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.

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

HIF-1/2α-IN-2 is a potent inhibitor of HIF-1/2α, which effectively reduces the levels of HIF-1/2α. This compound elicits an iron starvation response by specifically targeting ISCA2, a key protein involved in Iron Sulfur Cluster Assembly 2. [1]

HIF-1α-IN-2 is a novel and highly potent HIF-1α inhibitor with anticancer and antitumor activity that inhibits the expression of HIF-1α and VEGF in a dose-dependent manner and inhibits cell migration.

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].

HIF-PHD-IN-2 (compound 25) is a highly effective PHD inhibitor, displaying IC50 values below 100 nM for PHD1, PHD2, and PHD3 [1].

HIF-2α-IN-7 is a hypoxia inducible factor 2α (HIF-2α) inhibitor. HIF-2α-IN-7 can inhibit HIF-2α with an EC 50 value of 6 nM. HIF-2α-IN-7 can be used for the research of various types of diseases including cancer , liver disease, inflammatory disease, pulmonary diseases and iron load disorders .

HIF-2α-IN-6 (117) is a HIF-2α inhibitor [1].

HIF-2α-IN-5 is a potent HIF-2α inhibitor with an IC 50 of < 50 nM [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].

HIF-2α-IN-1 is a potent HIF-2α inhibitor with IC50 values less than 500 nM.

HIF-2α-IN-3 is a HIF-2α alteration inhibitor with anti-tumor properties and may be used in the study of cardiovascular disease.

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.

M1002 is a hypoxia-inducible factor-2 (HIF-2) agonist that enhances the affinity of HIF-2alpha and ARNT for transcriptional activation.M1002 alters the Tyr2 conformation of the HIF-281alpha PAS-B structural domain and acts synergistically with inhibitors of the prolyl hydroxylase structural domain (PHD).

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

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, thus blood vessel simulation and formation of new blood vessels of melanoma cells, and growth of tumors accordingly.

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].

AT-533 is a potent inhibitor of Hsp90 and HSV. AT-533 blocks the HIF-1α/VEGF/VEGFR-2 signaling pathway, leading to suppress tumor growth and angiogenesis. AT-533 also inhibits the activation of the downstream pathways, including Erk1/2, FAK, Akt/mTOR/p70S6K,. AT-533 inhibits the cell migration, invasion, and the tube formation of human umbilical vein endothelial cells (HUVECs).

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.

Herboxidiene is a polyketide originally isolated from S. chromofuscus that has diverse biological activities.[1],[2,][3],[4],[5] It inhibits growth of HeLa S3, SK-MEL-2, PC3, A549, and EBC-1 cells with GI50 values ranging from 7.4 to 62 nM.3 Herboxidiene is cytostatic against human umbilical vein endothelial cells (HUVECs; (IC50 = 26 nM)) and inhibits VEGF-induced invasion and tube formation of serum-starved HUVECs in a concentration-dependent manner, indicating antiangiogenic activity.[4] Herboxidiene (0.05 μM) inhibits HIF-1α mRNA splicing and reduces HIF-1α protein levels in HepG2 cells grown under hypoxic conditions. It also inhibits splicing of p27Kip mRNA in HeLa cells in a concentration-dependent manner via interaction with the SAP155 subunit of the SF3b complex.[2] Herboxidiene (0.1 and 1 μM) increases LDL receptor promoter-driven transcription in a cell-based reporter assay.[5] It also exhibits herbicidal activity against wild buckwheat, morning glory, maize, hemp sesbania, and rapeseed when applied at 0.069 kg/hectare.[1]

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].

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.

22-(4′-py)-JA, a semisynthetic derivative of junamycin A isolated from the Thai blue sponge (Xestospongia sp.), exhibits antimetastatic properties by inhibiting the AKT/mTOR/p70S6K signaling pathway. It also impedes tumor cell invasion and angiogenesis in human umbilical vein endothelial cells (HUVEC), while suppressing the expression of metalloproteinases (MMP-2 and MMP-9), hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF). Its potent anticancer activity is particularly noted against non-small cell lung cancer (NSCLC) [1].

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

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.

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

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

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.

Zifcasiran, a hypoxia-inducible factor (HIF) synthesis reducer, exhibits antitumor activities and is utilized in advanced renal cell carcinoma research [1] [2].

KG-548 is an ARNT/TACC3 disruptor as well as a HIF-1α inhibitor. KG-548 directly interferes with the formation of the ARNT/TACC3 complex by competitively binding the ARNT PAS-B domain with TACC3. ARNT is the aryl hydrocarbon receptor nuclear translocator which is also known as HIF-β [1][2].

Langkamide is a HIF-2 inhibitor with EC₅₀ values of 14.0 uM.

CMC2.24 (TRB-N0224) is an orally active tricarbonylmethane agent that demonstrates effectiveness in inhibiting Ras activation and the downstream effector ERK1/2 pathway, thus effectively combating pancreatic tumor formation in mice. Additionally, CMC2.24 exerts potent inhibitory effects on zinc-dependent MMPs, with IC50s ranging from 2.0-69 μM. Furthermore, CMC2.24 aids in alleviating the progression of osteoarthritis by restoring cartilage homeostasis and inhibiting chondrocyte apoptosis through the NF-κB/HIF-2α axis[1][2][3].

PHD2-IN-1, a potent and orally active HIF prolyl hydroxylase 2 (PHD2) inhibitor, exhibits an IC50 of 22.53 nM and is applicable in anemia research [1].

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).

25(R,S)-Ruscogenin is a natual product.

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.

1-Palmitoyl-2-oleoyl-sn-glycerol, an endogenous metabolite, serves as a predominant diacylglycerol in the hormogonium-inducing factor (HIF)-1 [1].

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).

PX-12 (PX12) (1-methylpropyl 2-imidazolyl disulfide) is a small-molecule inhibitor of Trx-1 (thioredoxin-1), stimulates apoptosis, down-regulates HIF-1α and vascular endothelial growth factor (VEGF) and inhibits tumor growth in animal models. Since high levels of Trx-1 have been associated with colorectal, gastric and lung cancers, PX-12 is indicated as a potential cancer treatment in combination with chemotherapy for patients with advanced metastatic cancer. Initial trials correlated doses of Px-12 with increased patient survival.

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.

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

Izilendustat (hydrochloride) is a potent inhibitor of prolyl hydroxylase that stabilizes hypoxia-inducible factor-1 alpha (HIF-1α) and hypoxia-inducible factor-2 (HIF-2). Potential for HIF-1α-related diseases (including peripheral vascular disease (PVD), heart failure, coronary artery disease (CAD), ischaemia, anaemia, colitis and other inflammatory bowel diseases).

Roxadustat-13C-15N is 13C and 15N labeled Roxadustat.

Roxadustat-13C2-15N is 13C and 15N labeled Roxadustat.

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