2. Metabolic Enzyme/Protease Apoptosis
  3. Phosphatase Apoptosis MDM-2/p53 Caspase
  4. SL-176

SL-176 is a PPM1D (Wip1) inhibitor. SL-176 inhibits lipid droplet formation, downregulates the mRNA and protein expression of PPARγ and C/EBPα, and blocks adipocyte differentiation. SL-176 induces G2/M cell cycle arrest, apoptosis and inhibits cell proliferation in breast cancer cells overexpressing PPM1D, and activates components of the p53 pathway. SL-176 suppresses tumor growth in a zebrafish model of neuroblastoma. SL-176 is applicable to research related to obesity, breast cancer and neuroblastoma.

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SL-176

SL-176 Chemical Structure

CAS No. : 1809556-48-6

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Based on 1 publication(s) in Google Scholar

SL-176 Related Antibodies

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Description

SL-176 is a PPM1D (Wip1) inhibitor. SL-176 inhibits lipid droplet formation, downregulates the mRNA and protein expression of PPARγ and C/EBPα, and blocks adipocyte differentiation. SL-176 induces G2/M cell cycle arrest, apoptosis and inhibits cell proliferation in breast cancer cells overexpressing PPM1D, and activates components of the p53 pathway. SL-176 suppresses tumor growth in a zebrafish model of neuroblastoma. SL-176 is applicable to research related to obesity, breast cancer and neuroblastoma[1][2][3].

Cellular Effect
Cell Line Type Value Description References
MCF7 IC50
7.4 μM
Compound: SL-176
Inhibition of cell proliferation of human MCF7 cells incubated for 24 hrs
Inhibition of cell proliferation of human MCF7 cells incubated for 24 hrs
[PMID: 26358280]
In Vitro

SL-176 potently inhibits the phosphatase activity of mouse PPM1D, with an IC50 of 112 nM[1].
SL-176 (0-15 μM, 8 days) inhibits lipid droplet formation in 3T3-L1 cells in a dose-dependent manner. At the concentration of 15 μM, it reduces the relative lipid content to 32% of that in the control group, decreases the average lipid droplet size in cells from 2.95 μm to 1.71 μm, and shifts the lipid droplet size distribution toward smaller sizes[1].
SL-176 (10 μM, 8 days) reduces the mRNA expression of PPARγ, C/EBPα and GLUT4 in 3T3-L1 cells, but has no effect on the mRNA expression of C/EBPβ[1].
SL-176 (0-15 μM, 8 days) reduces the protein expression of PPARγ1, PPARγ2 and C/EBPα in 3T3-L1 cells in a dose-dependent manner, but has no effect on the protein expression of C/EBPβ[1].
SL-176 potently and specifically inhibits the phosphatase activity of recombinant His-PPM1D (1-420) in a non-competitive manner, with an IC50 of 110 nM[2].
SL-176 (for 3 days) potently inhibits the proliferation of MCF-7 breast cancer cells overexpressing PPM1D, with an IC50 of 7.4 μM[2].
SL-176 (0-20 μM) exerts a selective inhibitory effect on the proliferation of p53-deficient, PPM1D-overexpressing H1299 (PMD-9) cells, with greater potency than that observed in parental H1299 cells with normal PPM1D expression[2].
SL-176 activates the p53 pathway in MCF-7 breast cancer cells by enhancing p53 Ser15 phosphorylation, and induces G2/M cell cycle arrest and apoptosis in these cells[2].
SL-176 (11 μM; 72 h) synergistically reduces the viability of IMR-32 and SK-N-AS neuroblastoma cells in combination with GSK-J4 (HY-15648B)[3].
Combination treatment with SL-176 (72 h) and GSK-J4 induces additive to synergistic cytotoxicity in all tested neuroblastoma cell lines (IMR-32, SK-N-SH, SK-N-AS, SK-N-BE (2), SK-N-FI, SK-N-DZ, Kelly, CHLA-20 cells)[3].
Combination treatment with SL-176 (7.5-15 μM; 6 days) and GSK-J4 reduces spheroid volume in a dose-dependent manner and induces apoptosis in 3D neuroblastoma spheroid models of IMR-32 and SK-N-AS[3].
Combination treatment with SL-176 (3-5 μM; 48-72 h) and GSK-J4 activates downstream targets of WIP1, upregulates the expression of p53 pathway genes, and increases the levels of apoptotic markers in IMR-32, SK-N-AS and SK-N-BE (2) neuroblastoma cells[3].

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

SL-176 Related Antibodies

Real Time qPCR[1]

Cell Line: Differentiating 3T3-L1 preadipocytes
Concentration: 10 μM
Incubation Time: 8 days (during adipocyte differentiation)
Result: Reduced mRNA expression of PPARγ and C/EBPα to half or less than half of control levels.
Had no significant effect on C/EBPβ mRNA expression.
Reduced mRNA expression of the adipocyte marker GLUT4.

Western Blot Analysis[1]

Cell Line: Differentiating 3T3-L1 preadipocytes
Concentration: 5, 10, 15 μM
Incubation Time: 8 days (during adipocyte differentiation)
Result: Reduced protein expression of PPARγ1, PPARγ2, and C/EBPα in a dose-dependent manner: 5 μM reduced PPARγ1/2 to 37/38% of control, 10 μM reduced PPARγ1/2 to 38/9% of control, 15 μM reduced PPARγ1/2 to 9/undetectable (PPARγ2) of control; 5 μM reduced C/EBPα to 81% of control, 10 μM reduced C/EBPα to 83% of control, 15 μM reduced C/EBPα to 52% of control.
Had no significant effect on C/EBPβ protein expression.

Cell Viability Assay[3]

Cell Line: IMR-32, SK-N-AS neuroblastoma cell lines
Concentration: 11 μM
Incubation Time: 72 h
Result: Yielded a ΔDSS of 18.9 when combined with GSK-J4 in IMR-32 cells.
Yielded a ΔDSS of 5.7 when combined with GSK-J4 in SK-N-AS cells.
Shifted the GSK-J4 dose-response curve left by more than one order of magnitude in IMR-32 cells.
Shifted the GSK-J4 dose-response curve left in SK-N-AS cells with incomplete inhibition observed.

Apoptosis Analysis[3]

Cell Line: IMR-32, SK-N-AS neuroblastoma cells co-cultured with nHDF cells
Concentration: 7.5-15 μM
Incubation Time: 6 days
Result: Reduced IMR-32 spheroid size and increased SYTOX Green fluorescence (cell death) in a dose-dependent manner when combined with GSK-J4, with no significant effect as a single agent.
Reduced SK-N-AS spheroid size and increased cell death in a dose-dependent manner when combined with GSK-J4; reduced SK-N-AS spheroid size only at 15 μM as a single agent.
Increased cleaved caspase-3 (apoptosis) and p21 (WIP1 inhibition) staining in IMR-32 spheroids when combined with GSK-J4.
Increased cleaved caspase-3 in SK-N-AS spheroid tumor cells when used as a single agent or combined with GSK-J4.
In Vivo

SL-176 (10 μM; added to water; continuous exposure; 72 hours) in combination with 1 μM GSK-J4 significantly reduces neuroblastoma tumor growth in zebrafish xenografts, with a mean percent change in tumor size that is significantly lower than vehicle control (P = 0.0096)[3].

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

Animal Model: embryos (48 hours post-fertilization, non-feeding stage)[3]
Dosage: 10 μM (in combination with 1 μM GSK-J4)
Administration: added to water; continuous exposure; 72 hours
Result: Resulted in a significant decrease in tumor growth compared to vehicle control, with mean percent change in tumor size significantly lower than vehicle group.
Showed no significant change in tumor growth when used alone compared to vehicle control.
Molecular Weight

456.81

Formula

C24H48O4Si2
CAS No.
Appearance

Solid

Color

White to off-white

SMILES

CC[Si](CC)(CC)O[C@@H]1CCC[C@@]2([H])[C@@](C(O)=O)(C)C[C@@H](O[Si](C)(C(C)(C)C)C)C[C@@]21[H]
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 100 mg/mL (218.91 mM; Need ultrasonic; 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 2.1891 mL 10.9455 mL 21.8909 mL
5 mM 0.4378 mL 2.1891 mL 4.3782 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. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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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    90% Corn Oil

    Solubility: ≥ 2.5 mg/mL (5.47 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
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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
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. 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 2.1891 mL 10.9455 mL 21.8909 mL 54.7273 mL
5 mM 0.4378 mL 2.1891 mL 4.3782 mL 10.9455 mL
10 mM 0.2189 mL 1.0945 mL 2.1891 mL 5.4727 mL
15 mM 0.1459 mL 0.7297 mL 1.4594 mL 3.6485 mL
20 mM 0.1095 mL 0.5473 mL 1.0945 mL 2.7364 mL
25 mM 0.0876 mL 0.4378 mL 0.8756 mL 2.1891 mL
30 mM 0.0730 mL 0.3648 mL 0.7297 mL 1.8242 mL
40 mM 0.0547 mL 0.2736 mL 0.5473 mL 1.3682 mL
50 mM 0.0438 mL 0.2189 mL 0.4378 mL 1.0945 mL
60 mM 0.0365 mL 0.1824 mL 0.3648 mL 0.9121 mL
80 mM 0.0274 mL 0.1368 mL 0.2736 mL 0.6841 mL
100 mM 0.0219 mL 0.1095 mL 0.2189 mL 0.5473 mL
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SL-176 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:

SL-1761809556-48-6SL176SL 176PhosphataseApoptosisMDM-2/p53CaspasePPM1D Inhibitor3T3-L1 cellsMCF-7 breast cancer cellsIMR-32 cellsSK-N-SH cellsSK-N-AS cellsSK-N-BE(2) cellsSK-N-FI cellsSK-N-DZ cellsKelly cellsCHLA-20 cellsobesitybreast cancerneuroblastomaZebrafishInhibitorinhibitorinhibit

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