HIF

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

1. Cinnamaldehyde (Cinnamic Aldehyde) has antipyretic activity. 2. Cinnamaldehyde is a sedative agent. 3. Cinnamaldehyde inhibits invasive capabilities of MDA-MB-435S cells was correlated with down-regulating the expression of miR-27a. 4. Cinnamaldehyde induces the generation of reactive oxygen species and exerts vasodilator and anticancer effects. 5. Cinnamaldehyde appears to be a promising candidate as an adjuvant in combination therapy with 5-fluorouracil (5-FU) and oxaliplatin (OXA), two chemotherapeutic agents used in CRC treatment. The possible mechanisms of its action may involve the regulation of drugmetabolizing genes. 6. Cinnamaldehyde plays a certain role in inhibiting the occurrence and progression of melanoma and its action mechanism may be manifested by inhibiting expression of VEGF and HIF-αあるふぁ, thus blood vessel simulation and formation of new blood vessels of melanoma cells, and growth of tumors accordingly.

Acriflavine Hydrochloride (Acriflavine HCl) is a HIF-1αあるふぁ inhibitor. It acts by targeting HIF-1αあるふぁ-mediated pathways and decreasing the level of PGK1, VEGF, and HIF-1αあるふぁ in vitro and in vivo.

Dapagliflozin (BMS-512148) is a selective sodium-glucose co-transporter subtype 2 (SGLT2) inhibitor with antihyperglycemic activity.

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.

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.

Sodium Aescinate (Escin sodium salt) is extracted from Aesculus wilsonii.

Pantoprazole sodium (Pantecta) is the sodium salt form of a substituted benzimidazole with proton pump inhibitor activity. Pantoprazole sodium is a lipophilic, weak base that crosses the parietal cell membrane and enters the acidic parietal cell canaliculus where it becomes protonated, producing the active metabolite sulfenamide, which forms an irreversible covalent bond with two sites of the H+ K+-ATPase enzyme located on the gastric parietal cell, thereby inhibiting both basal and stimulated gastric acid production.

DMOG (Dimethyloxalylglycine), an antagonist of the αあるふぁ-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.

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あるふぁ which induces sVEGFR-1 production from tumor-associated macrophages and decreases tumor growth.

HIF-2αあるふぁ agonist 2 is an HIF-2αあるふぁ agonist with an EC50 value of 1.68 μみゅーM for HIF-2αあるふぁ. HIF-2αあるふぁ 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あるふぁ agonist 2 can be used in the study of oxygen metabolism and is closely related to the occurrence of cancer.

ML228 is a potent the Hypoxia Inducible Factor (HIF) pathway activator with EC50 of 1 μみゅーM. ML228 potently activates HIF in vitro as well as its downstream target VEGF.

ENMD-119 is a 2-methoxyestradiol analog with antiproliferative and antiangiogenic activity. It is suitable for inhibiting HIF-1αあるふぁ and STAT3 in human HCC cells.

M1002 is a hypoxia-inducible factor-2 (HIF-2) agonist that enhances the affinity of HIF-2alpha and ARNT for transcriptional activation. It alters the Tyr2 conformation of the HIF-2alpha PAS-B structural domain and acts synergistically with inhibitors of the prolyl hydroxylase structural domain (PHD).

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

Oligomycin is an antifungal antibiotic that is an inhibitor of H+-ATP synthetase. The Oligomycin blocks oxidative phosphorylation and the electron transport chain. Oligomycin inhibited HIF-1alpha expression in hypoxic tumor cells.

Deferoxamine（Desferrioxamine B） is an iron chelator (binds Fe(III) and many other metal cations) that inhibits neuronopathy, may be used to modify the reduction of iron accumulation and deposition in tissues, and may improve neurological dysfunction by inhibiting ferroptosis and neuroinflammation following traumatic brain injury.Desferrioxamin-B has antioxidant, antiproliferative, Deferoxamine has antioxidant, antiproliferative, and antitumor activities, and can induce HIF-1αあるふぁ production, apoptosis and autophagy in cancer cells.Desferrioxamin-B can be used in the treatment of acute iron toxicity and COVID-19 related diseases.

VH-298 is a potent inhibitor of VHL that stabilizes HIF-αあるふぁ and elicits a hypoxic response via a different mechanism, that is the blockade of the VHL:HIF-αあるふぁ protein-protein interaction downstream of HIF-αあるふぁ hydroxylation by PHD enzymes.

Lificiguat (YC-1) is an nitric oxide (NO)-independent activator of soluble guanylyl cyclase(sGC) and an inhibitor of Hypoxia-inducible factor-1alpha (HIF-1alpha).

Cucurbitacin B (Cuc B) has profound in vitro and in vivo antiproliferative effects against human pancreatic Y cells. It inhibited AKT signaling activation through up-regulation of PTEN. Cucurbitacin B is an effective inhibitor of HIF-1 and provide new perspectives into the mechanism of its anticancer activity. Cucurbitacin B inhibits proliferation and induces apoptosis via STAT3 pathway inhibition in A549 lung Y cells.

Ganetespib (STA-9090) is a synthetic small-molecule inhibitor of heat shock protein 90 (Hsp90), exhibiting potential antineoplastic activity.

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

IDF-11774 is a HIF-1 inhibitor.It reduces hif-1αあるふぁ HRE luciferase activity (IC50 = 3.65 μみゅーM).

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

2-Methoxyestradiol (2-ME2) is an orally bioavailable estradiol metabolite with potential antineoplastic activity. 2-Methoxyestradiol inhibits angiogenesis by reducing endothelial cell proliferation and inducing endothelial cell apoptosis. This agent also inhibits tumor cell growth by binding to tubulin, resulting in antimitotic activity, and by inducing caspase activation, resulting in cell cycle arrest in the G2 phase, DNA fragmentation, and apoptosis.

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

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

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

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

M1001 is a HIF-2αあるふぁ agonist.

Cephaeline was highly active against protected primary CLL cells (relative IC50's 35nM ) and acted by repressing HIF-1αあるふぁ± and disturbing intracellular redox homeostasis.

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

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

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

Acetylarenobufagin is a steroidal hypoxia-inducible factor-1 (HIF-1) modulator.

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あるふぁ transcriptional activity. However, It can not be suppressing HIF-1αあるふぁ mRNA expression, HIF-1αあるふぁ protein accumulation, or HIF-1αあるふぁ/HIF-1βべーた heterodimerization.

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

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

HIF-1 inhibitor-4 (HIF-1 inhibitor-4) is a HIF-1 inhibitor with IC50 of 560 nM. HIF-1 inhibitor-4 reduces the HIF-1αあるふぁ protein level without affecting its mRNA level.