| Name | PX-478 |
| Description | PX-478 is a HIF-1α inhibitor with selectivity, oral activity, and blood-brain barrier permeability. PX-478 has antitumor activity and also protects pancreatic β-cell function in diabetes mellitus and is used in type 2 diabetes mellitus research. |
| Cell Research | PX-478 is prepared as a 10 mM stock in distilled water and used immediately[1]. 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[1]. |
| 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. [1]
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). [2] |
| 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. [3]
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. [4] |
| Storage | store under nitrogen,keep away from moisture,store at low temperature | Shipping with blue ice/Shipping at ambient temperature. |
| Solubility Information | 10% DMSO+40% PEG300+5% Tween 80+45% Saline : 5 mg/mL (12.69 mM), Sonication is recommended.
DMSO : 50 mg/mL (126.86 mM), Sonication is recommended.
H2O : 88.81 mM, Sonication is recommended.
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| Keywords | PX-478 | PX478 | PX 478 | HIFProlylHydroxylase | HIF-1α | HIF/HIFProlylHydroxylase | HIF/HIF Prolyl-Hydroxylase | HIF/HIF ProlylHydroxylase | HIF Prolyl-Hydroxylase | HIF ProlylHydroxylase | HIF | Autophagy |
| Inhibitors Related | Stavudine | Aceglutamide | Hemin | Tamoxifen | Cysteamine hydrochloride | Guanidine hydrochloride | Hydroxychloroquine | Enzalutamide | Paeonol | Naringin | Alginic acid | Sildenafil citrate |
| Related Compound Libraries | Bioactive Compound Library | Anti-Cancer Clinical Compound Library | Drug Repurposing Compound Library | Angiogenesis related Compound Library | CNS-Penetrant Compound Library | Inhibitor Library | Immunology/Inflammation Compound Library | Anti-Aging Compound Library | Clinical Compound Library | Bioactive Compounds Library Max | Anti-Cancer Drug Library | Anti-Cancer Active Compound Library |
United States
