PX-478 2HCl

Catalog No.S7612 Batch:S761203

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Technical Data

Formula

C13H20Cl4N2O3
Molecular Weight 394.12 CAS No. 685898-44-6
Solubility (25°C)* In vitro DMSO 79 mg/mL (200.44 mM)
Water 79 mg/mL (200.44 mM)
Ethanol 20 mg/mL (50.74 mM)
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description PX-478 2HCl is an orally active, and selective hypoxia-inducible factor-1α (HIF-1α) inhibitor. PX-478 2HCl induces apoptosis and has anti-tumor activity. Phase 1.
Targets
HIF-1α [1]
In vitro

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. [2]

PX-478 also enhances the radiosensitivity of prostate carcinoma PC3 cells. [3]
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. [1]

In high-fat-diet mice, PX-478 causes reduced fibrosis and fewer inflammatory infiltrates in their adipose tissues. [4]

Protocol (from reference)

Cell Assay:

[5]
  • Cell lines

    NPC cell lines

  • Concentrations

    10 μM

  • Incubation Time

    24 h

  • Method

    Cells were treated with 10 or 50 μM PX-478
Animal Study:

[1]
  • Animal Models

    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.

  • Dosages

    100 or 120 mg/kg

  • Administration

    i.p.

Customer Product Validation

Data from [Data independently produced by , , Theranostics, 2018, 8(15):4050-4061]

Data from [Data independently produced by , , Free Radic Biol Med, 2018, 130:278-287]

Data from [Data independently produced by , , Br J Pharmacol, 2017, 174(5):409-423]

Data from [Data independently produced by , , Am J Cancer Res, 2017, 7(5):1198-1212]

Selleck's PX-478 2HCl has been cited by 83 publications

Oxygen enhances antiviral innate immunity through maintenance of EGLN1-catalyzed proline hydroxylation of IRF3 [ Nat Commun, 2024, 15(1):3533] PubMed: 38670937
Wild-type IDH2 is a therapeutic target for triple-negative breast cancer [ Nat Commun, 2024, 15(1):3445] PubMed: 38658533
Single-embryo transcriptomic atlas of oxygen response reveals the critical role of HIF-1α in prompting embryonic zygotic genome activation [ Redox Biol, 2024, 72:103147] PubMed: 38593632
HIF1A contributes to the survival of aneuploid and mosaic pre-implantation embryos [ bioRxiv, 2024, 2023.09.04.556218] PubMed: 39071426
Targeting PLOD2 suppresses invasion and metastatic potential in radiorecurrent prostate cancer [ BJC Rep, 2024, 2(1):60] PubMed: 39184453
PD-1 instructs a tumor-suppressive metabolic program that restricts glycolysis and restrains AP-1 activity in T cell lymphoma [ Nat Cancer, 2023, 4(10):1508-1525] PubMed: 37723306
AMPK-HIF-1α signaling enhances glucose-derived de novo serine biosynthesis to promote glioblastoma growth [ J Exp Clin Cancer Res, 2023, 42(1):340] PubMed: 38098117
Hypoxia-inducible factor 1A inhibition overcomes castration resistance of prostate tumors [ EMBO Mol Med, 2023, e17209.] PubMed: 37070472
Hypoxia-inducible factor 1α modulates interstitial pneumonia-mediated lung cancer progression [ J Transl Med, 2023, 21(1):857] PubMed: 38012636
Hypoxia Primes Human ISCs for Interleukin-Dependent Rescue of Stem Cell Activity [ Cell Mol Gastroenterol Hepatol, 2023, 10.1016/j.jcmgh.2023.07.012] PubMed: 37562653

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.