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100mg | ||
250mg | ||
500mg |
ln Vitro |
LY-2584702 (LY2584702), having an IC50 of 0.1-0.24 μM, suppresses the phosphorylation of S6 ribosomal protein (pS6) in HCT116 colon cancer cells [1]. The S6K1 enzyme test yields an IC50 value of 2 nM for LY-2584702 (LY2584702). In cells, IC50=100 nM for pS6 inhibition. At high concentrations (IC50=58-176 nM in the enzyme assay), LY-2584702 exhibits specific action against the S6K-related kinases MSK2 and RSK. The phosphorylation of LY-2584702's downstream effector S6 determines how dose-dependently it suppresses S6K activity in EOMA cells [2]. When administered at 0.1 μM for more than 24 hours, LY-2584702 (LY2584702) can considerably limit the proliferation of A549 (P<0.05); additional time under treatment and/or higher drug concentrations make the downward trend more pronounced (both P<0.05). In SK-MES-1, comparable outcomes were noted, but at 0.6 μM Significantly more potent than A549, LY-2584702 showed an inhibitory effect (P<0.05)[3].
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ln Vivo |
Under 2.5 mg/kg twice daily (BID) and 12.5 mg/kg BID, LY-2584702 showed noteworthy single-agent activity in HCT116 colon cancer and U87MG glioblastoma xenograft models. At TMED50 (threshold minimum effective dose 50%) (2.3 mg/kg) and TMED90 (10 mg/kg), LY-2584702 demonstrated statistically significant tumor growth decrease in the HCT116 colon cancer xenograft model [1]. LY-2584702 or rapamycin were administered to shAkt3-expressing EOMA cells implanted into nu/nu mice for a period of 14 days in order to investigate the function of S6K in vivo. LY-2584702 suppressed S6 phosphorylation nearly as well as rapamycin, according to analysis of tumors removed after 14 days. In contrast to pLKO, tumor development was enhanced by Akt3 loss. The growth of pLKO tumors was not substantially impacted by LY-2584702 treatment alone. LY-2584702, however, dramatically slowed the growth of shAkt3 tumors [2].
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References |
[1]. Tolcher A, et al. A phase I trial of LY2584702 tosylate, a p70 S6 kinase inhibitor, in patients with advanced solid tumors. Eur J Cancer. 2014 Mar;50(5):867-75.
[2]. Phung TL, et al. Akt1 and akt3 exert opposing roles in the regulation of vascular tumor growth. Cancer Res. 2015 Jan 1;75(1):40-50. [3]. Chen B, et al. Hyperphosphorylation of RPS6KB1, rather than overexpression, predicts worse prognosis in non-small cell lung cancer patients. PLoS One. 2017 Aug 9;12(8):e0182891 |
Molecular Formula |
C21H20CLF4N7
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Molecular Weight |
481.877016067505
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CAS # |
1082948-81-9
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Related CAS # |
LY-2584702 tosylate salt;1082949-68-5;LY-2584702 free base;1082949-67-4
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SMILES |
CN1C=C(C2=CC=C(F)C(C(F)(F)F)=C2)N=C1C3CCN(C4=C5C(NN=C5)=NC=N4)CC3.[H]Cl
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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 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.) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.0752 mL | 10.3760 mL | 20.7521 mL | |
5 mM | 0.4150 mL | 2.0752 mL | 4.1504 mL | |
10 mM | 0.2075 mL | 1.0376 mL | 2.0752 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.