Page last updated: 2024-11-12

px 478

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Description

2-amino-3-(4'-N,N-bis(2-chloroethyl)amino)phenylpropionic acid N-oxide: inhibits hypoxia-inducible factor-1alpha [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID11234794
CHEMBL ID4061538
SCHEMBL ID18548830
MeSH IDM0475249

Synonyms (29)

Synonym
px-478 ,
px478
unii-t23u22x160
l-phenylalanine, 4-(bis(2-chloroethyl)oxidoamino)-, dihydrochloride
t23u22x160 ,
px 478
685898-44-6
2-amino-3-(4'-n,n-bis(2-chloroethyl)amino)phenylpropionic acid n-oxide
S7612
px 478 [who-dd]
HY-10231
CS-5164
DTXSID00218688
(s)-4-(2-amino-2-carboxyethyl)-n,n-bis(2-chloroethyl)aniline oxide dihydrochloride
AC-35272
AKOS030231369
SCHEMBL18548830
px-478 2hcl
px-478 hcl
685898-44-6 (hcl)
DB06082
4-(bis(2-chloroethyl)oxidoamino)-l-phenylalanine 2hcl
bdbm50231387
EX-A4655
CHEMBL4061538 ,
CCG-268582
Q27289565
AS-76128
A867013

Research Excerpts

Bioavailability

ExcerptReferenceRelevance
" We initially confirmed that the orally bioavailable HIF-1 inhibitor PX-478 reduces HIF-1 protein levels and signaling in vitro in a dose-dependent manner and provides direct radiosensitization of hypoxic cancer cells in clonogenic survival assays using C6 glioma, HN5 and UMSCCa10 squamous cells, and Panc-1 pancreatic adenocarcinoma cell lines."( The selective hypoxia inducible factor-1 inhibitor PX-478 provides in vivo radiosensitization through tumor stromal effects.
Alauddin, M; Bankson, J; Bornmann, W; Gelovani, J; He, Y; Lemos, R; Mukhopadhay, U; Nishii, R; Oh, J; Peng, Z; Powis, G; Schwartz, DL; Soghomonyan, S; Thitai-Kumar, A; Volgin, A; Williams, R, 2009
)
0.35
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (1)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Hypoxia-inducible factor 1-alphaHomo sapiens (human)IC50 (µMol)20.20000.00072.46529.2100AID1427242
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (84)

Processvia Protein(s)Taxonomy
positive regulation of chemokine-mediated signaling pathwayHypoxia-inducible factor 1-alphaHomo sapiens (human)
positive regulation of signaling receptor activityHypoxia-inducible factor 1-alphaHomo sapiens (human)
response to hypoxiaHypoxia-inducible factor 1-alphaHomo sapiens (human)
regulation of DNA-templated transcriptionHypoxia-inducible factor 1-alphaHomo sapiens (human)
positive regulation of transcription by RNA polymerase IIHypoxia-inducible factor 1-alphaHomo sapiens (human)
response to reactive oxygen speciesHypoxia-inducible factor 1-alphaHomo sapiens (human)
angiogenesisHypoxia-inducible factor 1-alphaHomo sapiens (human)
response to hypoxiaHypoxia-inducible factor 1-alphaHomo sapiens (human)
intracellular glucose homeostasisHypoxia-inducible factor 1-alphaHomo sapiens (human)
neural crest cell migrationHypoxia-inducible factor 1-alphaHomo sapiens (human)
epithelial to mesenchymal transitionHypoxia-inducible factor 1-alphaHomo sapiens (human)
embryonic placenta developmentHypoxia-inducible factor 1-alphaHomo sapiens (human)
B-1 B cell homeostasisHypoxia-inducible factor 1-alphaHomo sapiens (human)
positive regulation of endothelial cell proliferationHypoxia-inducible factor 1-alphaHomo sapiens (human)
heart loopingHypoxia-inducible factor 1-alphaHomo sapiens (human)
positive regulation of neuroblast proliferationHypoxia-inducible factor 1-alphaHomo sapiens (human)
chondrocyte differentiationHypoxia-inducible factor 1-alphaHomo sapiens (human)
glandular epithelial cell maturationHypoxia-inducible factor 1-alphaHomo sapiens (human)
connective tissue replacement involved in inflammatory response wound healingHypoxia-inducible factor 1-alphaHomo sapiens (human)
outflow tract morphogenesisHypoxia-inducible factor 1-alphaHomo sapiens (human)
cardiac ventricle morphogenesisHypoxia-inducible factor 1-alphaHomo sapiens (human)
lactate metabolic processHypoxia-inducible factor 1-alphaHomo sapiens (human)
regulation of glycolytic processHypoxia-inducible factor 1-alphaHomo sapiens (human)
regulation of DNA-templated transcriptionHypoxia-inducible factor 1-alphaHomo sapiens (human)
intracellular iron ion homeostasisHypoxia-inducible factor 1-alphaHomo sapiens (human)
signal transductionHypoxia-inducible factor 1-alphaHomo sapiens (human)
neuroblast proliferationHypoxia-inducible factor 1-alphaHomo sapiens (human)
lactationHypoxia-inducible factor 1-alphaHomo sapiens (human)
visual learningHypoxia-inducible factor 1-alphaHomo sapiens (human)
response to iron ionHypoxia-inducible factor 1-alphaHomo sapiens (human)
regulation of gene expressionHypoxia-inducible factor 1-alphaHomo sapiens (human)
vascular endothelial growth factor productionHypoxia-inducible factor 1-alphaHomo sapiens (human)
positive regulation of vascular endothelial growth factor productionHypoxia-inducible factor 1-alphaHomo sapiens (human)
positive regulation of gene expressionHypoxia-inducible factor 1-alphaHomo sapiens (human)
negative regulation of gene expressionHypoxia-inducible factor 1-alphaHomo sapiens (human)
positive regulation of epithelial cell migrationHypoxia-inducible factor 1-alphaHomo sapiens (human)
response to muscle activityHypoxia-inducible factor 1-alphaHomo sapiens (human)
axonal transport of mitochondrionHypoxia-inducible factor 1-alphaHomo sapiens (human)
neural fold elevation formationHypoxia-inducible factor 1-alphaHomo sapiens (human)
cerebral cortex developmentHypoxia-inducible factor 1-alphaHomo sapiens (human)
bone mineralizationHypoxia-inducible factor 1-alphaHomo sapiens (human)
negative regulation of bone mineralizationHypoxia-inducible factor 1-alphaHomo sapiens (human)
positive regulation of vascular endothelial growth factor receptor signaling pathwayHypoxia-inducible factor 1-alphaHomo sapiens (human)
TOR signalingHypoxia-inducible factor 1-alphaHomo sapiens (human)
negative regulation of TOR signalingHypoxia-inducible factor 1-alphaHomo sapiens (human)
intracellular oxygen homeostasisHypoxia-inducible factor 1-alphaHomo sapiens (human)
positive regulation of chemokine productionHypoxia-inducible factor 1-alphaHomo sapiens (human)
regulation of transforming growth factor beta2 productionHypoxia-inducible factor 1-alphaHomo sapiens (human)
collagen metabolic processHypoxia-inducible factor 1-alphaHomo sapiens (human)
cellular response to oxidative stressHypoxia-inducible factor 1-alphaHomo sapiens (human)
embryonic hemopoiesisHypoxia-inducible factor 1-alphaHomo sapiens (human)
insulin secretion involved in cellular response to glucose stimulusHypoxia-inducible factor 1-alphaHomo sapiens (human)
positive regulation of insulin secretion involved in cellular response to glucose stimulusHypoxia-inducible factor 1-alphaHomo sapiens (human)
hemoglobin biosynthetic processHypoxia-inducible factor 1-alphaHomo sapiens (human)
positive regulation of blood vessel endothelial cell migrationHypoxia-inducible factor 1-alphaHomo sapiens (human)
positive regulation of erythrocyte differentiationHypoxia-inducible factor 1-alphaHomo sapiens (human)
positive regulation of angiogenesisHypoxia-inducible factor 1-alphaHomo sapiens (human)
positive regulation of DNA-templated transcriptionHypoxia-inducible factor 1-alphaHomo sapiens (human)
negative regulation of growthHypoxia-inducible factor 1-alphaHomo sapiens (human)
positive regulation of transcription by RNA polymerase IIHypoxia-inducible factor 1-alphaHomo sapiens (human)
muscle cell cellular homeostasisHypoxia-inducible factor 1-alphaHomo sapiens (human)
positive regulation of hormone biosynthetic processHypoxia-inducible factor 1-alphaHomo sapiens (human)
digestive tract morphogenesisHypoxia-inducible factor 1-alphaHomo sapiens (human)
positive regulation of nitric-oxide synthase activityHypoxia-inducible factor 1-alphaHomo sapiens (human)
neuron apoptotic processHypoxia-inducible factor 1-alphaHomo sapiens (human)
elastin metabolic processHypoxia-inducible factor 1-alphaHomo sapiens (human)
intestinal epithelial cell maturationHypoxia-inducible factor 1-alphaHomo sapiens (human)
epithelial cell differentiation involved in mammary gland alveolus developmentHypoxia-inducible factor 1-alphaHomo sapiens (human)
iris morphogenesisHypoxia-inducible factor 1-alphaHomo sapiens (human)
retina vasculature development in camera-type eyeHypoxia-inducible factor 1-alphaHomo sapiens (human)
negative regulation of thymocyte apoptotic processHypoxia-inducible factor 1-alphaHomo sapiens (human)
cellular response to interleukin-1Hypoxia-inducible factor 1-alphaHomo sapiens (human)
cellular response to hypoxiaHypoxia-inducible factor 1-alphaHomo sapiens (human)
dopaminergic neuron differentiationHypoxia-inducible factor 1-alphaHomo sapiens (human)
mesenchymal cell apoptotic processHypoxia-inducible factor 1-alphaHomo sapiens (human)
hypoxia-inducible factor-1alpha signaling pathwayHypoxia-inducible factor 1-alphaHomo sapiens (human)
cellular response to virusHypoxia-inducible factor 1-alphaHomo sapiens (human)
positive regulation of cytokine production involved in inflammatory responseHypoxia-inducible factor 1-alphaHomo sapiens (human)
positive regulation of mitophagyHypoxia-inducible factor 1-alphaHomo sapiens (human)
negative regulation of miRNA transcriptionHypoxia-inducible factor 1-alphaHomo sapiens (human)
positive regulation of miRNA transcriptionHypoxia-inducible factor 1-alphaHomo sapiens (human)
negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathwayHypoxia-inducible factor 1-alphaHomo sapiens (human)
regulation of aerobic respirationHypoxia-inducible factor 1-alphaHomo sapiens (human)
negative regulation of reactive oxygen species metabolic processHypoxia-inducible factor 1-alphaHomo sapiens (human)
regulation of protein neddylationHypoxia-inducible factor 1-alphaHomo sapiens (human)
negative regulation of mesenchymal cell apoptotic processHypoxia-inducible factor 1-alphaHomo sapiens (human)
regulation of transcription by RNA polymerase IIHypoxia-inducible factor 1-alphaHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (23)

Processvia Protein(s)Taxonomy
DNA-binding transcription factor activity, RNA polymerase II-specificHypoxia-inducible factor 1-alphaHomo sapiens (human)
sequence-specific DNA bindingHypoxia-inducible factor 1-alphaHomo sapiens (human)
RNA polymerase II transcription regulatory region sequence-specific DNA bindingHypoxia-inducible factor 1-alphaHomo sapiens (human)
RNA polymerase II cis-regulatory region sequence-specific DNA bindingHypoxia-inducible factor 1-alphaHomo sapiens (human)
DNA-binding transcription factor activity, RNA polymerase II-specificHypoxia-inducible factor 1-alphaHomo sapiens (human)
cis-regulatory region sequence-specific DNA bindingHypoxia-inducible factor 1-alphaHomo sapiens (human)
DNA-binding transcription activator activityHypoxia-inducible factor 1-alphaHomo sapiens (human)
DNA-binding transcription repressor activityHypoxia-inducible factor 1-alphaHomo sapiens (human)
transcription coactivator bindingHypoxia-inducible factor 1-alphaHomo sapiens (human)
DNA-binding transcription activator activity, RNA polymerase II-specificHypoxia-inducible factor 1-alphaHomo sapiens (human)
p53 bindingHypoxia-inducible factor 1-alphaHomo sapiens (human)
DNA-binding transcription factor activityHypoxia-inducible factor 1-alphaHomo sapiens (human)
protein bindingHypoxia-inducible factor 1-alphaHomo sapiens (human)
nuclear receptor bindingHypoxia-inducible factor 1-alphaHomo sapiens (human)
enzyme bindingHypoxia-inducible factor 1-alphaHomo sapiens (human)
protein kinase bindingHypoxia-inducible factor 1-alphaHomo sapiens (human)
protein domain specific bindingHypoxia-inducible factor 1-alphaHomo sapiens (human)
ubiquitin protein ligase bindingHypoxia-inducible factor 1-alphaHomo sapiens (human)
histone deacetylase bindingHypoxia-inducible factor 1-alphaHomo sapiens (human)
protein heterodimerization activityHypoxia-inducible factor 1-alphaHomo sapiens (human)
Hsp90 protein bindingHypoxia-inducible factor 1-alphaHomo sapiens (human)
RNA polymerase II-specific DNA-binding transcription factor bindingHypoxia-inducible factor 1-alphaHomo sapiens (human)
E-box bindingHypoxia-inducible factor 1-alphaHomo sapiens (human)
transcription regulator activator activityHypoxia-inducible factor 1-alphaHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (12)

Processvia Protein(s)Taxonomy
nucleusHypoxia-inducible factor 1-alphaHomo sapiens (human)
nucleoplasmHypoxia-inducible factor 1-alphaHomo sapiens (human)
cytoplasmHypoxia-inducible factor 1-alphaHomo sapiens (human)
cytosolHypoxia-inducible factor 1-alphaHomo sapiens (human)
nuclear bodyHypoxia-inducible factor 1-alphaHomo sapiens (human)
nuclear speckHypoxia-inducible factor 1-alphaHomo sapiens (human)
motile ciliumHypoxia-inducible factor 1-alphaHomo sapiens (human)
axon cytoplasmHypoxia-inducible factor 1-alphaHomo sapiens (human)
chromatinHypoxia-inducible factor 1-alphaHomo sapiens (human)
euchromatinHypoxia-inducible factor 1-alphaHomo sapiens (human)
protein-containing complexHypoxia-inducible factor 1-alphaHomo sapiens (human)
RNA polymerase II transcription regulator complexHypoxia-inducible factor 1-alphaHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (4)

Assay IDTitleYearJournalArticle
AID1427246Antiproliferative activity against human MDA-MB-468 cells after 72 hrs under hypoxic condition by MTT assay2017Bioorganic & medicinal chemistry, 03-15, Volume: 25, Issue:6
Synthesis and evaluation of N-(benzofuran-5-yl)aromaticsulfonamide derivatives as novel HIF-1 inhibitors that possess anti-angiogenic potential.
AID1427245Antiproliferative activity against human MDA-MB-231 cells after 72 hrs under hypoxic condition by MTT assay2017Bioorganic & medicinal chemistry, 03-15, Volume: 25, Issue:6
Synthesis and evaluation of N-(benzofuran-5-yl)aromaticsulfonamide derivatives as novel HIF-1 inhibitors that possess anti-angiogenic potential.
AID1427244Antiproliferative activity against human MCF7 cells after 72 hrs under hypoxic condition by MTT assay2017Bioorganic & medicinal chemistry, 03-15, Volume: 25, Issue:6
Synthesis and evaluation of N-(benzofuran-5-yl)aromaticsulfonamide derivatives as novel HIF-1 inhibitors that possess anti-angiogenic potential.
AID1427242Inhibition of HIF-1alpha (unknown origin) transcriptional activity expressed in human MCF7 cells after 24 hrs under hypoxic condition by HRE luciferase reporter gene assay2017Bioorganic & medicinal chemistry, 03-15, Volume: 25, Issue:6
Synthesis and evaluation of N-(benzofuran-5-yl)aromaticsulfonamide derivatives as novel HIF-1 inhibitors that possess anti-angiogenic potential.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (52)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's10 (19.23)29.6817
2010's24 (46.15)24.3611
2020's18 (34.62)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 35.21

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index35.21 (24.57)
Research Supply Index3.97 (2.92)
Research Growth Index4.87 (4.65)
Search Engine Demand Index44.62 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (35.21)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews6 (11.54%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other46 (88.46%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]