329932-55-0

Usage

Uses

Used in Pharmaceutical Research:
HIF-1alpha/2alpha Inhibitor is used as a research tool for studying the effects of hypoxia-inducible factors on various cellular processes and their role in cancer development and progression.
Used in Cancer Therapy:
HIF-1alpha/2alpha Inhibitor is used as a potential therapeutic agent for targeting hypoxia-inducible factors in cancer cells, with the aim of disrupting their survival and growth mechanisms.
Used in Ependymal Stem Progenitor Cells (epSPCs) Research:
HIF-1alpha/2alpha Inhibitor is used as a compound to study its effects on the self-renewal and proliferation of ependymal stem progenitor cells (epSPCs) in mice, which can provide insights into the role of HIF factors in stem cell biology.
Used in Glioblastoma (GBM) Research:
HIF-1alpha/2alpha Inhibitor is used to study its effects on the O6-methylguanine DNA-methyltransferase (MGMT) expression in glioblastoma (GBM) cells, which can help understand the role of HIF factors in the development and progression of this aggressive brain cancer.
Used in Melanoma Research:
HIF-1alpha/2alpha Inhibitor is used to study its effects on microphthalmia-associated transcription factor (MITF) expression in melanoma cell lines, which can provide insights into the role of HIF factors in melanoma development and progression.
Used in Drug Delivery Systems:
HIF-1alpha/2alpha Inhibitor is used in combination with gold nanoparticles (NPs) to study the effects of FM19G11-loaded gold nanoparticles on various cellular processes, aiming to improve the delivery, bioavailability, and therapeutic outcomes of the compound in cancer treatment.

Biochem/physiol Actions

FM19G11 is an inhibitor of Hypoxia Inducible Factors α (HIFα), reported to affect self-renewal and differentiation of stem cells. Hypoxia-inducible factors (HIFs) are transcription factors that respond to changes in available oxygen in the cellular environment. Among other functions (like angiogenesis), HIFα proteins affect the self-renewal and the differentiation processes of stem cells. FM19G11 inhibits the HIFα proteins that repress the target genes of the two α subunits, in various tumor cell lines as well as in adult and embryonic stem cell (ESC) models.

Upstream product

• 348600-05-5 methyl 3-((2,4-dinitro)benzamido)benzoate 
• 4518-10-9 Methyl 3-aminobenzoate 
• 99-05-8 meta-aminobenzoic acid 
• 906131-02-0 3-((2,4-dinitro)benzamido)benzoic acid 
• 619-41-0 4-(bromoacetyl)toluene 

Relevant academic research and scientific papers

PHARMACEUTICAL COMPOSITION FOR INHIBITING THE TRANSCRIPTION FACTOR INDUCIBLE BY HYPOXIA, MODULATORS OF PATHOLOGICAL PROCESSES OF ANGIOGENESIS, ONCOGENESIS, INFLAMMATION, APOPTOSIS, AND CELLULAR THERAPY

The present invention is included in the field of pharmacology and medical chemistry and relates to novel molecules represented by general formula (I), especially the one called FM19G11, as well as to pharmaceutical compositions containing them. Said pharmacologically optimized compositions are capable of modulating and/or inhibiting the transcription of genes modulated by the hypoxia-inducible transcription factor (HIF) and which are directly and/or indirectly involved in pathological processes related to cancer, inflammation, tissue repair, stem cell differentiation and regenerative therapy. The present invention also relates to a method for the synthesis of said molecules (I) and to the use thereof in the manufacture of a medicament for the treatment of the mentioned pathological processes.

FM19G11, a new hypoxia-inducible factor (HIF) modulator, affects stem cell differentiation status

The biology of the a subunits of hypoxia-inducible factors (HIFα) has expanded from their role in angiogenesis to their current position in the self-renewal and differentiation of stem cells. The results reported in this article show the discovery of FM19G11, a novel chemical entity that inhibits HIFα proteins that repress target genes of the two α subunits, in various tumor cell lines as well as in adult and embryonic stem cell models from rodents and humans, respectively. FM19G11 inhibits at nanomolar range the transcriptional and protein expression of Oct4, Sox2, Nanog, and Tgf-α undifferentiating factors, in adult rat and human embryonic stem cells, FM19G11 activity occurs in ependymal progenitor stem cells from rats (epSPC), a cell model reported for spinal cord regeneration, which allows the progression of oligodendrocyte cell differentiation in a hypoxic environment, has created interest in its characterization for pharmacological research. Experiments using small interfering RNA showed a significant depletion in Sox2 protein only in the case of HIF2α silencing, but not in HIF1α-mediated ablation. Moreover, chromatin immunoprecipitation data, together with the significant presence of functional hypoxia response element consensus sequences in the promoter region of Sox2, strongly validated that this factor behaves as a target gene of HIF2α in epSPCs. FM19G11 causes a reduction of overall histone acetylation with significant repression of p300, a histone acetyltransferase required as a co-factor for HIF-transcription activation. Arrays carried out in the presence and absence of the inhibitor showed the predominant involvement of epigenetic-associated events mediated by the drug.