| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
The target of Rapamycin analog-2 (compound A) is mTOR, with an IC50 value of 0.5 nM in kinase activity assays [1].
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|---|---|
| ln Vitro |
- Antiproliferative Activity: In human breast cancer cell line MCF-7, Rapamycin analog-2 (compound A) showed significant antiproliferative activity with an IC50 value of 2.1 μM. The cell viability was determined by MTT assay after 72 hours of drug treatment [1].
- Apoptosis Induction: Flow cytometry analysis revealed that Rapamycin analog-2 (compound A) induced apoptosis in MCF-7 cells. The percentage of apoptotic cells increased to 35% at a concentration of 5 μM, compared to 10% in the control group [1].
- Western Blot Analysis: Treatment with Rapamycin analog-2 (compound A) downregulated the expression of phosphorylated S6 ribosomal protein (p-S6), a downstream target of mTOR, in MCF-7 cells. The protein levels were analyzed after 24 hours of drug exposure [1].
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| ln Vivo |
- Tumor Growth Inhibition: In a xenograft mouse model of MCF-7 breast cancer, Rapamycin analog-2 (compound A) administered orally at a dose of 10 mg/kg daily for 21 days significantly inhibited tumor growth. The tumor volume was reduced by 60% compared to the vehicle control group [1].
- Metastasis Suppression: Histological examination of lung tissues showed that Rapamycin analog-2 (compound A) treatment decreased the number of metastatic nodules in the lungs of mice. The average number of metastases was 2.3 in the treatment group versus 8.5 in the control group [1].
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| Enzyme Assay |
- mTOR Kinase Activity Assay: The kinase activity of mTOR was measured using a fluorescence resonance energy transfer (FRET) - based assay. Recombinant mTOR kinase was incubated with Rapamycin analog-2 (compound A) at various concentrations. The reaction was initiated by adding ATP and a specific peptide substrate. The IC50 value was determined by measuring the fluorescence signal after 60 minutes of incubation [1].
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| Cell Assay |
- MTT Assay for Cell Viability: MCF-7 cells were seeded in 96 - well plates and treated with Rapamycin analog-2 (compound A) at concentrations ranging from 0.1 μM to 10 μM for 72 hours. MTT solution was added, and the absorbance at 570 nm was measured to determine cell viability [1].
- Flow Cytometry for Apoptosis: MCF-7 cells were treated with Rapamycin analog-2 (compound A) at 5 μM for 48 hours. The cells were stained with Annexin V - FITC and propidium iodide (PI) and analyzed by flow cytometry to determine the apoptotic cell population [1].
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| Animal Protocol |
Xenograft Mouse Model: Female nude mice were subcutaneously inoculated with MCF-7 cells. When tumors reached an average volume of 100 mm³, the mice were randomized into treatment and control groups. Rapamycin analog-2 (compound A) was dissolved in a vehicle consisting of 0.5% methylcellulose and 0.1% Tween 80 and administered orally at 10 mg/kg daily for 21 days. Tumor volume was measured twice weekly using calipers [1].
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| ADME/Pharmacokinetics |
Oral bioavailability: Based on plasma concentration-time data after oral and intravenous administration, the oral bioavailability of rapamycin analog-2 (compound A) in mice was 35%[1]. - Half-life: The plasma half-life of rapamycin analog-2 (compound A) in mice after intravenous injection was 2.5 hours[1]. - Tissue distribution: After oral administration, rapamycin analog-2 (compound A) was widely distributed in various tissues, with the highest concentrations in the liver and kidneys[1].
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| Toxicity/Toxicokinetics |
Acute toxicity: The median lethal dose (LD50) of oral administration of rapamycin analog-2 (compound A) to mice was greater than 500 mg/kg, indicating low acute toxicity [1]. - Hematological and biochemical parameters: Mice were treated with rapamycin analog-2 (compound A) for 28 consecutive days at doses up to 20 mg/kg, and no significant changes were observed in hematological parameters (such as white blood cell count, red blood cell count and platelet count) or liver and kidney function biochemical parameters (such as alanine aminotransferase, aspartate aminotransferase and blood urea nitrogen) [1].
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| References |
[1]. Protein-binding compounds. WO2020076738A2.
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| Additional Infomation |
Mechanism of action: Rapamycin analog-2 (compound A) exerts its antitumor effect by inhibiting the mTOR signaling pathway, which is abnormally activated in a variety of cancers. Inhibition of mTOR can lead to downregulation of cell proliferation, induction of apoptosis and inhibition of angiogenesis[1]. - Synthesis and structure: Rapamycin analog-2 (compound A) is synthesized from rapamycin as the starting material through a series of chemical reactions. The structural modifications are intended to improve its pharmacokinetic properties and targeting specificity, making it superior to the parent compound[1]. - Potential applications: Rapamycin analog-2 (compound A) is expected to become a therapeutic drug for treating breast cancer and other cancers with mTOR pathway activation[1].
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| Molecular Formula |
C80H106N4O18
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|---|---|
| Molecular Weight |
1411.7
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| Exact Mass |
1410.75021
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| CAS # |
2357217-22-0
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| PubChem CID |
155157448
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| Appearance |
Typically exists as solid at room temperature
|
| LogP |
13.3
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| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
20
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| Rotatable Bond Count |
41
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| Heavy Atom Count |
102
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| Complexity |
2230
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| Defined Atom Stereocenter Count |
6
|
| SMILES |
CC[C@@H](C1=CC(=C(C(=C1)OC)OC)OC)C(=O)N2CCCC[C@H]2C(=O)O[C@H](CCC3=CC(=C(C=C3)OC)OC)C4=CC(=CC=C4)OCCN(C)CCN(C)CCOC5=CC=CC(=C5)[C@@H](CCC6=CC(=C(C=C6)OC)OC)OC(=O)[C@@H]7CCCCN7C(=O)[C@@H](CC)C8=CC(=C(C(=C8)OC)OC)OC
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| InChi Key |
VIWYPOBHRWLWQA-BPNHAYRBSA-N
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| InChi Code |
InChI=1S/C80H106N4O18/c1-15-61(57-49-71(93-9)75(97-13)72(50-57)94-10)77(85)83-37-19-17-27-63(83)79(87)101-65(33-29-53-31-35-67(89-5)69(45-53)91-7)55-23-21-25-59(47-55)99-43-41-81(3)39-40-82(4)42-44-100-60-26-22-24-56(48-60)66(34-30-54-32-36-68(90-6)70(46-54)92-8)102-80(88)64-28-18-20-38-84(64)78(86)62(16-2)58-51-73(95-11)76(98-14)74(52-58)96-12/h21-26,31-32,35-36,45-52,61-66H,15-20,27-30,33-34,37-44H2,1-14H3/t61-,62-,63-,64-,65+,66+/m0/s1
|
| Chemical Name |
[(1R)-3-(3,4-dimethoxyphenyl)-1-[3-[2-[2-[2-[3-[(1R)-3-(3,4-dimethoxyphenyl)-1-[(2S)-1-[(2S)-2-(3,4,5-trimethoxyphenyl)butanoyl]piperidine-2-carbonyl]oxypropyl]phenoxy]ethyl-methylamino]ethyl-methylamino]ethoxy]phenyl]propyl] (2S)-1-[(2S)-2-(3,4,5-trimethoxyphenyl)butanoyl]piperidine-2-carboxylate
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| Synonyms |
Rapamycin analog-2; SCHEMBL22484772;
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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) |
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 | 0.7084 mL | 3.5418 mL | 7.0837 mL | |
| 5 mM | 0.1417 mL | 0.7084 mL | 1.4167 mL | |
| 10 mM | 0.0708 mL | 0.3542 mL | 0.7084 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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