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PX-478·2HCl

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Chemical Structure| 685898-44-6 同义名 : PX-478 2HCl
CAS号 : 685898-44-6
货号 : A812611
分子式 : C13H22Cl4N2O3
纯度 : 98%+
分子量 : 396.137
MDL号 : MFCD11840749
存储条件：

粉末 Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(265.06 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

H2O: 35 mg/mL(88.35 mM)
动物实验配方：
生物活性
靶点

  • HIF
描述 HIF-1α is constitutively expressed subunit of HIF-1 mediating the cellular response to hypoxia, which can be rapidly degraded by the ubiquitin-26S proteasome pathway under conditions of normoxia. PX-478 target on HIF-1α, which can selectively inhibit the hypoxia-induced increase in HIF-1a protein. Treatment with PX-478 for 16h can inhibit nuclear HIF-1αprotein level in cell lines under hypoxic (1% O2, 5%CO2, 94% N2) compared with cells under normoxia (air, 5% CO2) with IC50 values for PC-3 prostate cancer cells of 3.9 ± 2.0 μM, MCF-7 breast cancer cells of 4.0 ± 2.0 μM, HT-29 colon cancer cells of 19.4 ± 5.0 μM, Panc-1 pancreatic cancer cells of 10.1 ± 1.9 μM and BxPC-3 pancreatic cancer cells of 15.3 ± 4.8 μM, without affection on levels of HIF-1βprotein. Meanwhile, PX-478 treatment also significantly decreased the activity of a HIF-1 (measured by transiently transfected HIF-1 reporter), as well as hypoxia-induced expression of VEGF, a HIF-1-regulated protein, in MCF-7 cells in a dose-dependent manner (0 - 25 μM, for 16h) but did not affect basal levels of VEGF formation under normoxic conditions[1]. Treatment with PX-478, i.p., at dose of 75 or 100 mg/kg/day repressed tumor growth in female SCID mice were implanted, s.c., with SHP-77 human small cell lung cancer cells. Also treatment with PX-478, i.p., at dose of 100mg/kg/day suppressed tumor growth in male SCID mice implanted s.c. with PC-3 prostate cancer cells[2]. Up to now, phase 1 studies of PX-478 treatment for advanced solid tumors and lymphoma have been completed (see https://www.clinicaltrials.gov/)
作用机制 The action of PX-478 on HIF-1αmay due to: 1. Modulation of HIF-1αubiquitination; 2. Inhibition on HIF-1α transcription; 3. Inhibition on HIF-1α translation.
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.52mL

0.50mL

0.25mL

12.62mL

2.52mL

1.26mL

25.24mL

5.05mL

2.52mL
参考文献

[1]Koh MY, Spivak-Kroizman T, et al. Molecular mechanisms for the activity of PX-478, an antitumor inhibitor of the hypoxia-inducible factor-1alpha. Mol Cancer Ther. 2008 Jan;7(1):90-100.

[2]Welsh S, Williams R, et al. Antitumor activity and pharmacodynamic properties of PX-478, an inhibitor of hypoxia-inducible factor-1alpha. Mol Cancer Ther. 2004 Mar;3(3):233-44.

[3]Small-molecule inhibitors of HIF-PHD2: a valid strategy to renal anemia treatment in clinical therapy