Name: PX-478 2HCl
Price: 260.00 USD

- Overview
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    Background
    
    PX-478 2HCl, also called PX-478, is an experimental HIF-1α inhibitor. It inhibited HIF-1α protein at multiple levels in cancer cell lines under normoxia and hypoxia with an IC50 value of ~20-30 μM [1].Hypoxia-inducible transcription factor HIF-1α activates target genes involved in glycolysis, erythropoiesis and angiogenesis. HIF-1α also regulates the expression of genes coding for apoptotic pathway, growth factors/receptors, cell cycle regulators, metastasis and invasiveness [1].Under normoxic condition, the IC50 for PX-478 to inhibit HIF-1α in PC3 cells was 20-25 μmol/L, whereas the IC50 for PX-478 to inhibit HIF-1α in the DU 145 cells was ~40-50 μmol/L. in both DU 145 and PC3 cells, 1-hr hypoxia significantly upregulated HIF-1α protein. But the pretreatment with PX-478 for 20 hr under normoxia before 1-hr hypoxia attenuated the accumulation of HIF-1α induced by the 1-hr hypoxia. In PC3 cells, pretreatment with 20 μmol/L PX-478 before hypoxia inhibited HIF-1α by 40% compared to treatment with hypoxia alone. In DU 145 cells, pretreatment with 50 μmol/L PX-478 before hypoxia inhibited HIF-1α by 35% compared to treatment with hypoxia alone [1].In nu/nu mice with C6 reporter xenografts, treatment with PX-478 at a dose of 30 mg/kg p.o. for 2 consecutive days prevented the transcriptional activity of HIF-1 in central ischemic regions of C6 tumors [2].
    
    [1]. Palayoor ST, Mitchell JB, Cerna D, et al. PX-478, an inhibitor of hypoxia-inducible factor-1α, enhances radiosensitivity of prostate carcinoma cells. International journal of cancer, 2008, 123(10): 2430-2437.
    [2]. Schwartz DL, Powis G, Thitai-Kumar A, et al. The selective hypoxia inducible factor-1 inhibitor PX-478 provides in vivo radiosensitization through tumor stromal effects. Molecular cancer therapeutics, 2009, 8(4): 947-958.
- Properties
  - Alternative Name
    
    (S)-4-(2-amino-2-carboxyethyl)-N,N-bis(2-chloroethyl)aniline oxide dihydrochloride
    
    CAS Number
    
    685898-44-6
    
    Molecular Formula
    
    C13H20Cl4N2O3
    
    Molecular Weight
    
    394.12
    
    Purity
    
    98.00%
    
    Solubility
    
    ≥19.7 mg/mL in DMSO; ≥50 mg/mL in H2O; ≥8.42 mg/mL in EtOH
    
    Storage
    
    Store at -20°C
    
    * For Research Use Only
- Reference
  - 1. Qiu-yan Liu, Yu Zhuang, et al. "Tanshinone IIA prevents LPS-induced inflammatory responses in mice via inactivation of succinate dehydrogenase in macrophages." Acta Pharmacol Sin. 2020 Oct 7. PMID:33028985
    2. Peng H, Purkerson JM, et al. "Acidosis induces antimicrobial peptide expression and resistance to uropathogenic E coli infection in kidney collecting duct cells via HIF-1α." Am J Physiol Renal Physiol. 2019 Dec 16. PMID:31841391