mg/kg doses daily or weekly. Tumor volume is measured every 2-3 days. Tumor lysates are analyzed for signaling proteins and cell cycle markers. Body weight, food intake (if hypothalamic), and serum leptin levels may be measured.
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| ADME/Pharmacokinetics |
Allo-aca has a relatively short serum half-life (undetectable after 24 hours in mouse plasma). However, it compensates for this with very tight binding to the leptin receptor, allowing for sustained target engagement. It is administered subcutaneously for in vivo studies.
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| Toxicity/Toxicokinetics |
In preclinical studies, Allo-aca is well-tolerated at therapeutic doses. No significant off-target toxicity or systemic adverse effects have been reported. H&E staining of major organs shows no abnormalities. Higher doses may produce leptin deficiency-like effects.
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| References |
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| Additional Infomation |
Allo-aca is a validated tool for investigating the role of leptin signaling in cancer, obesity, and metabolic disorders. It has been shown to inhibit prostate tumor growth in animal models. It is not FDA-approved and is strictly for research use.
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| Molecular Formula |
C48H75N13O15
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|---|---|
| Molecular Weight |
1074.19
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| Related CAS # |
Allo-aca TFA
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| Appearance |
White to off-white solid powder
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
H2O :~50 mg/mL (~46.55 mM)
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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 | 0.9309 mL | 4.6547 mL | 9.3093 mL | |
| 5 mM | 0.1862 mL | 0.9309 mL | 1.8619 mL | |
| 10 mM | 0.0931 mL | 0.4655 mL | 0.9309 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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