Pipoxolan 

Pipoxolan is an orally active smooth muscle relaxant, anti-inflammatory agent and anticancer agent. Pipoxolan modulates PI3K/AKT signaling pathways, and reduces the levels of Ras/MEK/p-ERK, MMP-2 and MMP-9. Pipoxolan inhibits pro-inflammatory transcription factor pathways, activates Nrf2/HO-1, and suppresses the production of pro-inflammatory mediators. Pipoxolan induces ROS generation, endogenous mitochondrial Apoptosis, and G₀/G₁ cell cycle arrest. Pipoxolan reduces cerebral infarction size and inhibits intimal hyperplasia. Pipoxolan can be used in research related to cerebral ischemia, intimal hyperplasia, oral squamous cell carcinoma, leukemia and lung cancer^{[1][2][3][4][5]}.

Pipoxolan (5-15 µM; 24, 48, 72 hr) potently inhibits PDGF-BB-stimulated migration of A7r5 vascular smooth muscle cells in a dose-dependent manner over 24, 48, and 72 hours^[1].
Pipoxolan (5-15 µM; 48 hr pre-treatment; 8 hr migration period) inhibits PDGF-BB-stimulated migration of A7r5 vascular smooth muscle cells in a transwell assay, with 76.5% inhibition at the highest concentration^[1].
Pipoxolan (5-15 µM; 48 hr) downregulates Ras, MEK, p-ERK, MMP-2, and MMP-9 protein levels in PDGF-BB-stimulated A7r5 vascular smooth muscle cells, with the greatest reduction in p-ERK (75%) at 15 µM^[1].
Pipoxolan (1.6-100 μg/mL; 24 h) is cytotoxic to human TW206, HSC-3, and Cal-27 cells in vitro, with IC₅₀ values of 13.13 μg/mL, 42.28 μg/mL, and 52.69 μg/mL respectively, and TW206 and HSC-3 cells are more sensitive than Cal-27 cells^[2].
Pipoxolan (20 μg/mL; 2-6 h) induces apoptosis in human TW206 OSCC cells in a time-dependent manner, with detectable apoptosis at 2 h and maximal levels at 6 h of treatment with 20 μg/mL pipoxolan^[2].
Pipoxolan (4-32 μM; 1 h pretreatment; 24 h LPS incubation) exhibits no significant cytotoxicity in LPS-stimulated RAW 264.7 murine macrophage cells^[3].
Pipoxolan (4-32 μM; 1 h pretreatment; 24 h LPS incubation) dose-dependently inhibits LPS-induced nitrite production in RAW 264.7 murine macrophage cells, with 68.24% inhibition at 32 μM^[3].
Pipoxolan (4-32 μM; 1 h pretreatment; 24 h LPS incubation) dose-dependently inhibits LPS-induced production of PGE₂, TNF-α, and IL-6 in RAW 264.7 murine macrophage cells, with maximum inhibition of 90.73% (PGE₂), 90% (TNF-α), and 95.27% (IL-6) at 32 μM^[3].
Pipoxolan (1.6-50 μg/mL; 24 h) potently inhibits proliferation of human leukaemia HL-60 cells with an IC₅₀ of 6.25 μg/mL, U937 cells with an IC₅₀ of 12.5 μg/mL, and K562 cells with an IC₅₀ of 25 μg/mL after 24 h, while showing no cytotoxicity against normal human PBMC at concentrations up to 50 μg/mL^[4].
Pipoxolan (1.6-25 μg/mL; 2-48 h) arrests human leukaemia HL-60 cells in the G₀/G₁ phase in a time-dependent manner, reaching 62.0% at 48 h with 6.25 μg/mL, and induces dose-dependent sub-G₁ apoptotic cell accumulation after 24 h^[4].
Pipoxolan (3.2-25 μg/mL; 15 min-24 h) induces rapid, time- and concentration-dependent intracellular ROS generation in human leukaemia HL-60 cells, which is critical for its apoptotic activity, as NAC pretreatment blocks both ROS production and apoptosis^[4].
Pipoxolan (2-10 μg/mL; 24 h) significantly inhibits proliferation of CL1-5 lung adenocarcinoma cells at 5 and 10 μg/mL after 24 h of incubation^[5].
Pipoxolan (2-10 μg/mL; 24 h) does not induce apoptosis in CL1-5 or CL1-0 lung adenocarcinoma cells at concentrations of 2, 5, or 10 μg/mL after 24 h of incubation^[5].

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

Pipoxolan (10-30 mg/kg; p.o.; single dose 1 hour pre-ischemia) dose-dependently reduces cerebral ischemia-reperfusion injury in male Sprague-Dawley rats, with 30 mg/kg (p.o.) achieving a 73.43% reduction in cerebral infarction area and 63.44% reduction in cleaved caspase-3-positive cells^[1].
Pipoxolan (10-30 mg/kg; p.o.; daily; 28 days starting on the day of ligation) dose-dependently reduces carotid artery ligation-induced intimal hyperplasia in male ICR mice, with 30 mg/kg (p.o., daily for 28 days) achieving a 47.20% reduction in the I/M ratio and 62.40% inhibition of PCNA-positive cells^[1].

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

351.45

C₂₂H₂₅NO₃

23744-24-3

O=C1OC(OC1(C=2C=CC=CC2)C=3C=CC=CC3)CCN4CCCCC4

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Chen YF, et al. Pipoxolan ameliorates cerebral ischemia via inhibition of neuronal apoptosis and intimal hyperplasia through attenuation of VSMC migration and modulation of matrix metalloproteinase-2/9 and Ras/MEK/ERK signaling pathways. PLoS One. 2013;8(9):e75654. Published 2013 Sep 24.

  [2]. Chou PY, et al. Pipoxolan Exhibits Antitumor Activity Toward Oral Squamous Cell Carcinoma Through Reactive Oxygen Species-mediated Apoptosis. Anticancer Res. 2017;37(11):6391-6400.  [Content Brief]

  [3]. Lin YH, et al. Pipoxolan suppresses the inflammatory factors of NF-κB, AP-1, and STATs, but activates the antioxidative factor Nrf2 in LPS-stimulated RAW 264.7 murine macrophage cells. Environ Toxicol. 2020;35(12):1352-1363.

  [4]. Sheu MJ, et al. Pipoxolan inhibits proliferation of HL-60 human leukaemia cancer cells by arresting the cell cycle at the G0/G1 phase. Clin Exp Pharmacol Physiol. 2010;37(5-6):605-612.  [Content Brief]

  [5]. Lee MM, et al. Pipoxolan inhibits CL1-5 lung cancer cells migration and invasion through inhibition of MMP-9 and MMP-2. Chem Biol Interact. 2015;236:19-30.  [Content Brief]