PX-478

SKU: orb1300310

Description

PX-478 is a selective, orally active, and blood-brain barrier permeable HIF-1α inhibitor. It demonstrates antitumor activity in cancer research and has been shown in studies to protect pancreatic β-cell function, making it a compound of interest for type 2 diabetes research.

Research Area

Cardiovascular Research, Cell Biology, Epigenetics & Chromatin, Metabolism Research

Key Properties

• CAS Number: 685898-44-6
• MW: 394.12
• Purity: 97.93%
• Formula: C₁₃H₂₀Cl₄N₂O₃
• SMILES: Cl.Cl.N[C@@H](Cc1ccc(cc1)[N+]([O-])(CCCl)CCCl)C(O)=O
• Target: HIF,Autophagy,HIF/HIF Prolyl-Hydroxylase
• Solubility: DMSO:50 mg/mL (126.86 mM);H2O:88.81 mM;10% DMSO+40% PEG300+5% Tween 80+45% Saline:5 mg/mL (12.69 mM)

Bioactivity

• Target IC50:
  MCF-7 cells (normoxia):20.0 µM|HT29 cells (normoxia):23.9 µM|PC3 cells inhibit HIF-1α:20-25 µM|PC3 cells (anoxia):16.2 µM|PC3 cells (normoxia):11.1 µM|HT29 cells (anoxia):29.5 µM|DU-145 cells inhibit HIF1α:40-50 µM|MCF-7 cells (anoxia):25.1 µM
• In Vivo:
  METHODS: To study the activity on metabolism in vivo, PX-478 (5 mg/kg) was administered by gavage to C57BL/6 mice on a high-fat diet (HFD) every two days for seven weeks. RESULTS: PX-478 treatment effectively inhibited HFD-induced HIF1α activation in adipose tissue. Inhibition of HIF1α in adipocytes significantly improved metabolism. METHODS: In order to detect the anti-tumor activity in vivo, PX-478 (75-100 mg/kg) was intraperitoneally injected into scid mice carrying tumors OvCar-3, SHP-77, MCF-7, or PC-3 once a day for five days. RESULTS: PX-478 showed antitumor activity against established human tumor xenografts.
• In Vitro:
  METHODS: Tumor cells MCF-7, HT-29 and PC-3 were treated with PX-478 under normoxic or hypoxic conditions for 16 h, and then grown under normoxic conditions for another 56 h. Cell viability was detected by MTT assay. RESULTS: PX-478 produced a smaller but significantly greater inhibition of cell growth under hypoxic conditions compared to normoxic conditions. the hypoxic/normoxic IC50 of MCF-7 cells was 25.1/20.0 µM, with a ratio of 1.25. the hypoxic/normoxic IC50 of HT-29 cells was 29.5/23.9 µM, with a ratio of 1.20, and that of PC-3 cells was 16.2/11.9 µM, with a ratio of 16.2/11.0 µM. IC50 for PC-3 cells was 16.2/11.1 µM with a ratio of 1.45. METHODS: Human prostate cancer cells PC3 and DU 145 were treated with PX-478 (10-40 µM) under normoxic conditions for 20 h. The expression levels of target proteins were detected by Western Blot. RESULTS: Under normoxic conditions, the IC50 of PX-478 for HIF-1α inhibition in PC3 cells was 20-25 µM (ΔHIF:0.56±0.08), while the IC50 of HIF1α inhibition in DU 145 cells was 40-50 µM (ΔHIF:0.47±0.08).
• Cell Research:
  PX-478 is prepared as a 10 mM stock in distilled water and used immediately. To determine the effect of PX-478 in combination with radiation, cells are treated with PX-478 for 24 hr under normoxic condition, irradiated and plated after 1 hr. Colonies are stained with crystal violet after 12 days and the colonies of >50 cells are counted. For combination treatments, net survival is calculated by correcting the toxicity of PX-478 alone. Enhancement factor (EF) is calculated by dividing the dose of radiation required to reduce plating efficiency to 10% when cells are treated with radiation alone by the dose of radiation required to reduce plating efficiency to 10% when cells are treated with PX-478 and radiation.

Storage & Handling

• Storage: store under nitrogen,keep away from moisture,store at low temperature | -20°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Autophagy, HIFProlylHydroxylase, HIF ProlylHydroxylase, HIF Prolyl-Hydroxylase, HIF/HIF Prolyl-Hydroxylase, HIF/HIFProlylHydroxylase, HIF/HIF ProlylHydroxylase, HIF-1α, HIF, PX478, PX-478, PX 478

Compound Identifiers

PubChem CID

11234794