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PX-478 Dihydrochloride HIF-1α Inhibitor

Name: PX-478 Dihydrochloride
Brand: Selleck Chemicals
SKU: S7612
Availability: InStock
Rating: 5 (85 reviews)

Cat.No.S7612

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.

Chemical Structure

Molecular Weight: 394.12

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: >97%

Related Targets	EGFR VEGFR JAK PDGFR FGFR Src FLT3 HER2 Bcr-Abl BTK ALK Syk FAK VDA
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Cell Culture, Treatment & Working Concentration

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

Chemical Information, Storage & Stability

Molecular Weight	394.12	Formula	C₁₃H₂₀Cl₄N₂O₃	Storage (From the date of receipt)	3 years -20°C powder (seal)
CAS No.	685898-44-6	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	C1=CC(=CC=C1CC(C(=O)O)N)[N+](CCCl)(CCCl)[O-].Cl.Cl

Solubility

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

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
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	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.
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.
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.

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.

Mechanism of Action

Targets/IC₅₀/Ki	HIF-1α ^[1]
In vitro	PX-478 2HCl 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] This compound also enhances the radiosensitivity of prostate carcinoma PC3 cells. ^[3]
In vivo	In HT-29 human colon cancer xenografts, PX-478 2HCl 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, this compound (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, this chemical causes reduced fibrosis and fewer inflammatory infiltrates in their adipose tissues. ^[4]
References	https://pubmed.ncbi.nlm.nih.gov/15026543/ https://pubmed.ncbi.nlm.nih.gov/18202012/ https://pubmed.ncbi.nlm.nih.gov/18729192/ https://pubmed.ncbi.nlm.nih.gov/23249949/ https://pubmed.ncbi.nlm.nih.gov/30479336/

Applications

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

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT00522652	Completed	Advanced Solid Tumors\|Lymphoma	Cascadian Therapeutics Inc.\|Seagen Inc.	August 2007	Phase 1

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