hypoxia signaling pathway

Pathways Recommended:	MAPK/ERK Pathway Neuronal Signaling JAK/STAT Signaling

By Targets:	HIF/HIF Prolyl-Hydroxylase (6) Akt (3) Apoptosis (7) Autophagy (1) Bcl-2 Family (1) Caspase (5) CaSR (1) E1/E2/E3 Enzyme (1) ERK (1) IKK (1) Integrin (1) Interleukin Related (1) JNK (1) Lactate Dehydrogenase (1) Ligands for E3 Ligase (1) MDM-2/p53 (1) MEK (1) mGluR (1) mTOR (1) Natriuretic Peptide Receptor (NPR) (1) NF-κB (1) p38 MAPK (3) PERK (2) PGC-1α (1) PI3K (1) PPAR (2) Raf (1) Reactive Oxygen Species (ROS) (2) Reference Standards (2) TNF Receptor (1)
By Research Areas:	Cancer (5) Cardiovascular Disease (4) Inflammation/Immunology (3) Metabolic Disease (2) Neurological Disease (4)

Targets Recommended: Tissue Factor Pathway Inhibitor (TFPI) RGS Protein HIF/HIF Prolyl-Hydroxylase

Cat. No.	Product Name	Target	Research Areas	Chemical Structure

HY-N0265

Asperosaponin VI 3 Publications Verification Akebia saponin D	Caspase Apoptosis PERK p38 MAPK Akt HIF/HIF Prolyl-Hydroxylase PPAR	Cardiovascular Disease Neurological Disease
Asperosaponin VI is a saponin component from Dipsacus asper. Asperosaponin VI induces osteoblast differentiation through the BMP-2/p38 and ERK1/2 signaling pathways. Asperosaponin VI protects against hypoxia-induced cardiomyocyte apoptosis by activating the PI3K/Akt and CREB pathways. Additionally, Asperosaponin VI also has antidepressant and wound-healing-promoting activities .

HY-156106

VHL-IN-1	HIF/HIF Prolyl-Hydroxylase Ligands for E3 Ligase E1/E2/E3 Enzyme	Cancer
VHL-IN-1 (Compound 30) is an E3 ligase VHL inhibitor with a K_d value of 37 nM. VHL-IN-1 blocks VHL-mediated ubiquitination and degradation of HIF-1α. VHL-IN-1 stabilizes the protein levels of HIF-1α and hydroxylated HIF-1α, and induces the transcriptional activity of HIF-1α. VHL-IN-1 can be used for PROTAC development. VHL-IN-1 is applicable for cancer research .

HY-15672

FM19G11	HIF/HIF Prolyl-Hydroxylase	Neurological Disease Cancer
FM19G11 is a hypoxia-inducible factor-1-alpha (HIF-1α) inhibitor, and it inhibits hypoxia-induced luciferase activity with an IC₅₀ of 80 nM in HeLa cells. FM19G11 modulates other signaling pathways, including mTOR and PI3K/Akt/eNOS, when the HIF-1α pathway is inactivated under normoxic conditions .

HY-11095

NPS 2390	mGluR CaSR PI3K Akt mTOR Autophagy Apoptosis Bcl-2 Family Caspase	Cardiovascular Disease Neurological Disease
NPS 2390 is an allosteric antagonist of calcium-sensing receptor (CaSR) and mGluR1/5. NPS 2390 inhibits the PI3K/Akt/mTOR signaling pathway, reduces hypoxia-induced intracellular calcium elevation, decreases the expression of autophagy (autophagy) proteins, regulates the expression of phenotypic marker proteins, and inhibits the proliferation of pulmonary artery smooth muscle cells. NPS 2390 attenuates the endogenous apoptosis (apoptosis) pathway, increases the expression level of Bcl-2, downregulates the expression levels of Bax, cytochrome c and caspase-3, alleviates cerebral edema and improves neurological function in rat models. NPS 2390 can be used in studies related to hypoxic pulmonary hypertension, traumatic brain injury, stroke and pain .

HY-N5073

Vitexin-4''-O-glucoside 4''-O-Glucosylvitexin	JNK p38 MAPK Interleukin Related TNF Receptor Caspase Lactate Dehydrogenase Apoptosis	Cardiovascular Disease Metabolic Disease
Vitexin-4''-O-glucoside (4''-O-Glucosylvitexin) is an orally active natural flavonoid component with multiple pharmacological effects including antioxidation, anti-inflammation, cytoprotection and anti-apoptosis. Vitexin-4''-O-glucoside regulates the MAPK signaling pathway by downregulating the phosphorylation levels of JNK and p38, thereby blocking endoplasmic reticulum stress responses. Vitexin-4''-O-glucoside alleviates oxidative stress by reducing MDA content and upregulating the activities of SOD and CAT, attenuates inflammation by downregulating the expressions of inflammatory factors TNF-α, IL-1β and IL-6, and also reduces LDH release and inhibits caspase-3 activation. Vitexin-4''-O-glucoside effectively improves drug-induced acute liver injury and exerts significant protective effects against myocardial hypoxia/reoxygenation injury. Vitexin-4''-O-glucoside can be used in studies on acute liver injury, cardiovascular diseases and myocardial hypoxia-reoxygenation injury .

HY-N13009

MO-2097	Raf HIF/HIF Prolyl-Hydroxylase ERK MEK Reactive Oxygen Species (ROS) Apoptosis Caspase	Cancer
MO-2097 is a RAF-1/HIF-1α inhibitor. MO-2097 induces RAF-1 destabilization, leading to a reduction in EMT-associated transcription factors and mesenchymal markers. MO-2097 inhibits HIF-1a protein expression mediated by hnRNPA2B1 under hypoxic and mimetic hypoxia. MO-2097 induces mitochondrial ROS, which leads to apoptosis in cells. MO-2097 effectively suppresses colorectal cancer metastasis by inhibiting the RAF/MEK/ERK signaling pathway. MO-2097 attenuates tumor growth in a xenograft HCT116 cell mouse model. MO-2097 can be used for the study of colorectal cancer .

HY-N0265R

Asperosaponin VI (Standard) Akebia saponin D (Standard)	Reference Standards Caspase Apoptosis PERK Akt p38 MAPK HIF/HIF Prolyl-Hydroxylase PPAR	Cardiovascular Disease Neurological Disease
Asperosaponin VI (Standard) is the analytical standard of Asperosaponin VI. This product is intended for research and analytical applications. Asperosaponin VI is a saponin component from Dipsacus asper. Asperosaponin VI induces osteoblast differentiation through the BMP-2/p38 and ERK1/2 signaling pathways. Asperosaponin VI protects against hypoxia-induced cardiomyocyte apoptosis by activating the PI3K/Akt and CREB pathways. Additionally, Asperosaponin VI also has antidepressant and wound-healing-promoting activities .

HY-P10988

LVTX-8	Apoptosis MDM-2/p53 Integrin	Cancer
LVTX-8 is a peptide toxin, exacted from Lycosa vittata. LVTX-8 has potent anticancer and and anti-metastasis activities towards lung cancer with strong cytotoxicity. LVTX-8 significantly induces apoptosis and inhibits the proliferation, invasion and migration of lung cancer cells through P53 hypoxia pathways and integrin signaling. LVTX-8 significantly inhibits the tumor growth and metastasis in A549/H460 xenograft mice model .

HY-175521

HIF-1α-IN-8	HIF/HIF Prolyl-Hydroxylase IKK NF-κB Apoptosis Reactive Oxygen Species (ROS)	Inflammation/Immunology
HIF-1α-IN-8 is an orally active HIF-1α inhibitor, with an IC₅₀ of 2.02 μM. HIF-1α-IN-8 significantly suppresses the expression of inflammation factors of IL-6 and NO, reduces hypoxia-induced ROS production and apoptosis in C8-D1A cells. HIF-1α-IN-8 inhibits HIF-1α/IKKα/NF-κB signaling pathway and reduces the expression of blood-brain barrier permeability-related proteins. HIF-1α-IN-8 reduces brain water content and oxidative stress level in mice with high altitude cerebral edema (HACE) model. HIF-1α-IN-8 can be used for the study of high altitude cerebral edema (HACE) .

HY-P10869

dCNP 1 Publications Verification	Natriuretic Peptide Receptor (NPR)	Inflammation/Immunology Cancer
dCNP binds to NPR-B/C receptor, activates cGMP signaling pathway, and regulates vascular function. dCNP exhibits anti-hypoxia property through downregulation of hypoxia-related genes expressions like HIF1α and HIF2α. dCNP inhibits the induction of tumor stroma and exhibits anti-fibrosis activity. dCNP upregulates CTLs, NK cells, and conventional type 1 dendritic cells in tumors, and activates immune responses .

HY-N0272R

Eleutheroside E (Standard)	Reference Standards Others	Inflammation/Immunology
Eleutheroside E (Standard) is the analytical standard of Eleutheroside E. This product is intended for research and analytical applications. Eleutheroside E is an important component of Eleutheroside and has antioxidant, anti-fatigue, anti-inflammatory, antibacterial, immunomodulatory and cardioprotective effects. Eleutheroside E may inhibit the MAPK signaling pathway, thereby inhibiting H/R-induced NF-κB activation and oxidative stress, reducing metabolic reprogramming, and protecting myocardium from ischemia-reperfusion (I/R) injury. Eleutheroside E also counteracts the effects of high altitude hypobaric hypoxia (HAHI) by inhibiting inflammation and pyroptosis .

HY-183094

AM73	PGC-1α	Metabolic Disease
AM73 is a PGC-1α1 stabilizer. AM73 increases the expression levels of Ucp1 and Cidea in brown adipocytes, and enhances basal mitochondrial respiration and uncoupled respiration. AM73 regulates hypoxia, brown adipocyte differentiation, carbohydrate metabolism and insulin signaling pathways in brown adipocytes. AM73 alters the thermogenic process of white adipocytes. AM73 is applicable to the research of obesity and related metabolic disorders .

Cat. No.	Product Name

HY-L045

Oxygen Sensing Compound Library	4,097 compounds
Oxygen homeostasis regulation is the most fundamental cellular process for adjusting physiological oxygen variations, and its irregularity leads to various human diseases, including cancer. Hypoxia is closely associated with cancer development, and hypoxia/oxygen-sensing signaling plays critical roles in the modulation of cancer progression. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis. A variety of HF-1 target genes have been identified thus far which encode proteins that play key roles in critical developmental and physiological processes including angiogenesis/vascular remodeling, erythropoiesis, glucose transport, glycolysis, iron transport, and cell proliferation/survival. HIF-1 is a heterodimeric transcription factor consisting of a constitutively expressed β-subunit and an oxygen-regulated α-subunit. The unique feature of HIF-1 is the regulation of HIF-1α expression and activity based upon the cellular O₂ concentration. Under normoxic conditions, hydroxylation of HIF-1α on these different proline residues is essential for HIF proteolytic degradation by promoting interaction with the von Hippel-Lindau tumor-suppressor protein (pVHL) through hydrogen bonding to the hydroxyproline-binding pocket in the pVHL β-domain. As oxygen levels decrease, hydroxylation of HIF decreases; HIF-1α then no longer binds pVHL, and becomes stabilized, allowing more of the protein to translocate to the cell’s nucleus, where it acts as a transcription factor, upregulating (often within minutes) the production of proteins that stimulate blood perfusion in tissues and thus tissue oxygenation. MCE offers a unique collection of 4,097 oxygen sensing related compounds targeting HIF/HIF Prolyl-Hydroxylase, MAPK/ERK, PI3K/AKT signaling pathways, etc. MCE Oxygen Sensing Compound Library is a useful tool to study hypoxia, oxidative stress and discover new anti-cancer drugs.

Oxygen Sensing Compound Library

4,097 compounds

Oxygen homeostasis regulation is the most fundamental cellular process for adjusting physiological oxygen variations, and its irregularity leads to various human diseases, including cancer. Hypoxia is closely associated with cancer development, and hypoxia/oxygen-sensing signaling plays critical roles in the modulation of cancer progression.

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis. A variety of HF-1 target genes have been identified thus far which encode proteins that play key roles in critical developmental and physiological processes including angiogenesis/vascular remodeling, erythropoiesis, glucose transport, glycolysis, iron transport, and cell proliferation/survival.

HIF-1 is a heterodimeric transcription factor consisting of a constitutively expressed β-subunit and an oxygen-regulated α-subunit. The unique feature of HIF-1 is the regulation of HIF-1α expression and activity based upon the cellular O₂ concentration. Under normoxic conditions, hydroxylation of HIF-1α on these different proline residues is essential for HIF proteolytic degradation by promoting interaction with the von Hippel-Lindau tumor-suppressor protein (pVHL) through hydrogen bonding to the hydroxyproline-binding pocket in the pVHL β-domain. As oxygen levels decrease, hydroxylation of HIF decreases; HIF-1α then no longer binds pVHL, and becomes stabilized, allowing more of the protein to translocate to the cell’s nucleus, where it acts as a transcription factor, upregulating (often within minutes) the production of proteins that stimulate blood perfusion in tissues and thus tissue oxygenation.

MCE offers a unique collection of 4,097 oxygen sensing related compounds targeting HIF/HIF Prolyl-Hydroxylase, MAPK/ERK, PI3K/AKT signaling pathways, etc. MCE Oxygen Sensing Compound Library is a useful tool to study hypoxia, oxidative stress and discover new anti-cancer drugs.

HY-L064

Glutamine Metabolism Compound Library	1,730 compounds
Glutamine is an important metabolic fuel that helps rapidly proliferating cells meet the increased demand for ATP, biosynthetic precursors, and reducing agents. Glutamine Metabolism pathway involves the initial deamination of glutamine by glutaminase(GLS), yielding glutamate and ammonia. Glutamate is converted to the TCA cycle intermediate α-ketoglutarate (α-KG) by either glutamate dehydrogenase (GDH) or by the alanine or aspartate transaminases (TAs), to produce both ATP and anabolic carbons for the synthesis of amino acids, nucleotides and lipids. During periods of hypoxia or mitochondrial dysfunction, α-KG can be converted to citrate in a reductive carboxylation reaction catalyzed by IDH2. The newly formed citrate exits the mitochondria where it is used to synthesize fatty acids and amino acids and produce the reducing agent, NADPH. Cancer cells display an altered metabolic circuitry that is directly regulated by oncogenic mutations and loss of tumor suppressors. Mounting evidence indicates that altered glutamine metabolism in cancer cells has critical roles in supporting macromolecule biosynthesis, regulating signaling pathways, and maintaining redox homeostasis, all of which contribute to cancer cell proliferation and survival. Thus, intervention in glutamine metabolic processes could provide novel approaches to improve cancer treatment. MCE owns a unique collection of 1,730 compounds targeting the mainly proteins and enzymes involved in glutamine metabolism pathway. Glutamine Metabolism compound library is a useful tool for intervention in glutamine metabolic processes.

Glutamine Metabolism Compound Library

1,730 compounds

Glutamine is an important metabolic fuel that helps rapidly proliferating cells meet the increased demand for ATP, biosynthetic precursors, and reducing agents. Glutamine Metabolism pathway involves the initial deamination of glutamine by glutaminase(GLS), yielding glutamate and ammonia. Glutamate is converted to the TCA cycle intermediate α-ketoglutarate (α-KG) by either glutamate dehydrogenase (GDH) or by the alanine or aspartate transaminases (TAs), to produce both ATP and anabolic carbons for the synthesis of amino acids, nucleotides and lipids. During periods of hypoxia or mitochondrial dysfunction, α-KG can be converted to citrate in a reductive carboxylation reaction catalyzed by IDH2. The newly formed citrate exits the mitochondria where it is used to synthesize fatty acids and amino acids and produce the reducing agent, NADPH.

Cancer cells display an altered metabolic circuitry that is directly regulated by oncogenic mutations and loss of tumor suppressors. Mounting evidence indicates that altered glutamine metabolism in cancer cells has critical roles in supporting macromolecule biosynthesis, regulating signaling pathways, and maintaining redox homeostasis, all of which contribute to cancer cell proliferation and survival. Thus, intervention in glutamine metabolic processes could provide novel approaches to improve cancer treatment.

MCE owns a unique collection of 1,730 compounds targeting the mainly proteins and enzymes involved in glutamine metabolism pathway. Glutamine Metabolism compound library is a useful tool for intervention in glutamine metabolic processes.

Cat. No.	Product Name	Target	Research Area