1. Apoptosis Membrane Transporter/Ion Channel
  2. TNF Receptor Potassium Channel
  3. LY 303511 hydrochloride

LY 303511 hydrochloride is a structural analogue of LY294002. LY303511 does not inhibit PI3K. LY303511 enhances TRAIL sensitivity of SHEP-1 neuroblastoma cells. LY303511 reversibly blocks K+ currents (IC50=64.6±9.1 μM) in MIN6 insulinoma cells.

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LY 303511 hydrochloride Chemical Structure

LY 303511 hydrochloride Chemical Structure

CAS No. : 2070014-90-1

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Solid + Solvent
10 mM * 1 mL in DMSO
ready for reconstitution
USD 105 In-stock
Solution
10 mM * 1 mL in DMSO USD 105 In-stock
Solid
5 mg USD 95 In-stock
10 mg USD 160 In-stock
50 mg USD 610 In-stock
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Customer Review

Based on 2 publication(s) in Google Scholar

Other Forms of LY 303511 hydrochloride:

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  • Biological Activity

  • Protocol

  • Purity & Documentation

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Description

LY 303511 hydrochloride is a structural analogue of LY294002. LY303511 does not inhibit PI3K. LY303511 enhances TRAIL sensitivity of SHEP-1 neuroblastoma cells. LY303511 reversibly blocks K+ currents (IC50=64.6±9.1 μM) in MIN6 insulinoma cells.

IC50 & Target

TRAIL[2]
IC50: 64.6±9.1 µM (K+ currents, in MIN6 insulinoma cells)[3]

In Vitro

LY303511 is structurally identical to LY294002 except for a substitution of -O for -NH in the morpholine ring, and does not potently inhibit PI3K. Treatment of cells with LY303511 causes an increase in calcein spread similar to levels of LY294002. The ability of LY303511 to increase gap junctional intercellular communication (GJIC) does not occur concomitant with inhibition of phosphorylation of AKT as measured by immunoblotting[1]. LY303511 enhances TRAIL sensitivity of SHEP-1 neuroblastoma cells via H2O2-MAPK activation and up-regulation of death receptors. SHEP-1 cells are exposed to varying concentrations of LY303511 (LY30), TRAIL, and a combination of the two (1 h preincubation with LY303511 followed by TRAIL for 4 hours). SHEP-1 cells are responsive to TRAIL (~10%, ~15%, and ~30% reduction in the surviving fraction at 25, 50, and 100 ng/mL, respectively); however, treatment with LY303511 (12.5, 25, or 50 μM) has no effect on cell viability. However, incubation of cells with LY303511 (25 μM) for 1 hour followed by 4 hours exposure to 50 ng/mL of TRAIL has a strong synergistic effect (~40% reduction in viable cells with LY303511+TRAIL versus ~15% with TRAIL alone)[2]. LY303511 is a negative control compound with respect to PI3K activity. In MIN6 insulinoma cells, Wortmannin (100 nM) has no effect on whole-cell outward K+ currents, but LY294002 and LY303511 reversibly block currents in a dose-dependent manner (IC50=9.0±0.7 μM and 64.6±9.1 μM, respectively). Kv2.1 and Kv1.4 are highly expressed in beta-cells, and in Kv2.1-transfected tsA201 cells, 50 μM LY294002 and 100 μM LY303511 reversibly inhibit currents by 99% and 41%, respectively. LY303511 blocks currents with an IC50 of 64.6±9.1 µM, with a maximal inhibition of ~90% at 500 µM (n≥5 cells at each concentration)[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Intraperitoneal administration of vehicle or LY303511 (10 mg/kg/day) is performed when tumors reach a volume of ~150 mm3, at which time 35 mice have developed a tumor. After 21 days, >15% of the mice require euthanasia because of excessive tumor growth, and these data are censored due to unreliable estimates of average tumor volume. The administration of LY303511, 10 mg/kg/day, is sufficient to inhibit PC-3 tumor growth in vivo[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Molecular Weight

342.82

Formula

C19H19ClN2O2

CAS No.
Appearance

Solid

Color

White to light yellow

SMILES

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

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Solvent & Solubility
In Vitro: 

DMSO : 25 mg/mL (72.92 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

H2O : 1 mg/mL (2.92 mM; Need ultrasonic)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.9170 mL 14.5849 mL 29.1698 mL
5 mM 0.5834 mL 2.9170 mL 5.8340 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
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Concentration
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Volume
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Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

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In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.5 mg/mL (7.29 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: ≥ 2.5 mg/mL (7.29 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation

Purity: 98.87%

References
Cell Assay
[2]

Human neuroblastoma SHEP-1 cells are maintained in DMEM supplemented with 10% fetal bovine serum and 1% Penicillin. In a typical survival assay, SHEP-1 cells (8×104 per well) plated in 24-well plates for 24 h are exposed to LY303511 (12.5, 25, and 50 μM), TRAIL (25, 50, and 100 ng/mL), and a combination of the two (1 h preincubation with LY303511 followed by TRAIL for 4 h). Cytotoxicity is determined by the crystal violet assay. After drug exposure, cells are washed with PBS and incubated for 20 min with crystal violet solution (200 μL). The excess crystal violet solution is washed away with distilled water, and the remaining crystals are dissolved with 20% acetic acid. Viability is determined by absorbance at 595 nm wavelength using an automated ELISA reader. Cell viability experiments are performed similarly with 2,000 units/mL of catalase, 4 μM JNK inhibitor SP600125, 10 μM p38 inhibitor SB202190, 20 μM MAPK/ERK kinase (MEK) inhibitor PD98059, 50 μM of caspase-8 inhibitor Z-IETD-FMK or pan-caspase inhibitor Z-VAD-FMK, or death receptor blocking antibodies (4 μg/mL anti-DR4 or 1 μg/mL anti-DR5), or in cells transfected with small interfering RNA (siRNA) for silencing JNK and ERK expression, respectively. Cells are preincubated for 1 h with LY303511 and the respective inhibitor or catalase before the addition of TRAIL. Similar sensitizing effect of LY303511 on TRAIL-induced apoptosis is carried out with SY5Y neuroblastoma, T98G glioblastoma, Jurkat leukemia, CEM myelogenous leukemia, HeLa ovarian carcinoma, and HT29 colorectal carcinoma cell lines[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[4]

Mice[4]
Human prostate adenocarcinoma (PC-3) cells (ATCC CRL-1435) are cultured in vitro before harvesting and implantation of 1×106 cells in 20% Matrigel per athymic NCR nude mouse by subcutaneous injection at the flank. Inoculated mice are subdivided into four groups of 10. Administration of vehicle or LY303511, 10 mg/kg/day, is begun (day 1) when tumors reach ~150 mm3 (n=35), and tumor volumes are measured for 30 days at the indicated time points.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
H2O / DMSO 1 mM 2.9170 mL 14.5849 mL 29.1698 mL 72.9246 mL
DMSO 5 mM 0.5834 mL 2.9170 mL 5.8340 mL 14.5849 mL
10 mM 0.2917 mL 1.4585 mL 2.9170 mL 7.2925 mL
15 mM 0.1945 mL 0.9723 mL 1.9447 mL 4.8616 mL
20 mM 0.1458 mL 0.7292 mL 1.4585 mL 3.6462 mL
25 mM 0.1167 mL 0.5834 mL 1.1668 mL 2.9170 mL
30 mM 0.0972 mL 0.4862 mL 0.9723 mL 2.4308 mL
40 mM 0.0729 mL 0.3646 mL 0.7292 mL 1.8231 mL
50 mM 0.0583 mL 0.2917 mL 0.5834 mL 1.4585 mL
60 mM 0.0486 mL 0.2431 mL 0.4862 mL 1.2154 mL

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

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    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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