HIF-PH

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.

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

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

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.

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.

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.

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

Chlorogenic acid is a natural phenol found in honeysuckle. Chlorogenic acid has a wide range of biological activities including anti-inflammatory, antioxidant, antitumor, antimicrobial, and neuroprotective.

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.

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

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

Ethyl 3,4-dihydroxybenzoate (EDHB): a prolyl hydroxylase inhibitor attenuates acute hypobaric hypoxia mediated vascular leakage in brain.

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.

Chloramphenicol (Chloromycetin) is a broad-spectrum antibiotic that inhibits the biosynthesis of bacterial proteins. Chloramphenicol acts primarily on the 50S subunit of the bacterial 70S ribosome and is active against peptidyltransferases, inhibiting the formation of peptide bonds.

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.

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 inhibitor of HIF-2α with a dissociation constant (Kd) of less than 50 nM (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.

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.

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).

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

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.

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

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.

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

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

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.

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.

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

2,4-DPD is competitive inhibitor of the oxygen-sensing enzyme HIF-α prolyl hydroxylase (HIF-PH)

HNHA is an inhibitor of HDAC.

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

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

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.

HIF-2a translation inhibitor is a potent HIF-2α translation inhibitor with IC50=5 μM that inhibits constitutive and hypoxia-induced HIF-2α protein expression. Among them, HIF-2α-IN-4 associates the 5'UTR iron response element with oxygen sensing.

E3330 is a potent and selective APE1(Ref-1) inhibitor, which suppressed NF-kappa B DNA-binding activity.

JNJ-42041935 (HIF-PHD Inhibitor II) is a potent (pKi = 7.3-7.9), 2-oxoglutarate competitive, reversible, and selective inhibitor of PHD enzymes.

FG-2216 (YM-311) is a potent HIF-prolyl hydroxylase inhibitor for the PDH2 enzyme (IC50: 3.9 uM); orally bioavailable and induced reversible and significant Epo induction in vivo.

M1001 is a HIF-2α agonist.

IOX4 is a potent PHD2 inhibitor (IC50 = 1.6 nM)

Roxadustat-d5 is intended for use as an internal standard for the quantification of roxadustat by GC- or LC-MS. Roxadustat is an inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PH; IC50s = 1.4, 1.26, and 1.32 µM for HIF-PH1, HIF-PH2, and HIF-PH3, respectively). It is selective for HIF-PH over other 2-oxoglutarate-dependent dioxygenases, including lysine-specific demethylase 5A (KDM5A), KDM5B, -5C, -5D, and -6B (IC50s = >100 µM for all). Roxadustat (10-200 µM) stabilizes HIF-1α and HIF-2α in Hep3B hepatocellular carcinoma cells. It increases levels of secreted erythropoietin in Hep3B cells in a concentration-dependent manner and increases erythropoiesis in rats when administered at doses of 25 and 50 mg/kg. Roxadustat reverses anemia in a rat model of chronic inflammation induced by peptidoglycan-polysaccharide, as well as a rat model of chronic kidney disease induced by 5/6 nephrectomy. It reduces tumor growth and increases survival in a murine Lewis lung carcin......