product name PX-478 2HCl
Description: PX-478 is an orally active small molecule HIF-1alpha inhibitor with potential antineoplastic activity. Although its mechanism of action has yet to be fully elucidated, PX-478 appears to inhibit hypoxia-inducible factor 1-alpha (HIF1A) expression, which may result in decreased expression of HIF1A downstream target genes important to tumor growth and survival, a reduction in tumor cell proliferation, and the induction of tumor cell apoptosis. The inhibitory effect of this agent is independent of the tumor suppressor genes VHL and p53 and may be related to derangements in glucose uptake and metabolism due to inhibition of glucose transporter-1 (Glut-1).
References: Mol Cancer Ther. 2004 Mar;3(3):233-44; Mol Cancer Ther. 2008 Jan;7(1):90-100.
394.12
Formula
C13H20Cl4N2O3
CAS No.
685898-44-6
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 78 mg/mL (197.9 mM)
Water: 78 mg/mL (197.9 mM)
Ethanol:
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19426607
| In Vitro |
In vitro activity: PX-478 lowers HIF-1α protein levels and HIF-1 transactivation in hypoxia and in normoxia in a variety of cancer cell lines, but has a more pronounced effect on translation of proteins, such as HIF-1α in hypoxia. PX-478 also enhances the radiosensitivity of prostate carcinoma PC3 cells. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | In HT-29 human colon cancer xenografts, PX-478 suppresses HIF-1alpha levels and inhibits the expression of HIF-1 target genes including vascular endothelial growth factor and the glucose transporter-1. In addition, PX-478 (100 or 120 mg/kg i.p.) also shows antitumor activity including cures against several established human tumor xenografts that is related to the levels of HIF-1α. In high-fat-diet mice, PX-478 causes reduced fibrosis and fewer inflammatory infiltrates in their adipose tissues |
| Animal model | Mice bearing MCF-7 human breast cancer, HT-29 colon cancer, PC-3 prostate cancer, DU-145 prostate cancer, OvCar-3 ovarian cancer, A-549 non-small cell lung cancer, SHP-77 small cell lung cancer, and Caki-1 renal cancer, Panc-1, MiaPaCa, or BxPC-3 pancreatic cancer xenografts. |
| Formulation & Dosage | Dissolved in 0.9% NaCl; 100 or 120 mg/kg; i.p. injection |
| References | Mol Cancer Ther. 2004 Mar;3(3):233-44; Mol Cancer Ther. 2008 Jan;7(1):90-100; Int J Cancer. 2008 Nov 15;123(10):2430-7. |
