ACAT1 (IC50 = 24 μM); ACAT2 (IC50 = 9.2 μM)

Prostate cancer (PCa) cells proliferate less when avasimibe (0, 0.25, 5, 10, 20, 40, and 80 μM; 1, 2 and 3 days) is administered [2]. The expression of β-catenin, Vimentin, N-cadherin, Snail, and MMP9—all of which are closely linked to the epithelial-mesenchymal transition (EMT)—is reduced by avasimibe (10 and 20 μM; 48 hours) [2]. In prostate cancer, avasimibe (10 and 20 μM) induces cell cycle arrest via the E2F-1 signaling pathway. In PCa cells, avasimibe causes a G1 phase cell cycle arrest [2]. PCa cell metastasis is inhibited by avasimibe (10 and 20 μM) [2].

For seven weeks, avasimibe (30 mg/kg intraperitoneally every other day) suppresses the development and metastasis of PCa cells in vivo. Avasimibe is minimal in toxicity and has good biocompatibility [2].

Cell Viability Assay[2]
Cell Types: PCa cells (PC-3 and DU 145)
Tested Concentrations: 0, 0.25, 5, 10, 20, 40 and 80 µM
Incubation Duration: 1, 2, and 3 days
Experimental Results: Dose dependently inhibited PC-3 and DU 145 cell viability.

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Western Blot Analysis[2]
Cell Types: PCa cells (PC-3 and DU 145)
Tested Concentrations: 10 and 20 µM
Incubation Duration: 48 hrs (hours)
Experimental Results: decreased protein levels of EMT-related proteins ( β-catenin, Vimentin, N-cadherin, Snail, MMP9 and E-cadherin).

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Cell Cycle Analysis[2]
Cell Types: PCa cells (PC-3 and DU 145)
Tested Concentrations: 10 and 20 µM
Incubation Duration: 48 hrs (hours)
Experimental Results: Induced G1 phase cycle arrest and altered the G1 phase-related protein levels in PCa cells.

Animal/Disease Models: SPF male mice (BALB/c-nude, 4 weeks old) bearing PCa cells[2]
Doses: 30 mg/kg
Route of Administration: Intraperitoneally injected for 7 weeks
Experimental Results: decreased tumor volume compared with that of the control group. Inhibited PCa growth and migration in vivo.

[1]. Taichi Ohshiro,et al. Pyripyropene A, an acyl-coenzyme A:cholesterol acyltransferase 2-selective inhibitor, attenuates hypercholesterolemia and atherosclerosis in murine models of hyperlipidemia. Arterioscler Thromb Vasc Biol. 2011 May;31(5):1108-15.
[2]. Kangping Xiong, et al. The cholesterol esterification inhibitor avasimibe suppresses tumour proliferation and metastasis via the E2F-1 signalling pathway in prostate cancer.Cancer Cell Int. 2021 Aug 30;21(1):461.

Avasimibe is an orally bioavailable inhibitor of acyl-Coenzyme A:cholesterol acyltransferase (ACAT) that prevents cholesterol deposition in the arterial wall. Research was discontinued due to difficulties in assaying the effects of avasimibe on preventing plaque formation and due to its ability to increase the activity of Cytochrome P450 3A4, thus increasing the removal of other drugs from the body.

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Background: New effective drugs for prostate cancer (PCa) treatment are urgently needed. Avasimibe was recently identified as a promising drug for anticancer therapies. The main purpose of this study was to explore the effects and the underlying mechanisms of avasimibe in prostate cancer.
Methods: In this study, MTT and clonogenic survival assays were performed to detect cell proliferation after avasimibe treatment. The effect of avasimibe on cell migration was measured by wound healing and transwell migration assays. Cell cycle distribution and apoptosis were detected by flow cytometry. Immunofluorescence staining and western blot analysis were used to detect the expression of cell cycle-related proteins and epithelial-mesenchymal transition (EMT)-related proteins. In vivo, the antitumour effects of avasimibe were evaluated using a xenograft model and pulmonary metastasis model.
Results: The study found that avasimibe suppresses tumour growth and triggers G1 phase arrest. Moreover, the expression of the cell cycle-related proteins CDK2/4/6, Cyclin D1 and Cyclin A1 + A2 was significantly increased and p21 expression was decreased after avasimibe treatment. The migration of PCa cells was attenuated after treatment with avasimibe, followed by the downregulation of the expression of the EMT-related proteins N-cadherin, β-catenin, vimentin, Snail and MMP9 and upregulation of E-cadherin expression. Moreover, E2F-1 was elevated after treatment with avasimibe. After knockdown of E2F-1 expression, the inhibition of cell proliferation and migration caused by avasimibe was significantly recovered. The results of the xenograft model showed that avasimibe suppressed tumour growth in vivo. Immunofluorescence staining revealed lower levels of Ki67 and higher levels of E2F-1 in tumour tissues of the avasimibe group than those of the control group. A pulmonary metastasis model also confirmed the inhibition of PCa metastasis by avasimibe. The number of lung metastatic foci in the avasimibe group was significantly decreased compared with that in the control group.
Conclusions: Our results suggest that avasimibe can suppress tumour proliferation and metastasis via the E2F-1 signalling pathway. These findings demonstrate the potential of avasimibe as a new effective drug for PCa treatment.

C29H43NO4S

501.72

501.29129

C, 69.42; H, 8.64; N, 2.79; O, 12.76; S, 6.39

166518-60-1

166518-61-2 (sodium);166518-60-1 (free form);

166558

Typically exists as white to off-white solids at room temperature

1.1±0.1 g/cm3

178-180°C

1.529

9.34

80.85

c1(C(C)C)cc(cc(c1CC(NS(Oc1c(cccc1C(C)C)C(C)C)(=O)=O)=O)C(C)C)C(C)C

PTQXTEKSNBVPQJ-UHFFFAOYSA-N

InChI=1S/C29H43NO4S/c1-17(2)22-14-25(20(7)8)27(26(15-22)21(9)10)16-28(31)30-35(32,33)34-29-23(18(3)4)12-11-13-24(29)19(5)6/h11-15,17-21H,16H2,1-10H3,(H,30,31)

((2,4,6-Tris(1-methylethyl)phenyl)acetyl)sulfamic acid 2,6-bis(1-methylethyl)phenyl ester

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)

Solubility in Formulation 1: 7.5 mg/mL (14.95 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 75.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 7.5 mg/mL (14.95 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 75.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: 7.5 mg/mL (14.95 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 75.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 2% DMSO+corn oil: 5mg/mL

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