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].

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].

[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

C19H18N2O2

306.36

154447-38-8

LY 303511 hydrochloride;2070014-90-1

O=C1C=C(N2CCNCC2)OC3=C(C4=CC=CC=C4)C=CC=C13

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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).

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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)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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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).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)