HIF/HIF Prolyl-Hydroxylase

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.

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.

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.

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

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

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.

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.

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.

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

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).

HIF-1α-IN-6 (compound 3s) is a potent inhibitor of HIF-1α, demonstrating IC50 values of 0.6 nM and 53.3 nM in MiaPaCa-2 and MDA-MB-231 cells, respectively. It suppresses HIF-1α expression through the reduction of HIF-1α mRNA levels [1].

HIF-1 alpha (556-574) TFA is a 19-residue fragment of hypoxia-inducible factor-1 (HIF-1), which serves as the master regulator of oxygen homeostasis [1].

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.

PHD-IN-2 (Compound 91), a potent PHD antagonist with an IC50 of less than 5 nM, effectively stimulates erythropoietin synthesis in HEP3B cells with an EC50 of less than 2.5 μM. It is applicable for research purposes across various medical fields, including cardiovascular, metabolic, hematological, pulmonary, kidney, liver, and wound healing disorders, as well as cancer [1].

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.

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

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.

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

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

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

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

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.

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

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.

HIF-1α-IN-2 hydrochloride is a potent HIF-1α inhibitor exhibiting anticancer activity, demonstrated by IC50 values of 28 nM in MDA-MB-231 cells and 15 nM in MiaPaCa-2 cells. It effectively suppresses HIF-1α expression by inhibiting both transcription and protein translation [1].

Axl-IN-16 (Compound 4), an Axl inhibitor, not only suppresses Axl expression and HIF activity but also triggers fruiting body formation in Flammulina velutipes. This compound can be extracted from the fruiting liquid (FL) of Hypholoma lateritium and Hericium erinaceus [1].

HIF-2α-IN-9 (compound 35r) serves as an HIF-2α inhibitor, effectively suppressing VEGF-A with an IC50 of 305 nM, and modulating growth-promoting genes within tumor cells while reactivating macrophage-mediated tumor immunity [1].

VHL-IN-1 (compound 30), a ubiquitin E3 ligase von Hippel-Lindau (VHL) inhibitor with a dissociation constant (Kd) of 37 nM, potently stabilizes HIF-1α and enhances its transcriptional activity. It shows promise for applications as a HIF-1α stabilizer and for the degradation of proteolytically targeted chimeras (PROTACs) [1].

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

Tilorone dihydrochloride is an orally active interferon inducer, and has antineoplastic and anti-inflammatory actions.

Angiogenesis Agent 1 (Compound C-31), a glycoside analogue derived from salidroside, acts as an activator of the HIF-1α pathway and shows potential in diabetic hind limb ischemia research [1].

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