HIF/HIF Prolyl-Hydroxylase

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).

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.

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.

Notoginsenoside Ft1 is a saponin originally isolated from P. notoginseng with diverse biological activities

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

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

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.

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

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.

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

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

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

PT-2385 is a selective inhibitor of HIF-2α with a dissociation constant (Kd) of less than 50 nM (Kd<50 nM).

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.

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

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.

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.

UNC6934 is a chemical probe targeting the N-terminal PWWP (PWWP1) domain of NSD2.

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

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.

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.

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.

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.

1. β,β-Dimethylacrylshikonin (Dimethylacrylshikonin) is a promising agent for developing an improved strategy for radiotherapy against tumors. (a) Injection of Dimethylacrylshikonin combined with IR treatment significantly suppressed tumor growth of the HCT-116 xenograft. (b) Dimethylacrylshikonin significantly suppressed the growth of H(22) transplantable hepatoma, and induced the activation of caspase-3 . (c) Dimethylacrylshikonin inhibited growth of gastric cancer SGC-791 cells by inducing ERK signaling pathway. 2. Dimethylacrylshikonin inhibits the proliferation of MCF-7 cells in vitro by inducing apoptosis through the downregulation of Bcl-2, upregulation of Bax and partial inactivation of the NF-κB pathway.

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.

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

Annaosanchun (YC-6) is potentially for the treatment of acute ischemic stroke (AIS).

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

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

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

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

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

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

Fenbendazole (Fenbendazol) is an antinematodal benzimidazole used in veterinary medicine.

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

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.

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.

HIF-2α agonist 2 is an HIF-2α agonist with an EC50 value of 1.68 μM for HIF-2α. HIF-2α agonist 2 can promote the stability of the ARNT A B ring in the 3z structure of HIF-2a-ARNT complex without cytotoxicity to 786-o-Reha-Luc cells. HIF-2α agonist 2 can be used in the study of oxygen metabolism and is closely related to the occurrence of cancer.

M1001 is a HIF-2α agonist.

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

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.

Tilorone dihydrochloride, an orally active interferon inducer, exhibits both antineoplastic and anti-inflammatory actions.

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).

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

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.

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

TM6089 is an inhibitor of Prolyl Hydroxylase that stimulates HIF activity without iron chelation, induces angiogenesis, and protects organ against ischemia.