Home Angiogenesis HIF inhibitor - Apoptosis related activator PX-478 2HCl For research use only.

PX-478 2HCl

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.

PX-478 2HCl Chemical Structure

PX-478 2HCl Chemical Structure

CAS No. 685898-44-6

Purity & Quality Control

PX-478 2HCl Related Products

Signaling Pathway

HIF Signaling Pathways

HIF Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
TW03-EBV cells Function assay 10 μM 24 h suppress HIF-1α expression 30479336
H460 Function assay 10 μM reduced glucose uptake and lactate production rate 30128035
A549 Function assay 10 μM reduced glucose uptake and lactate production rate 30128035
SMMC7721 Function assay 25 μM 24 h inhibits migration of SMMC7721 29495380
EC9706 Function assay 20 μM PX-478 inhibited normoxic and hypoxia-induced HIF-1α expression as well as COX-2 and PD-L1 expression 28560067
EC109 Function assay 20 μM PX-478 inhibited normoxic and hypoxia-induced HIF-1α expression as well as COX-2 and PD-L1 expression 28560067
Tca8113 Function assay 0, 5, and 25 μM 24 h reduces cellular autophagy 26640316
PDAC cell lines Function assay 25 μM 24 h induced a translocation of HMGB1 from the nucleus to the cytoplasm 25544770
PC3 Function assay 20 hr IC50 for HIF-1α inhibition for PC3 cells under normoxic condition was 20-25 μmol/L 18729192
DU 145 Function assay 20 hr IC50 for HIF-1α inhibition for the DU 145 cells was ~40-50 μmol/L 18729192
MCF7 Antiproliferative assay 72 hrs Antiproliferative activity against human MCF7 cells after 72 hrs under hypoxic condition by MTT assay, IC50 = 19.7 μM. 28209257
MCF7 Function assay 24 hrs Inhibition of HIF-1alpha (unknown origin) transcriptional activity expressed in human MCF7 cells after 24 hrs under hypoxic condition by HRE luciferase reporter gene assay , IC50 = 20.2 μM. 28209257
MDA-MB-468 Antiproliferative assay 72 hrs Antiproliferative activity against human MDA-MB-468 cells after 72 hrs under hypoxic condition by MTT assay, IC50 = 45.1 μM. 28209257
Click to View More Cell Line Experimental Data

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
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]
Cell Research Cell lines NPC cell lines
Concentrations 10 μM
Incubation Time 24 h
Method

Cells were treated with 10 or 50 μM PX-478
Experimental Result Images Methods Biomarkers Images PMID
Western blot HIF-1α VEGF / Angiopoietin 1 E-cadherin / N-cadherin / Vimentin HIF-1α VEGF / Angiopoietin 1 E-cadherin / N-cadherin / Vimentin 18729192
Growth inhibition assay Cell viability Cell viability 28052321
In Vivo
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]
Animal Research 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.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00522652 Completed
Advanced Solid Tumors|Lymphoma
Cascadian Therapeutics Inc.|Seagen Inc.
 August 2007 Phase 1

Chemical Information & Solubility

Molecular Weight 394.12 Formula

C13H20Cl4N2O3
CAS No. 685898-44-6 SDF Download PX-478 2HCl SDF
Smiles C1=CC(=CC=C1CC(C(=O)O)N)[N+](CCCl)(CCCl)[O-].Cl.Cl
Storage (From the date of receipt) 3 years -20°C powder (seal)

In vitro
Batch:

DMSO : 79 mg/mL ( (200.44 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : 79 mg/mL

Ethanol : 79 mg/mL


Molecular Weight Calculator

In vivo
Batch:

Add solvents to the product individually and in order.


In vivo Formulation Calculator

Preparing Stock Solutions

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.
Tags: buy PX-478 2HCl | PX-478 2HCl supplier | purchase PX-478 2HCl | PX-478 2HCl cost | PX-478 2HCl manufacturer | order PX-478 2HCl | PX-478 2HCl distributor