hypoxia-inducible factors

PX-478 is a HIF-1α inhibitor with selectivity, oral activity, and blood-brain barrier permeability. PX-478 has antitumor activity and also protects pancreatic β-cell function in diabetes mellitus and is used in type 2 diabetes mellitus research.

Deferoxamine Mesylate (DFOM) is an iron chelator and ferroptosis inhibitor. Deferoxamine Mesylate binds free iron into a stable complex and reduces iron accumulation. Deferoxamine Mesylate up-regulates HIF-1α levels and induces apoptosis.

Hydroxycitric acid tripotassium hydrate (Potassium citrate monohydrate) effectively inhibits stones formation and also inhibits HIF, and has antioxidation, anti-inflammation, and anti-tumor effects. Hydroxycitric acid tripotassium hydrate(Potassium citrate monohydrate) (Potassium citrate monohydrate) is the major active ingredient of Garcinia cambogia and a derivative of citric acid. Hydroxycitric acid tripotassium hydrate(Potassium citrate monohydrate) competitively inhibits ATP citrate lyase with weight loss benefits.

Glucosamine (Chitosamine) is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids. Supplemental glucosamine may help to rebuild cartilage and treat arthritis.

AKB-6899 is an inhibitor of prolyl hydroxylase domain 3 (PHD3) and increases the soluble form of the VEGF receptor (sVEGFR-1) production from GM-CSF-treated macrophages. AKB-6899 leads to stabilization of HIF-2α which induces sVEGFR-1 production from tumor-associated macrophages and decreases tumor growth.

1,4-DPCA is an inhibitor of prolyl-hydroxylase with an IC50 of 2.4 µM for collagen hydroxylation in human foreskin fibroblasts and 60 μM for factor inhibiting HIF (FIH).

PT-2385 is a selective HIF-2α inhibitor (Kd<50 nM).

1. Deoxyshikonin (Arnebin 7) may be a new drug candidate for wound healing and treatment of lymphatic diseases. 2. Deoxyshikonin enhances the ability of human dermal lymphatic microvascular endothelial cells (HMVEC-dLy) to undergo time-dependent in vitro cord formation. 3. Deoxyshikonin and dodecyl gallate show significantly synergic antimicrobial activity with penicillin in vivo and in vitro, and can effectively reduce nasopharyngeal and lung colonization caused by different penicillin-resistant pneumococcal serotypes.

IDF-11774 is a HIF-1 inhibitor.It reduces hif-1α HRE luciferase activity (IC50 = 3.65 μM).

BAY 87-2243 is a potent and selective inhibitor of hypoxia-inducible factor-1 (HIF-1).

Chlorogenic acid, as a major phenolic compound in honeysuckle, possesses potential antioxidant, antibacterial, anti-inflammatory, and anticancer activities. It can be utilized in research related to the treatment of advanced cancer and impaired glucose tolerance.

DMOG (Dimethyloxalylglycine), an antagonist of the α-ketoglutarate cofactor, is an inhibitor for HIF prolyl hydroxylase.

LW6 (HIF-1α inhibitor) is a novel HIF-1 inhibitor.

KC7F2 is a potent HIF-1 pathway inhibitor with potential anti-cancer activity.

Molidustat (BAY 85-3934)(BAY-85-3934), an inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase (PH), stimulates erythropoietin (EPO) production and the formation of red blood cells.

Roxadustat (FG-4592) is an orally bioavailable, hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), with potential anti-anemic activity.

Chloramphenicol (Chloromycetin), a broad-spectrum antibiotic, blocks bacterial protein synthesis.

1. Oroxylin A (Baicalein 6-methyl ether) has various anti-tumor effects including apoptosis, cell cycle arrest, drug-resistant reversion. 2. Oroxylin A possesses abilities of inhibiting the ATRA-induced IL-6 production via modulation of LAP/LIP/CHOP in leukemia cell lines, which could providing a therapeutic strategy for RAS. 3. Oroxylin A inhibits UCP2s triggers the MPTP opening, and promotes the apoptosis in CaCo-2 cells; uncoupling protein 2 plays a key role in mitochondrial apoptotic pathway. 4. Oroxylin A inhibits N1ICD translocating to the nucleus and binding to epithelial-mesenchymal transition-related transcription factor Snail, thus suppressing the invasion and migration of MCF-7 cells. 5. Oroxylin A improves the sensitivity of K562/ADM cells by increasing apoptosis in leukemic cells and decreasing the expression of CXCR4 and PI3K/Akt/NF-κB pathway, and probably served as a most promising agent for CML treatment.

AKBA (3-O-Acetyl-11-keto-beta-boswellic acid), a natural component from frankincense, is a novel activator of Nrf2.

Minocycline hydrochloride (Minocycline HCl) is a tetracycline antibiotic with excellent absorption and tissue penetration that is used for several bacterial infections as well as treatment of acne. Minocycline hydrochloride can cause both an acute hepatitis-like syndrome occurring within 1 to 3 months of starting therapy or a more insidious chronic hepatitis with autoimmune features typically after long-term treatment.

Adaptaquin is an inhibitor of the hypoxia-inducing factor prolyl hydroxylase (HIF-PH) [1] [2].

Tert-butyl 4-[[1-[(4-chlorophenyl)methyl]-3-hydroxy-2-oxopyridin-4-yl]methyl]piperazine-1-carboxylate inhibit of human recombinant EGLN-1 as substrate after 20 mins by mass spectrophotometric analysis.

HIF-2α-IN-2 is a hypoxia-inducible factor (HIF-2α) inhibitor (IC50: 16 nM in scintillation proximity assay).

EHP-101 (VCE-004.8) is a specific dual agonist of PPARγ and CB2 receptor with potent anti-inflammatory activity. EHP-101 attenuates adipogenesis and prevents diet-induced obesity.

This novel compound is an orally bioavailable antagonist of P2X3/P2X2/3 receptors, exhibiting potent activity with a pIC50 of 8 in both human and rat, and a pIC50 of 7.3 specifically for the human P2X2/3 receptor. It demonstrates high brain penetration, evidenced by a brain to plasma ratio of 6, and effectively blocks agonist-evoked intracellular Ca2+ flux and inward currents within the nanomolar range (10 nM to 1 µM) in cell lines that express human P2X3 and P2X2/3 receptors recombinantly. The compound also shows favorable pharmacokinetic properties, with a half-life (t1/2) of 1.63 hours and a time to reach maximum concentration (Tmax) of 30 minutes.

Vadadustat is a novel, titratable, oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor in development for the treatment of anemia.

Amifostine trihydrate (WR2721) is the first approved radioprotective drug, used to decrease the risk of kidney problems caused by treatment with cisplatin.

MK-8617 is an orally available HIF PHD1 3 pan-inhibitor, inhibiting PHD1/2/3 (IC50: 1.0/1.0/14 nM).

ZINC13466751 is a potent HIF-1α/von Hippel-Lindau interaction inhibitor(IC50 of 2.0 µM).

Enarodustat (JTZ-951) is an orally active factor inhibitor of prolyl hydroxylase (EC50: 0.22 μM) and has the potential for renal anemia treatment.

Glucosamine sulfate (D-Glucosaminesulfate) was extracted from synthetic product;Store the product in sealed, cool and dry condition.

Glucosamine hydrochloride (Chitosamine hydrochloride) is commonly used as a treatment for osteoarthritis, although its acceptance as a medical therapy varies.

Albendazole (SKF-62979) is used as a drug indicated for the treatment of a variety of worm infestations.

Citric acid trilithium salt tetrahydrate (Lithium citrate tribasic tetrahydrate) , the active component of Lithium, is a medicine used in the therapy of psychiatric disease. It has shown the effects of signaling pathways and metabolic in the brain based on the particular disease and clinical condition model. According to the reports, Citric acid trilithium salt tetrahydrate was used as a mood stabilizer when treating bipolar mood disorders (BD) and lower the risk of self-harm in BD patient. In addition,Citric acid trilithium salt tetrahydrate has been the choice drug in the therapy of acute manic episodes.Citric acid trilithium salt tetrahydrate also could dissolve uric acid crystals in urine achieved from patients with gout. Besides,Citric acid trilithium salt tetrahydrate have some dose-dependent side-effects. The the main side-effects of Lithium Citrate is the tendency to inhibit the prostatic acid phosphatase enzyme (PAP), which result in the accumulation of PAP.

1. Fraxinellone significantly reduced weight loss and diarrhea in mice and alleviated the macroscopic and microscopic signs of the disease. 2. Fraxinellone exhibited a variety of insecticidal activities including feeding-deterrent activity, inhibition of growth, and larvicidal activity. 3. Fraxinellone has effect in the midgut metabolism of Mythimna separata (M. separata), via protease (especially the weak alkaline trypsin-like enzyme), carboxylesterase and glutathione S-transferase.

SYP-5 is a novel inhibitor of HIF-1, suppresses tumor cells invasion and angiogenesis.

TP-0463518 is a highly potent HIF prolyl hydroxylase (PHD) inhibitor (IC50s: 13 nM and 18 nM for human and rat PHD2, respectively).

Oltipraz (RP 35972) is a synthetic dithiolethione with potential chemopreventive and anti-angiogenic properties. Oltipraz induces phase II detoxification enzymes, such as glutathione S transferase (GST) and NAD(P)H: quinone oxidoreductase 1 (NQO1). The induction of detoxification enzymes enhances the detoxification of certain cancer-causing agents, thereby enhancing their elimination and preventing carcinogen-induced DNA damages. Although the exact mechanism through which the anti-angiogenesis effect remains to be fully elucidated, oltipraz maybe able to modulate the expression of a number of angiogenic factors, thereby blocking the sustained and focal neovascularization in multiple tumor cell types.

Panaxadiol (20(R)-Panaxadiol) is a novel antitumor agent extracted from the Chinese medical herb Panax ginseng.

Amifostine (Ethyol) anhydrous is a cytoprotective agent, acts as a free radical scavenging activity.

PT2399 shows effective antitumor activity in vivo. PT2399 is an effective and selective HIF-2α antagonist, which directly binds to the HIF-2α PAS B domain (IC50: 6 nM).

Daprodustat (GSK1278863) is a HIF-prolyl hydroxylase inhibitor.

Hydralazine hydrochloride (Apresoline) is the hydrochloride salt of hydralazine, a phthalazine derivative with antihypertensive and potential antineoplastic activities. Hydralazine alters intracellular calcium release and interferes with smooth muscle cell calcium influx, resulting in arterial vasodilatation. This agent also inhibits the phosphorylation of myosin protein and chelation of trace metals required for smooth muscle contraction, resulting in an increase in heart rate, stroke volume, and cardiac output. In addition to its cardiovascular effects, hydralazine inhibits DNA methyltransferase, which may result in inhibition of DNA methylation in tumor cells.

HNHA is an inhibitor of HDAC.

Dencichine (ODAP) is a neurotoxic agent. Dencichine is a haemostatic agent, the hemostatic effect relates to modulation of the coagulation system, platelet aggregation and fibrinolytic system. It has renoprotective effect, it could significantly prevent the progression of diabetic nephropathy possibly attribute to down-regulation of the TGF-β/Smad pathway and rebalance the deposition and degradation of ECM proteins.

IOX2 (IOX 2) is a selective inhibitor of the Hypoxia Inducible Factor (HIF) Prolyl-Hydroxylases (PHD); active in cells with the IC50 value of 21 nM for PHD2/ELGN-1 and no inhibition at FIH (20uM).

HIF1-IN-3 (Benzenepropanamide, N-[(8-hydroxy-7-quinolinyl)(4-methoxyphenyl)methyl]-) is an effective inhibitor of HIF-1 (EC50 = 0.9 μM) and can be used in anticancer studies.

GN44028 (N-(2,3-Dihydro-1,4-benzodioxin-6-yl)-1,4-dihydroindeno[1,2-c]pyrazol-3-amine) is a hypoxia-inducible factor inhibitor of (HIF)-1 (IC50: 14 nM). GN44028 inhibits hypoxia-induced HIF-1α transcriptional activity. However, It can not be suppressing HIF-1α mRNA expression, HIF-1α protein accumulation, or HIF-1α/HIF-1β heterodimerization.

Belzutifan (MK-6482) is a potential treatment for clear cell renal cell carcinoma (ccRCC). Belzutifan is an orally active and selective HIF-2α inhibitor (IC50: 9 nM). Belzutifan , as a second-generation HIF-2α inhibitor, increases potency and improves pharmacokinetic profile.

PHD-1-IN-1 is a potent inhibitor of hypoxia-inducible factor prolylhydroxylase domain-1 (PHD-1) enzyme(IC50 = 0.034 μM).