Choose Your Country or Region

PX-478 2HCl

Name: PX-478 2HCl
Brand: Selleck Chemicals
SKU: S7612
Rating: 5 (83 reviews)

Catalog No.S7612 Purity:97%

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

CAS No. 685898-44-6

Purity & Quality Control

Batch: Purity: >97%

PX-478 2HCl Related Products

Related Targets	HIF1 HIF2 PHD1 PHD2 PHD3	Click to Expand
Related Products	BAY 87-2243 KC7F2 Lificiguat (YC-1) IOX2 CAY10585 (LW 6) Molidustat (BAY 85-3934) PT2385 IDF-11774 MK-8617 Daprodustat (GSK1278863) FG-2216 Vadadustat Glucosamine Enarodustat (JTZ-951) SYP-5 IOX4	Click to Expand
Related Compound Libraries	Tyrosine Kinase Inhibitor Library PI3K/Akt Inhibitor Library Angiogenesis Related compound Library HIF-1 Signaling Pathway Compound Library FDA-approved Anticancer Drug Library	Click to Expand

Signaling Pathway

HIF Signaling Pathway

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	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
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT00522652	Completed	Advanced Solid Tumors\|Lymphoma	Cascadian Therapeutics Inc.\|Seagen Inc.	August 2007	Phase 1

References

+ Expand

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)	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years -20°C powder (seal)		1 month-20°Cin solvent

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
Clear solution	saline	79.000mg/ml (200.45mM)	Taking the 1 mL working solution as an example, add 79 mg of this product to 1 ml of physiological saline (0.9% NaCL solution), mix evenly to make it clear, The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	3.950mg/ml (10.02mM)	Taking the 1 mL working solution as an example, add 50 μL of clarified DMSO stock solution of 79 mg/ml to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	saline Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	10.000mg/ml (25.37mM)	Taking the 1 mL working solution as an example, add 10 mg of product to 1 ml of physiological saline (0.9% NaCL solution), and shake to clarify. The mixed solution should be used immediately for optimal results.
Clear solution	saline	79.000mg/ml (200.45mM)	Taking the 1 mL working solution as an example, add 79 mg of this product to 1 ml of physiological saline (0.9% NaCL solution), mix evenly to make it clear, The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	saline	79.000mg/ml (200.45mM)	Taking the 1 mL working solution as an example, add 79 mg of this product to 1 ml of physiological saline (0.9% NaCL solution), mix evenly to make it clear, The mixed solution should be used immediately for optimal results.
Clear solution	saline	79.000mg/ml (200.45mM)	Taking the 1 mL working solution as an example, add 79 mg of this product to 1 ml of physiological saline (0.9% NaCL solution), mix evenly to make it clear, The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	saline	79.000mg/ml (200.45mM)	Taking the 1 mL working solution as an example, add 79 mg of this product to 1 ml of physiological saline (0.9% NaCL solution), mix evenly to make it clear, The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Preparing Stock Solutions

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Formulation Calculator (Clear solution)

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

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

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

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):