1. Autophagy
  2. Autophagy
  3. AC-73

AC-73 is a first specific, orally active inhibitor of cluster of differentiation 147 (CD147), which specifically disrupts CD147 dimerization, thereby mainly suppressing the CD147/ERK1/2/STAT3/MMP-2 pathways. AC-73 inhibits the motility and invasion of hepatocellular carcinoma cells. AC-73 is also an anti-proliferative agent and an inducer of autophagy in leukemic cells.

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AC-73 Chemical Structure

AC-73 Chemical Structure

CAS No. : 775294-71-8

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Customer Review

Based on 4 publication(s) in Google Scholar

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Description

AC-73 is a first specific, orally active inhibitor of cluster of differentiation 147 (CD147), which specifically disrupts CD147 dimerization, thereby mainly suppressing the CD147/ERK1/2/STAT3/MMP-2 pathways. AC-73 inhibits the motility and invasion of hepatocellular carcinoma cells[1]. AC-73 is also an anti-proliferative agent and an inducer of autophagy in leukemic cells[2].

IC50 & Target

CD147[1]

In Vitro

AC-73 (5-10 μM; 24 hours; SMMC-7721 and Huh-7 cells) treatment significantly decreases the migration ability of SMMC-7721 and Huh-7 cells in a dose-dependent manner and decreases the invasion of two HCC cells in a dose-dependent manner at 24 hours. AC-73 treatment reduces HCC metastases. There are no obvious effects on cell viability when two HCC cells are treated with AC-73 at a maximum concentration of 20 μM. The possible binding sites of AC-73 on CD147 included Glu64 and Glu73 in the N-terminal IgC2 domain, which two residues are located in the dimer interface of CD147[1].
AC-73 (5-10 μM; 24 hours; SMMC-7721 cells) treatment could significantly inhibit both MMP-2 and MMP-9 mRNA expression at the concentration of 10 μM, especially MMP-2, but no obvious effect on MMP-1, MMP-3, MMP-7, MMP-11 nor MMP-13. AC-73 could dose dependently reduce the expression of MMP-2 mRNA level and secretion of the protein level using RT-qPCR analysis and gelatin zymography experiments[1].
AC-73 (5-20 μM; 6 hours; SMMC-7721 cells) treatment dose-dependently suppresses the phosphorylation of ERK1/2 and STAT3[1].

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

RT-PCR[1]

Cell Line: SMMC-7721 cells
Concentration: 5 μM or 10 μM
Incubation Time: 24 hours
Result: Significantly inhibited both MMP-2 and MMP-9 mRNA expression at the concentration of 10 μM. Dose dependently reduced the expression of MMP-2 mRNA level and secretion of the protein level using RT-qPCR analysis and gelatin zymography experiments.

Western Blot Analysis[1]

Cell Line: SMMC-7721 cells
Concentration: 5 μM, 10 μM or 20 μM
Incubation Time: 6 hours
Result: The phosphorylation of ERK1/2 and STAT3 was dose-dependently suppressed.
In Vivo

AC-73 (25-50 mg/kg; for 4 weeks; Male BALB/c nu/nu mice) treatment significantly decreases the incidence of metastatic foci in nude mice. AC-73 inhibits the phosphorylation of ERK1/2 and STAT3 in a dose-dependent manner. MMP-2 is also reduced by AC-73. AC-73 could not inhibit tumor cell proliferation in vivo[1].

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

Animal Model: Male BALB/c nu/nu mice (4-6 weeks) with SMMC-7721 cells[1]
Dosage: 25 mg/kg, 50 mg/kg
Administration: Injected; daily; for 3 weeks
Result: Significantly decreased the incidence of metastatic foci in nude mice. Inhibited the phosphorylation of ERK1/2 and STAT3 in a dose-dependent manner. MMP-2 was also reduced.
Molecular Weight

319.40

Formula

C21H21NO2

CAS No.
Appearance

Solid

Color

White to off-white

SMILES

OC(CNCC1=CC=C(C2=CC=CC=C2)C=C1)C3=CC=CC(O)=C3

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
Solvent & Solubility
In Vitro: 

DMSO : ≥ 250 mg/mL (782.72 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 3.1309 mL 15.6544 mL 31.3087 mL
5 mM 0.6262 mL 3.1309 mL 6.2617 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

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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: ≥ 2.08 mg/mL (6.51 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 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: ≥ 2.08 mg/mL (6.51 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 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
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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).
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: 99.89%

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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 3.1309 mL 15.6544 mL 31.3087 mL 78.2718 mL
5 mM 0.6262 mL 3.1309 mL 6.2617 mL 15.6544 mL
10 mM 0.3131 mL 1.5654 mL 3.1309 mL 7.8272 mL
15 mM 0.2087 mL 1.0436 mL 2.0872 mL 5.2181 mL
20 mM 0.1565 mL 0.7827 mL 1.5654 mL 3.9136 mL
25 mM 0.1252 mL 0.6262 mL 1.2523 mL 3.1309 mL
30 mM 0.1044 mL 0.5218 mL 1.0436 mL 2.6091 mL
40 mM 0.0783 mL 0.3914 mL 0.7827 mL 1.9568 mL
50 mM 0.0626 mL 0.3131 mL 0.6262 mL 1.5654 mL
60 mM 0.0522 mL 0.2609 mL 0.5218 mL 1.3045 mL
80 mM 0.0391 mL 0.1957 mL 0.3914 mL 0.9784 mL
100 mM 0.0313 mL 0.1565 mL 0.3131 mL 0.7827 mL
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  • 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.

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AC-73
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