Product Information
| Molecular Weight: |
394.12 |
| Formula: |
C13H20Cl4N2O3 |
| Purity: |
≥98% |
| CAS#: |
685898-44-6 |
| Solubility: |
DMSO up to 100 mM |
| Chemical Name: |
4-[bis(2-chloroethyl)oxidoamino]-L-phenylalanine hydrochloride |
| Storage: |
Powder: 4oC 1 year.
DMSO: 4oC 3 month;
-20oC 1 year. |
Biological Activity:
PX-478 is a highly potent and selective Hypoxia-inducible
Factor-1α (HIF-1α) inhibitor. ?It 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.
Its inhibition 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). PX-478 has
excellent activity against established human tumor xenografts, inducing tumor
regressions with prolonged growth delays which correlate positively with HIF-1
levels. In high-fat-diet
mice, PX-478 causes reduced fibrosis and fewer inflammatory infiltrates in
their adipose tissues. Currently it is in phase I clinical trials for cancer
patients.
How to Use:
In vitro:? PX-478 was used at 1-10 μM final concentration
in various in vitro assays. It is found to be not stable at basic buffer, and
stable in acidic buffer.
In vivo: PX-478 was dosed to mice
bearing tumor via IP injection or oral gavage at 100-120 mg/kg once per day. Formulation
is 0.9% NaCl. Xenografts models are 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.?
Reference:
- 1.?????
Welsh
S, et al. Antitumor activity and pharmacodynamic properties of PX-478, an
inhibitor of hypoxia-inducible factor-1alpha. (2004) Mol Cancer Ther. 3(3):233-44.
- 2.?????
Koh
MY, et al. Molecular mechanisms for the activity of PX-478, an antitumor
inhibitor of the hypoxia-inducible factor-1alpha. (2008) Mol Cancer Ther.
7(1):90-100.
- 3.?????
Palayoor
ST, et al. PX-478, an inhibitor of hypoxia-inducible factor-1alpha, enhances
radiosensitivity of prostate carcinoma cells. (2008) Int J Cancer.
123(10):2430-7.
- 4.?????
Sun
K, et al. Selective inhibition of hypoxia-inducible factor 1α ameliorates
adipose tissue dysfunction. (2013) Mol Cell Biol. 33(5):904-17.
?
Products are for research
use only. Not for human use.?
