2. Anti-infection PI3K/Akt/mTOR
  3. Akt Influenza Virus
  4. Tilorone

Tilorone is an orally active antiviral agent and interferon inducer that also has potential antineoplastic, immunomodulatory, and metabolic modulating effects. Tilorone induces an abnormally delayed interferon response and primarily stimulates interferon production in lymphoid tissue. Thus, Tilorone exerts antiviral effects and can be used as a chemotherapeutic agent. Tilorone has the potential to inhibit type 2 diabetes by increasing glucose uptake in vivo and in skeletal muscle cells by enhancing Akt2/AS160 signaling and glucose transporter levels.

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Tilorone Chemical Structure

Tilorone Chemical Structure

CAS No. : 27591-97-5

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Based on 2 publication(s) in Google Scholar

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  • Biological Activity

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Description

Tilorone is an orally active antiviral agent and interferon inducer that also has potential antineoplastic, immunomodulatory, and metabolic modulating effects. Tilorone induces an abnormally delayed interferon response and primarily stimulates interferon production in lymphoid tissue. Thus, Tilorone exerts antiviral effects and can be used as a chemotherapeutic agent. Tilorone has the potential to inhibit type 2 diabetes by increasing glucose uptake in vivo and in skeletal muscle cells by enhancing Akt2/AS160 signaling and glucose transporter levels[1][2][3][4][5].

Cellular Effect
Cell Line Type Value Description References
HeLa IC50
1.14 μM
Compound: Tilorone
Antiviral activity against Ebolavirus infected in human HeLa cells assessed as reduction in viral replication incubated for 48 hrs by luminescence based assay
Antiviral activity against Ebolavirus infected in human HeLa cells assessed as reduction in viral replication incubated for 48 hrs by luminescence based assay
[PMID: 32832035]
Oocyte EC50
2.5 μM
Compound: 1
Agonist activity at human recombinant alpha7 nAChR expressed in xenopus oocytes by patch clamp assay
Agonist activity at human recombinant alpha7 nAChR expressed in xenopus oocytes by patch clamp assay
[PMID: 22281189]
Vero CC50
19.67 μM
Compound: Tilorone
Cell viability measured by CellTiter-Glo assay in Vero cells at MOI 0.05 after 72hr
Cell viability measured by CellTiter-Glo assay in Vero cells at MOI 0.05 after 72hr
10.1101/2020.03.20.999730
Vero IC50
4.09 μM
Compound: Tilorone
Antiviral activity against SARS-CoV-2 (viral titer) measured by plaque assay in Vero cells at MOI 0.0125 after 24 hr
Antiviral activity against SARS-CoV-2 (viral titer) measured by plaque assay in Vero cells at MOI 0.0125 after 24 hr
10.1101/2020.03.20.999730
In Vitro

Tilorone (0.8-500 μg/mL; 2 d) induces insignificant interferon production in peritoneal macrophages and lymphocytes[1].
Tilorone has 52% of human plasma proteins Binding rate, excellent plasma stability, mouse liver microsomal half-life of 48 minutes[2].
Tilorone (20, 35 nM; 40 h) increases bone morphology in myoblasts The expression of BMP and Smad4[3].
Tilorone (20, 35 nM; 40 h) can also increase the expression of GLUT and glucose uptake in C2C12 cells[3] < /sup>.
Tilorone (3 μM-20 μM; 72 h) can also selectively target PC3 cells with low CDK5 activity[4] .

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

Tilorone Related Antibodies

Western Blot Analysis[3]

Cell Line: Myoblasts
Concentration: 20 nM, 35 nM
Incubation Time: 40 h
Result: Increased the phosphorylation of Smad1/5/8, indicating the enhancement of BMP signaling.
In Vivo

Tilorone (50-250 mg/kg; po; single dose) can induce a delayed but not prolonged interferon response; and affects circulating interferon levels in a dose-dependent manner[1].
The maximum tolerated single dose of Tilorone in mice is 100 mg/kg; pharmacokinetic results of Tilorone (2, 10 mg/kg; ip) in mice indicate that Tilorone has a high absorption rate and is The half-life in mice is 18 hours, but exposure in male mice is higher[2].
Tilorone (25-50 mg/kg; ip; once daily for 8 days ) protects 90% of Ebola virus-infected mice from lethal challenge[2].
Tilorone (25 mg/kg; iv; single dose) enhances immunity in small Uptake of the radiolabeled glucose analog 18F-fluoro-2-deoxyglucose in rats[3].

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

Animal Model: 6-week-old female mouse[1]
Dosage: 250 mg/kg
Administration: po; single dose
Result: Resulted in correspondingly lower levels of circulating interferon, although moderately high levels were obtained (2,500 units/ml) with as little as 50 mg/kg. Interferon production was not detected in the upper gastrointestinal tract.
Animal Model: Ebola virus disease (EVD) infected mouse model[2]
Dosage: 25 mg/kg, 30 mg/kg, 50 mg/kg
Administration: ip; once daily for 8 days
Result: Showed was fully protective effect at 30 mg/kg, starting 2 or 24 h postchallenge and continuing through day 7 postinfection.
Animal Model: C57BL/6 mouse[3]
Dosage: 25 mg/kg
Administration: IV; in 100 μL saline via the lateral tail vein
Result: Significant increased in the SUV mean of skeletal muscle, adipose tissue, and liver.
Molecular Weight

410.55

Formula

C25H34N2O3
CAS No.
Appearance

Solid

Color

Orange to red

SMILES

O=C1C2=C(C3=C1C=C(OCCN(CC)CC)C=C3)C=CC(OCCN(CC)CC)=C2
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

-20°C, protect from light

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

Solvent & Solubility
In Vitro: 

DMSO : 25 mg/mL (60.89 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.4358 mL 12.1788 mL 24.3576 mL
5 mM 0.4872 mL 2.4358 mL 4.8715 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 (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

  • Molarity Calculator

  • Dilution Calculator

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

Mass
=
Concentration
×
Volume
×
Molecular Weight *

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

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

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 (6.09 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 (6.09 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 (protect from light)

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
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 (protect from light). 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
DMSO 1 mM 2.4358 mL 12.1788 mL 24.3576 mL 60.8939 mL
5 mM 0.4872 mL 2.4358 mL 4.8715 mL 12.1788 mL
10 mM 0.2436 mL 1.2179 mL 2.4358 mL 6.0894 mL
15 mM 0.1624 mL 0.8119 mL 1.6238 mL 4.0596 mL
20 mM 0.1218 mL 0.6089 mL 1.2179 mL 3.0447 mL
25 mM 0.0974 mL 0.4872 mL 0.9743 mL 2.4358 mL
30 mM 0.0812 mL 0.4060 mL 0.8119 mL 2.0298 mL
40 mM 0.0609 mL 0.3045 mL 0.6089 mL 1.5223 mL
50 mM 0.0487 mL 0.2436 mL 0.4872 mL 1.2179 mL
60 mM 0.0406 mL 0.2030 mL 0.4060 mL 1.0149 mL
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Tilorone Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    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.

Keywords:

Tilorone27591-97-5AktInfluenza VirusPKBProtein kinase BInhibitorinhibitorinhibit

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