PX-12

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Chemical Structure| 141400-58-0 同义名 : IV-2;DB05448;1-methyl propyl 2-imidazolyl disulfide
CAS号 : 141400-58-0
货号 : A112791
分子式 : C7H12N2S2
纯度 : 99%+
分子量 : 188.314
MDL号 : MFCD18086851
存储条件：

Pure form Sealed in dry,2-8°C

In solvent -20°C:6个月-80°C:12个月
溶解度 :

DMSO: 45 mg/mL(238.96 mM)，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

无水乙醇: 50 mg/mL(265.51 mM)，配合低频超声助溶，注意：无水乙醇开封后，易挥发，也会吸收空气中的水分，导致溶解能力下降，请避免使用开封较久的乙醇
动物实验配方：

2% DMSO+30% PEG 300+water 11 mg/mL

生物活性
靶点

  • Thioredoxin
描述 The high expression of redox protein thioredoxin-1 (Trx-1) has been reported in many human cancers, which increases the resistance of cells to apoptosis and induces the production of angiogenic factors. PX-12 is a potent inhibitor of Trx-1. It inhibits the growth of HT-29 and MCF-7 cells with IC50 values of 2.9  2.0μM and 1.9  0.8μM, respectively. The exposure of MCF-7 cells with PX-12 during hypoxia dose-dependently reduced the protein expression of hypoxia-inducible factor-1 (HIF-1) with an IC50 of 7.2  0.9μM. PX-12 also resulted in significant inhibition of hypoxia-induced HIF-1 trans-activating activity in MCF-7 cells with an IC50 of 11.5 ± 1.1μM. The hypoxia-stimulated formation of vascular endothelial growth factor (VEGF) was decreased by PX-12 treatment in both MCF-7 and HT-29 cells with IC50 values of 10.4 ± 2.5 and 10.1 ± 2.2μM, respectively. In mice with MCF-7 tumor xenografts, i.p. administration of 12mg/kg PX-12 significantly decreased VEGF protein expression and microvessel density 24 hours after the injection as compared with untreated animals[3]. PX-12 at 0.1-100μM inhibits the thioredoxin system mediated gp120 reduction in a concentration dependent manner, thus showing anti-HIV-1 activity in TZM-bl cells[4].
作用机制 PX-12 potently inhibits Trx-1 via the irreversible thioalkylation of the Cys73 residue, leading to the inhibition of Trx-dependent cell growth[3].
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT00736372 Metastatic Cancer ... 展开 >> Advanced Cancer 收起 << Phase 1 Completed - United States, Arizona ... 展开 >> TGen Clinical Research Services at Scottsdale Healthcare Scottsdale, Arizona, United States, 85258 United States, South Carolina Cancer Centers of the Carolinas Greenville, South Carolina, United States, 29605 United States, Texas Tyler Cancer Center Tyler, Texas, United States, 75702 收起 <<
NCT00417287 Pancreatic Neoplasms Phase 2 Terminated(Investigator decisi... 展开 >>on) 收起 << - United States, Arizona ... 展开 >> TGen Clinical Research Services at Scottsdale Healthcare Scottsdale, Arizona, United States, 85258 Arizona Cancer Center, University of Arizona Tucson, Arizona, United States, 85724 United States, Texas The University of Texas M.D. Anderson Cancer Center Houston, Texas, United States, 77030 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

5.31mL

1.06mL

0.53mL

26.55mL

5.31mL

2.66mL

53.10mL

10.62mL

5.31mL
参考文献

[1]Kim YH, Coon A, et al. Antitumor agent PX-12 inhibits HIF-1α protein levels through an Nrf2/PMF-1-mediated increase in spermidine/spermine acetyl transferase. Cancer Chemother Pharmacol. 2011 Aug;68(2):405-13.

[2]Welsh SJ, Williams RR, et al. The thioredoxin redox inhibitors 1-methylpropyl 2-imidazolyl disulfide and pleurotin inhibit hypoxia-induced factor 1alpha and vascular endothelial growth factor formation. Mol Cancer Ther. 2003 Mar;2(3):235-43.

[3]Welsh SJ, Williams RR, Birmingham A, Newman DJ, Kirkpatrick DL, Powis G. The thioredoxin redox inhibitors 1-methylpropyl 2-imidazolyl disulfide and pleurotin inhibit hypoxia-induced factor 1alpha and vascular endothelial growth factor formation. Mol Cancer Ther. 2003 Mar;2(3):235-43.

[4] Lundberg M, Mattsson Å, Reiser K, Holmgren A, Curbo S. Inhibition of the thioredoxin system by PX-12 (1-methylpropyl 2-imidazolyl disulfide) impedes HIV-1 infection in TZM-bl cells. Sci Rep. 2019 Apr 4;9(1):5656.