PPM-18  (Synonyms: NSC 73233)

PPM-18 (NSC 73233) is a Vitamin K (HY-B2172) analog. PPM-18 prevents LPS-induced IκBα degradation, thereby inhibiting NF-κB activation and nuclear translocation of NF-κB. PPM-18 inhibits LPS-induced nitrite production and iNOS expression. PPM-18 inhibits HDAC6. PPM-18 induces ROS accumulation, activates AMPK, inhibits the mTORC1 and PI3K/AKT pathways, initiates Autophagy, and induces Apoptosis. PPM-18 suppresses seizures in zebrafish and mouse epilepsy models. PPM-18 prevents LPS-induced lethal toxicity and delayed hypotension. PPM-18 exhibits anticancer activity against leukemia and bladder cancer. PPM-18 can be used in research related to septic shock, bladder cancer and atherosclerosis^[1][2][3].

PPM-18 (0.1-10 µM; 24 h) inhibits lipopolysaccharide (LPS)-induced nitric oxide production (measured by nitrite content) in rat alveolar macrophages in a dose-dependent manner, with the maximal inhibitory effect observed at 10 µM^[1].
PPM-18 (3-10 µM; 24 h) inhibits lipopolysaccharide (LPS)-induced iNOS protein expression in rat alveolar macrophages^[1].
PPM-18 (3-10 µM; preincubated prior to 6 h LPS stimulation) inhibits lipopolysaccharide (LPS)-induced accumulation of iNOS mRNA in rat alveolar macrophages^[1].
PPM-18 (10 µM; 60 min preincubation prior to 30 min LPS stimulation) inhibits lipopolysaccharide (LPS)-induced nuclear translocation of NF-κB p65 in rat alveolar macrophages^[1].
PPM-18 (10-30 µM; 60 min preincubation prior to 30 min LPS stimulation for whole-cell assays) inhibits lipopolysaccharide (LPS)-induced NF-κB-DNA binding activity in intact rat alveolar macrophages, but does not directly interfere with NF-κB-DNA binding in isolated nuclear extracts^[1].
PPM-18 (10 µM; 24 h) inhibits LPS-induced TNF-α release from rat alveolar macrophages^[1].
PPM-18 (5-20 μM; 6-24 h) reduces the viability of bladder cancer T24 and EJ cells in a dose- and time-dependent manner^[2].
PPM-18 (5-15 μM; 24 h) induces autophagy in bladder cancer T24 and EJ cells in a dose-dependent manner, and this effect can be detected by decreased p62 expression and increased LC3B II expression^[2].
PPM-18 (10 μM; 1 h) completely inhibits shear-induced nuclear translocation of NF-κB subunits p50 and p65^[3].

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

PPM-18 (5-15 mg/kg; i.p.; single dose; 2 hours prior to LPS) confers dose-dependent protection against LPS-induced lethal sepsis in Balb/c mice, with 70% protection at 15 mg/kg^[1].
PPM-18 (15 mg/kg; i.v.; single dose; 20 minutes prior to LPS) prevents delayed hypotension and inhibits LPS-induced increases in total plasma nitrite in a rat model of endotoxic shock^[1].
PPM-18 (10 mg/kg; intratumoral injection; daily; 30 days) inhibits bladder cancer xenograft growth, increases tumor cell autophagy and apoptosis via ROS and AMPK pathways, improves mouse survival to 85.7%, and exhibits low in vivo toxicity^[2].

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

277.27

C₁₇H₁₁NO₃

65240-86-0

Solid

Orange to red

O=C(NC(C1=O)=CC(C2=C1C=CC=C2)=O)C3=CC=CC=C3

Room temperature in continental US; may vary elsewhere.

• [1]. Yu SM, et al. Inhibition of nitric oxide synthase expression by PPM-18, a novel anti-inflammatory agent, in vitro and in vivo. Biochem J. 1997;328 ( Pt 2)(Pt 2):363-369.  [Content Brief]

  [2]. Lu H, et al. PPM-18, an Analog of Vitamin K, Induces Autophagy and Apoptosis in Bladder Cancer Cells Through ROS and AMPK Signaling Pathways. Front Pharmacol. 2021;12:684915. Published 2021 Jul 9.  [Content Brief]

  [3]. Davis ME, et al. Shear stress regulates endothelial nitric-oxide synthase promoter activity through nuclear factor kappaB binding. J Biol Chem. 2004;279(1):163-168.