GN44028 is a hypoxia inducible factor (HIF)-1 inhibitor, with an IC50 of 14 nM. GN44028 inhibits hypoxia-induced HIF-1α transcriptional activity without suppressing HIF-1α mRNA expression, HIF-1α protein accumulation, or HIF-1α/HIF-1β heterodimerization[1].
Chlorogenic acid is a major phenolic compound in coffee and tea. It plays several important and therapeutic roles such as antioxidant activity, antibacterial, hepatoprotective, cardioprotective, anti-inflammatory, antipyretic, neuroprotective, anti-obesity, antiviral, anti-microbial, anti-hypertension.
JNJ-42041935 is a potent, competitive and selective inhibitor of prolyl hydroxylase PHD; inhibits PHD1, PHD2, and PHD3 with pKi values of 7.91±0.04, 7.29 ±0.05, and 7.65±0.09, respectively.
HIF-2α-IN-6 (117) is a HIF-2α inhibitor[1].
PT2977 is an orally active and selective HIF-2α inhibitor with an IC50 of 9 nM. PT2977, as a second-generation HIF-2α inhibitor, increases potency and improves pharmacokinetic profile. PT2977 is a potential treatment for Clear cell renal cell carcinoma (ccRCC) and von Hippel–Lindau (VHL) disease[1].
IOX4 is a selective HIF prolyl-hydroxylase 2 (PHD2) inhibitor with an IC50 value of 1.6 nM, induces HIFα in cells and in wildtype mice with marked induction in the brain tissue. IOX4 competes with and displaces 2-oxoglutarate (2OG) at the active site of PHD2[1].
A novel potent, orally active HIF prolyl hydroxylase (PHD) inhibitor with IC50 of 0.22 uM for PHD2; increases EPO release from Hep3B cells with EC50 of 5.7 uM, increases hemoglobin levels in rats. Anemia Phase 2 Clinical
HIF-2α-IN-2 is a hypoxia-inducible factors (HIF-2α) inhibitor extracted from patent WO2015035223A1, Compound 232, has an IC50 of 16 nM in scintillation proximity assay (SPA)[1].
DMOG (Dimethyloxallyl Glycine) is a cell-permeable and competitive inhibitor of HIF-1α prolyl hydroxylase (HIF-PH).
ML228(CID-46742353) is an activator of the Hypoxia Inducible Factor (HIF) pathway; potently activate HIF in vitro as well as its downstream target VEGF.IC50 value: 1 uM (EC50) [1]Target: HIF activatorML228 represents a novel chemotype available to the research community for the study of HIF activation and its therapeutic potential. Not only is the compound substantially different in structure from known HIF activators, ML228 lacks the acidic functional group almost universally present in PHD inhibitors, which may be important for certain disease applications.
GEM-5 is a gemcitabine-based conjugate containing a HIF-1α inhibitor (YC-1) (IC50=30 nM). GEM-5 can significantly down-regulate the expression of HIF-1α and up-regulate the expression of tumor suppressor p53. GEM-5 induces the apoptosis of A2780 cells and inhibits tumor growth[1].
HIF-PHD-IN-2 (compound 25) is a potent PHD inhibitor with IC50s of <100 nM for PHD1, PHD2 and PHD3, respectively[1].
PHD2-IN-1 is a potent and orally active inhibitor of HIF prolyl hydroxylase 2 (PHD2) with an IC50 of 22.53 nM. PHD2-IN-1 can be used for anemia research[1].
HIF-2α-IN-7 is a hypoxia inducible factor 2α (HIF-2α) inhibitor. HIF-2α-IN-7 can inhibit HIF-2α with an EC50 value of 6nM. 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[1].
Glucosamine-13C,15N hydrochloride is the 13C and 15N labeled Glucosamine hydrochloride. Glucosamine hydrochloride (D-Glucosamine hydrochloride) is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids, i
CL67 is a potent hypoxia-inducible factor (HIF) pathway inhibitor. CL67 interferes G-quadruplex structures within promoter sequences. CL67 can be used in research of renal cancer[1].
Dimethyl-bisphenol A (DMBPA) is a potent HIF-1α inhibitor. Dimethyl-bisphenol A can decrease Vegfa mRNA expression[1].
HIF-2α-IN-9 (compound 35r) is an inhibitor ofHIF-2α. HIF-2α-IN-9 inhibits VEGF-A (IC50=305 nM), and regulates growth-promoting genes in tumor cells, reactivates macrophage-mediated tumor immunity[1].
AFP464, is an active HIF-1α inhibitor with an IC50 of 0.25 μM, also is a potent aryl hydrocarbon receptor (AhR) activator.
HIF-2α-IN-8 is a potent and orally active HIF2α inhibitor with IC50 values of 9, 37, 246 nM for HIF2α SPA, HIF2α iScript, HIF2α HRE RGA, respectively. HIF-2α-IN-8 shows antitumor activity[1].
HIF-2α-IN-3, an allosteric inhibitor of hypoxia inducible factor-2α (HIF-2α), exhibits an IC50 of 0.4 µM and a KD of 1.1 µM. Anticancer agent[1].
Acetyl-11-Keto-β-Boswellic Acid (AKBA) is an active triterpenoid compound from the extract of Boswellia serrate; a novel Nrf2 activator.IC50 value:Target: Nrf2 activatorin vitro: AKBA significantly reduced infarct volumes and apoptotic cells, and also increased neurologic scores by elevating the Nrf2 and HO-1 expression in brain tissues in middle cerebral artery occlusion (MCAO) rats at 48 hours post reperfusion. In primary cultured neurons, AKBA increased the Nrf2 and HO-1 expression, which provided protection against OGD-induced oxidative insult. Additionally, AKBA treatment increased Nrf2 binding activity to antioxidant-response elements (ARE) [1]. AKBA significantly inhibited human colon adenocarcinoma growth, showing arrest of the cell cycle in G1-phase and induction of apoptosis[3]. AKBA triggered significant lipolysis in 3T3-L1 adipocytes as shown by reduced neutral lipids in cytosol and increased free fatty acids in culture medium. Increased lipolysis by AKBA was accompanied by up-regulation of lipolytic enzymes, adipocyte triglyceride lipase (ATGL) and hormone sensitive lipase (HSL), and a decreased expression of lipid droplet stability regulator perilipin. In addition, AKBA treatment reduced phenotypic markers of mature adipocyte aP2, adiponectin and glut-4 in mature adipocytes [5].in vivo: AKBA significantly prevented the formation of intestinal adenomatous polyps without toxicity to mice. AKBA's activity both in the prevention of small intestinal and colonic polyps was more potently than aspirin. Histopathologic examination revealed that AKBA's effect, that is the reduction of polyp size and degree of dysplasia, was more prominent in larger sized polyps, especially those originating in colon [2]. AKBA administration in mice effectively delayed the growth of HT-29 xenografts without signs of toxicity. The activity of AKBA was more potent than that of aspirin [3]. AKBA exhibited anti-cancer activity in vitro and in vivo. With oral application in mice, AKBA significantly inhibited SGC-7901 and MKN-45 xenografts without toxicity [4].
7-Hydroxyneolamellarin A is a natural product that could be derived from sponge Dendrilla nigra. 7-Hydroxyneolamellarin A is a potent hypoxia-inducible factor-1α (HIF-1α) inhibitor. 7-Hydroxyneolamellarin A attenuates the accumulation of hypoxia-inducible factor-1α (HIF-1α) protein and inhibits vascular epidermal growth factor (VEGF) transcriptional activity. 7-Hydroxyneolamellarin A can be used in research of cancer[1].
Izilendustat (hydrochloride) is a potent inhibitor of prolyl hydroxylase which stabilizes hypoxia inducible factor- 1 alpha (HIF- lα), as well as hypoxia inducible factor-2 (HIF-2). Izilendustat (hydrochloride) has the potential for the research of HIF- lα related diseases including Peripheral Vascular Disease (PVD), Coronary Artery Disease (CAD), heart failure, ischemia, anemia, colitis, and other inflammatory bowel diseases (extracted from patent WO2011057115A1/WO2011057112A1/WO2011057121A1)[1][2][3].
Oltipraz has an inhibitory effect on HIF-1α activation by insulin in a time-dependent manner, completely abrogating HIF-1α induction at ≥10 μM concentrations, the IC50 of Oltipraz for HIF-1α inhibition is 10 μM.IC50 value: 10 μMTarget: HIF-1αin vitro: Oltipraz inhibits HIF-1α activity and HIF-1α-dependent tumor growth, which may result from a decrease in HIF-1α stability through S6K1 inhibition in combination with an H2O2-scavenging effect. Oltipraz treatment also inhibits HIF-1α activation stimulated by either hypoxia or CoCl2. Oltipraz is a cancer chemopreventive agent and has an inhibitory effect on angiogenesis and tumor growth. [1] Oltipraz is also a competitive inhibitor of this cytochrome P450, with an apparent Ki of 10 μM. [2]in vivo: In wild-type mice, hepatic levels of mRNA for all of the genes analyzed were significantly increased after Oltipraz treatment, with the highest increase (treated/control) for NQO1 mRNA levels (7.6-fold). The Northern blot analyses demonstrated that the observed increases in GST and NQO1 activities by Oltipraz in wild-type mice were preceded by significant elevations in RNA expression. Interestingly, mRNA levels of Nrf2 itself were increased more than 3-fold by Oltipraz treatment. [2]
KC7F2 is a potent HIF-1 pathway inhibitor and that its potential as a cancer therapy agent warrants further study.Target：HIFin vitro: KC7F2 is the second HIF-1α inhibitor. KC7F2 is shown to inhibit the proliferation of cancer cells, an effect that is increased in hypoxia, while non-tumor cells are less sensitive. KC7F2 decreases HIF-1α levels by downregulating HIF-1α protein synthesis. [2] KC7F2 markedly inhibits HIF-mediated transcription in cells derived from different tumor types, including glioma, breast and prostate cancers and exhibited enhanced cytotoxicity under hypoxia. KC7F2 prevents the activation of HIF-target genes such as Carbonic Anhydrase IX, Matrix Metalloproteinase 2 (MMP2), Endothelin 1 and Enolase 1. KC7F2 works through the down-regulation of HIF-1α protein synthesis, an effect accompanied by the suppression of the phosphorylation of eukaryotic translation initiation factor 4E binding protein 1 (4EBP1) and p70 S6 kinase (S6K), key regulators of HIF-1α protein synthesis.[1]
(S,R,S)-AHPC-C2-amide-benzofuranylmethyl-pyridine is a dual target PROTAC that can not only target to the ubiquitination and degradation of Smad3 but also improve the HIF-α protein level. (S,R,S)-AHPC-C2-amide-benzofuranylmethyl-pyridine has a multi-path anti-fibrosis function and a renal protection function for research of renal anemia[1].
ZINC13466751 is a potent inhibitor of HIF-1α/von Hippel-Lindau interaction with an IC50 of 2.0 µM[1].
Oroxylin A is a natural active flavonoid with strong anticancer effects.IC50 value:Target:In vitro: Oroxylin A suppressed the MDM2-mediated degradation of p53 via downregulating MDM2 transcription in wt-p53 cancer cells [1]. Oroxylin A remarkably reduced the generation of lactate and glucose uptake under hypoxia in HepG2 cells, inhibited HIF-1α expression and its stability [2]. Oroxylin A promotes superoxide dismutase (SOD2) gene expression through SIRT3-regulated DNA-binding activity of FOXO3a and increases the activity of SOD2 by promoting SIRT3-mediated deacetylation [3]. In vivo: Oroxylin A inhibited the tumor growth of nude mice-inoculated MCF-7 or HCT116 cells. The expression of MDM2 protein in tumor tissue was downregulated by oroxylin A as well [1].
M1001 is a weak agonist of HIF-2α, directly binds to the HIF-2α PAS-B domain, with a Kd of 667 nM. M1001 enhances the stabilities of HIF-2α-ARNT complex[1].