SL-176 effectively inhibited the phosphatase activity of mouse PPM1D with an IC50 value of 112 nM[1]. SL-176 (0-15 μM, 8 days) inhibited the formation of lipid droplets in 3T3-L1 cells in a dose-dependent manner. At a concentration of 15 μM, SL-176 reduced the relative lipid content in cells to 32% of the control group, reduced the average size of lipid droplets in cells from 2.95 μm to 1.71 μm, and shifted the lipid droplet size distribution towards smaller sizes[1]. SL-176 (10 μM, 8 days) reduced the mRNA expression of PPARγ, C/EBPα and GLUT4 in 3T3-L1 cells, but had no effect on the mRNA expression of C/EBPβ[1]. SL-176 (0-15 μM, 8 days) reduced the protein expression of PPARγ1, PPARγ2 and C/EBPα in 3T3-L1 cells in a dose-dependent manner, but had no effect on the protein expression of C/EBPβ [1]. SL-176 potently and specifically inhibited the phosphatase activity of recombinant His-PPM1D (1-420) in a non-competitive manner, with an IC50 of 110 nM [2]. SL-176 (treatment for 3 days) potently inhibited the proliferation of MCF-7 breast cancer cells overexpressing PPM1D, with an IC50 of 7.4 μM [2]. SL-176 (0-20 μM) selectively inhibited the proliferation of p53-deficient, PPM1D-overexpressing H1299 (PMD-9) cells, with higher inhibitory efficacy than that on parental H1299 cells with normal PPM1D expression [2]. SL-176 activates the p53 pathway in MCF-7 breast cancer cells by enhancing phosphorylation of p53 Ser15, and induces cell cycle arrest and apoptosis in these cells during the G2/M phase [2]. SL-176 (11 μM; 72 h) in combination with GSK-J4 synergistically reduces the viability of IMR-32 and SK-N-AS neuroblastoma cells [3]. SL-176 (72 h) in combination with GSK-J4 showed 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]. SL-176 (7.5–15 μM; 6 days) in combination with GSK-J4 reduced the spheroid volume in 3D neuroblastoma spheroid models of IMR-32 and SK-N-AS in a dose-dependent manner and induced apoptosis[3]. SL-176 (3–5 μM; 48–72 hours) in combination with GSK-J4 activated downstream targets of WIP1, upregulated the expression of p53 pathway genes, and increased the levels of apoptosis markers in IMR-32, SK-N-AS, and SK-N-BE (2) neuroblastoma cells[3].

The combined use of SL-176 (10 μM; added to water; continuous exposure; 72 hours) and 1 μM GSK-J4 significantly reduced the growth of zebrafish xenograft neuroblastoma, with the mean percentage change in tumor size being significantly lower than that of the vector control (P = 0.0096) [3].

Real-time quantitative PCR[1]
Cell Types: 3T3-L1 preadipocytes in differentiation
Tested Concentrations: 10 μM
Incubation Duration: 8 days (during adipocyte differentiation)
Experimental Results: mRNA expression of PPARγ and C/EBPα was reduced to half or less of that in the control group. There was no significant effect on the mRNA expression of C/EBPβ. The mRNA expression of the adipocyte marker GLUT4 was reduced.

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Western Blot Analysis [1]
Cell Types: 3T3-L1 preadipocytes in differentiation
Tested Concentrations: 5, 10, 15 μM
Incubation Duration: 8 days (during adipocyte differentiation)
Experimental Results: PPARγ1, PPARγ2 and C/EBPα protein expression decreased in a dose-dependent manner: 5 μM reduced PPARγ1/2 to 37/38% of the control group, 10 μM reduced PPARγ1/2 to 38/9% of the control group, and 15 μM reduced PPARγ1/2 to 9% of the control group/PPARγ2 was undetectable; 5 μM concentration reduced C/EBPα level to 81% of the control group, 10 μM concentration reduced C/EBPα level to 83% of the control group, and 15 μM concentration reduced C/EBPα level to 52% of the control group. It had no significant effect on C/EBPβ protein expression.

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Cell viability assay [3]
Cell Types: IMR-32, SK-N-AS neuroblastoma cell lines
Tested Concentrations: 11 μM
Incubation Duration: 72 hours
Experimental Results: When used in combination with GSK-J4 in IMR-32 cells, the ΔDSS was 18.9. When used in combination with GSK-J4 in SK-N-AS cells, the ΔDSS was 5.7. In IMR-32 cells, the dose-response curve of GSK-J4 shifted to the left by more than an order of magnitude. In SK-N-AS cells, the dose-response curve of GSK-J4 shifted to the left, but incomplete inhibition was observed.

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Apoptosis analysis [3]
Cell Types: IMR-32, SK-N-AS neuroblastoma cells co-cultured with nHDF cells
Tested Concentrations: 7.5-15 μM
Incubation Duration: 6 days Experimental
Experimental Results: When used in combination with GSK-J4, the volume of IMR-32 cell spheroids decreased in a dose-dependent manner, and the SYTOX Green fluorescence intensity (cell death) increased in a dose-dependent manner; there was no significant effect when used alone. When used in combination with GSK-J4, the volume of SK-N-AS cell spheroids decreased in a dose-dependent manner, and cell death increased in a dose-dependent manner; when used alone, the volume of SK-N-AS cell spheroids was reduced only at a concentration of 15 μM. When used in combination with GSK-J4, staining for cleavage caspase-3 (apoptosis) and p21 (WIP1 inhibition) was enhanced in IMR-32 spheroids. Cleavage caspase-3 was increased in SK-N-AS spheroid tumor cells, either alone or in combination with GSK-J4.

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Animal/Disease Models:Embryo (48 hours post-fertilization, non-feeding period) [3]
Doses: 10 μM (used in combination with 1 μM GSK-J4)
Route of Administration: Added to water; continuous exposure; 72 hours
Experimental Results: Compared with the solvent control group, tumor growth was significantly reduced, and the mean percentage change in tumor size was significantly lower in the solvent group. When used alone, no significant change in tumor growth was observed compared with the solvent control group.

[1]. Inhibition of lipid droplet formation by Ser/Thr protein phosphatase PPM1D inhibitor, SL-176. PLoS One. 2019;14(2):e0212682. Published 2019 Feb 27.

[2]. Novel inhibitors targeting PPM1D phosphatase potently suppress cancer cell proliferation. Bioorg Med Chem. 2015;23(19):6246-6249.

[3]. Targeted inhibition of WIP1 and histone H3K27 demethylase activity synergistically suppresses neuroblastoma growth. Cell Death Dis. 2025;16(1):318. Published 2025 Apr 19.

C24H48O4SI2

456.81

1809556-48-6

White to off-white solid

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]

2934.99.9001

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)

DMSO : ~100 mg/mL (~218.91 mM; with sonication)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.47 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you canAdd 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well.

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