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5mg |
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25mg |
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Purity: ≥98%
LY303511 is an analog of LY294002 and is also known as NV-128 and EM 101. Unlike LY294002 which is a BET/PI3K inhibitor, LY303511 is a potent mTOR inhibitor. LY303511 inhibits mTOR-dependent cell proliferation without unwanted effects on PI3K. In human lung epithelial adenocarcinoma (A549) cells, LY303511, like rapamycin, inhibited mTOR-dependent phosphorylation of S6K, but not PI3K-dependent phosphorylation of Akt. LY303511 blocked proliferation in A549 as well as in primary pulmonary artery smooth muscle cells, without causing apoptosis. In contrast to rapamycin, LY303511 reduced G(2)/M progression as well as G(2)/M-specific cyclins in A549 cells. Consistent with an additional mTOR-independent kinase target, LY303511 inhibited casein kinase 2 activity, a known regulator of G(1) and G(2)/M progression. In addition to its antiproliferative effect in vitro, LY303511 inhibited the growth of human prostate adenocarcinoma tumor implants in athymic mice. Given its inhibition of cell proliferation via mTOR-dependent and independent mechanisms, LY303511 has therapeutic potential with antineoplastic actions that are independent of PI3K inhibition.
ln Vitro |
LY303511 is essentially identical to LY294002, with the exception that it does not efficiently inhibit PI3K because -O has taken the place of -NH in the morpholine ring. Increased calcein diffusion was seen in cells treated with LY303511, comparable to LY294002 levels. According to immunoblotting, LY303511 can enhance gap junction intercellular communication (GJIC), although this effect does not correspond with a decrease in AKT phosphorylation [1]. SHEP-1 neuroblastoma cells' TRAIL sensitivity is increased by LY303511 via upregulating death receptors and activating H2O2-MAPK. Different concentrations of TRAIL, LY303511 (LY30), and a combination of the two were applied to SHEP-1 cells (preincubation with LY303511 for 1 h, followed by incubation with TRAIL for 4 h). The viable fraction of SHEP-1 cells decreased by roughly 10%, 15%, and 30% at 25, 50, and 100 ng/mL, in response to TRAIL; however, cells treated with 12.5, 25, or 50 μM of LY303511 did not show the same response. Vitality has no impact. On the other hand, LY303511 (25 μM) incubation for one hour and 50 ng/mL TRAIL exposure for four hours resulted in a considerable synergistic impact (about 40% reduction in viable cells with LY303511+TRAIL compared with TRAIL alone), with viable cells declining by around 15%[2]. A negative control for PI3K activity is LY303511. Wortmannin (100 nM) did not affect whole-cell outward K+ currents in MIN6 insulinoma cells, while LY294002 and LY303511 caused the currents to be reversibly inhibited in a dose-dependent manner (IC50 9.0±0.7 μM and 64.6±9.1 μM, respectively). β-cells exhibit high expression levels of Kv2.1 and Kv1.4. In tsA201 cells transfected with Kv2.1, reversible current inhibition was observed at 50 μM LY294002 and 100 μM LY303511, respectively. With an IC50 of 64.6±9.1 µM, LY303511 inhibits current to a maximum of around 90% at 500 µM (n≥5 cells per concentration) [3].
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ln Vivo |
When tumors grow to a volume of about 150 mm3, at which point 35 mice have developed a tumor, intraperitoneal treatment of vehicle or LY303511 (10 mg/kg/day) is carried out. Over 15% of the mice need to be put down after 21 days because to tumor growth that is too rapid; these data are suppressed since average tumor volume estimations are not accurate. It is sufficient to provide 10 mg/kg/day of LY303511 to prevent the formation of PC-3 tumors in vivo[4].
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Animal Protocol |
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References |
[1]. Bodenstine TM, et al. Homotypic gap junctional communication associated with metastasis suppression increases with PKA activity and is unaffected by PI3K inhibition. Cancer Res. 2010 Dec 1;70(23):10002-11.
[2]. El-Kholy W, Macdonald PE, Lin JH, The phosphatidylinositol 3-kinase inhibitor LY294002 potently blocks K(V) currents via a direct mechanism. FASEB J. 2003 Apr;17(6):720-2. [3]. Shenoy K, et al. LY303511 enhances TRAIL sensitivity of SHEP-1 neuroblastoma cells via hydrogen peroxide-mediated mitogen-activated protein kinase activation and up-regulation of death receptors. Cancer Res. 2009 Mar 1;69(5):1941-50. [4]. Kristof AS, et al. LY303511 (2-piperazinyl-8-phenyl-4H-1-benzopyran-4-one) acts via phosphatidylinositol 3-kinase-independent pathways to inhibit cell proliferation via mammalian target of rapamycin (mTOR)- and non-mTOR-dependent mechanisms. J Pharmacol E |
Molecular Formula |
C19H18N2O2
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Molecular Weight |
306.36
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CAS # |
154447-38-8
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Related CAS # |
LY 303511 hydrochloride;2070014-90-1
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Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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SMILES |
O=C1C=C(N2CCNCC2)OC3=C(C4=CC=CC=C4)C=CC=C13
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InChi Key |
NGAGMBNBKCDCDJ-UHFFFAOYSA-N | |
Chemical Name |
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Synonyms |
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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 |
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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) |
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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 | 3.2641 mL | 16.3207 mL | 32.6413 mL | |
5 mM | 0.6528 mL | 3.2641 mL | 6.5283 mL | |
10 mM | 0.3264 mL | 1.6321 mL | 3.2641 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.
LY30 can reduce cell proliferation and sensitize cells treated with low doses of vincristine to apoptosis via an increase in caspase activity.Cancer Res.2005 Jul 15;65(14):6264-74. th> |
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LY30 can reduce cell proliferation and sensitize cells treated with low doses of vincristine to apoptosis via an increase in caspase activity.Cancer Res.2005 Jul 15;65(14):6264-74. td> |
LY30 inhibits the colony-forming ability of cells treated with vincristine.Cancer Res.2005 Jul 15;65(14):6264-74. td> |