Desidustat is an inhibitor of HIF hydroxylase extracted from patent WO 2014102818 A1, compound example 2.
Naphthofluorescein inhibits the interaction between HIF-1 and Mint3.Naphthofluorescein suppresses Mint3-dependent HIF-1 activity and glycolysis in cancer cells and macrophages without cytotoxicity in vitro and adverse effect in vivo[1]. Naphthofluorescein is also a fluorescent pH-sensitive probe that can be used for functional Cerenkov imaging[2].
PHD-1-IN-1 is an orally active and potent HIF prolylhydroxylase domain-1 (PHD-1) inhibitor with an IC50 of 0.034 μM. PHD-1-IN-1 has a unique monodentate binding interaction with the active site Fe2+ ion and induces the formation of an “Arg367-out” pocket[1].
PT-2385 is a selective HIF-2α antagonist with a Ki of less than 50 nM.
PX-478 is an antitumor inhibitor of hypoxia-inducible factor-1α (HIF-1α).
AT-533 is a potent Hsp90 and HSV inhibitor. AT-533 suppresses tumor growth and angiogenesis by blocking the HIF-1α/VEGF/VEGFR-2 signaling pathway. AT-533 also inhibits the activation of the downstream pathways, including Akt/mTOR/p70S6K, Erk1/2 and FAK. AT-533 inhibits the tube formation, cell migration, and invasion of human umbilical vein endothelial cells (HUVECs)[1][2][3].
IDF-11774 is a novel hypoxia-inducible factor (HIF)-1 inhibitor with an IC50 of 3.65 μM. IDF-11774 has been approved as a clinical candidate for a phase I study.
(S,R,S)-AHPC-C5-COOH (VH032-C5-COOH) is a synthesized E3 ligase ligand-linker conjugate, contains the VH032 VHL-based ligand and a linker to form PROTACs. VH-032 is a selective and potent inhibitor of VHL/HIF-1α interaction with a Kd of 185 nM, has the potential for the study of anemia and ischemic diseases[1].
Glucosamine (hydrochloride) is a natural product.IC50 value:Target:In vitro: Glucosamine hydrochloride exhibited dose-dependent DPPH antioxidant activity [1]. Short-term (4 h) glucosamine hydrochloride treatment inhibited HIF-1α at the protein level, decreased phosphorylation of p70S6K and S6, translation-related proteins [2]. In the obstructed kidneys and TGF-β1-treated renal cells, glucosamine hydrochloride significantly decreased renal expression of α-smooth muscle actin, collagen I, and fibronectin [3]. In vivo:
Deoxyshikonin is isolated from Lithospermum erythrorhizon Sieb with antitumor activity. Deoxyshikonin increases the expression of VEGF-C and VEGF-A mRNA in HMVEC-dLy, promotes HIF-1α and HIF-1β subunit interaction and binds to specific DNA sequences targeted by HIF, indicates a prolymphangiogenesis as well as a proangiogenesis effect in vitro[1]. Deoxyshikonin shows significant synergic antimicrobial activity with tetracycline against S. pneumonia (MIC=17 μg/mL), also shows significantly inhibitory activities against MRSA[2].
MK-8617 is an orally active pan-inhibitor of hypoxia-inducible factor prolyl hydroxylase 1-3 (HIF PHD1-3) with an IC50 of 1 nM for PHD2.
Verucopeptin is a potent HIF-1 (IC50=0.22 μM) inhibitor and decreases the expression of HIF-1 target genes and HIF-1α protein levels[1][2]. Verucopeptin strongly inhibits v-ATPase activity by directly targeting the v-ATPase ATP6V1G subunit but not ATP1V1B2 or ATP6V1D. Verucopeptin exhibits antitumor activity against multidrug resistance (MDR) cancers and can be used for cancer research[3].
TC-S 7009 is a potent and selective HIF-2α inhibitor with a Kd of 81 nM. TC-S 7009 is more selective for HIF-2α than HIF-1α (Kd ≫ 5 μM). TC-S 7009 disrupts HIF-2α heterodimerization, decreases DNA-binding activity, and reduces HIF-2α target gene expression[1][2].
Glucosamine-2-13C hydrochloride is the 13C 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, is used as
KG-548 is an ARNT/TACC3 disruptor and a HIF-1α inhibitor. KG-548 directly interferes with ARNT/TACC3 complex formation by competing with TACC3 for binding to the ARNT PAS-B domain. ARNT is the aryl hydrocarbon receptor nuclear translocator, also known as HIF-β[1][2].
Daprodustat (GSK1278863) is an orally active hypoxia-inducible factor prolyl hydroxylase inhibitor being developed for the treatment of anemia associated with chronic kidney disease.
Acriflavine hydrochloride (Acriflavinium chloride hydrochloride) is a fluorescent acridine dye that can be used to label nucleic acid[1][2]. Acriflavine hydrochloride is an antiseptic. Acriflavine hydrochloride is a potent HIF-1 inhibitor, with antitumor activity. Acriflavine hydrochloride has antimicrobial and antiviral activities[3][4][5]. Acriflavine hydrochloride is a potent papain-like protease (PLpro) inhibitor, which inhibits SARS-CoV-2[6]
Dencichin is a non-protein amino acid originally extracted from Panax notoginseng, and can inhibit HIF-prolyl hydroxylase-2 (PHD-2) activity.
Izilendustat is a potent inhibitor of prolyl hydroxylase which can stabilize hypoxia inducible factor- 1 alpha (HIF- lα) and hypoxia inducible factor-2 (HIF-2). Izilendustat has the potential for researching diseases that relate to the body’s inmmune response like colitis and other inflammatory bowel diseases (extracted from patent WO2011057115A1 and WO2011057121A1)[1][1].
TAT-cyclo-CLLFVY is a selective HIF-1 dimerization inhibitor. TAT-cyclo-CLLFVY blocks protein-protein interaction of recombinant HIF-1α, but not HIF-2α, with HIF-1β (IC50=1.3 μM). TAT-cyclo-CLLFVY inhibits hypoxia-induced HIF-1 activity, and decreases VEGF and CAIX expression in osteosarcoma and breast cancer cells in vitro. TAT-cyclo-CLLFVY also reduces tubularization of hypoxic HUVECs.
OHM1 is a potent HIF1α mimic that binds to CH1 domain of p300/CBP with Kd of 500 nM, reduces the level of HIF1α transcriptional activity under hypoxia to that observed under normoxia at 20 uM in A549 cells; reduces the median tumor volume in murine tumor xenografts, and does not cause measurable changes in animal body weight or other signs of toxicity in tumor-bearing animals.
Zifcasiran is a hypoxia-inducible factor (HIF) synthesis reducer. Zifcasiran shows antitumor activities and can be used in advanced renal cell carcinoma research[1][2].
Hydralazine Hydrochloride is a direct-acting vasodilator that is used as an antihypertensive agent.Target: OthersHydralazine (apresoline) is a direct-acting smooth muscle relaxant used to treat hypertension by acting as a vasodilator primarily in arteries and arterioles. By relaxing vascular smooth muscle, vasodilators act to decrease peripheral resistance, thereby lowering blood pressure and decreasing afterload. However, this only has a short term effect on blood pressure, as the system will reset to the previous, high blood pressure necessary to maintain pressure in the kidney necessary for natriuresis. The long term effect of antihypertensive drugs comes from their effects on the pressure natriuresis curve. It belongs to the hydrazinophthalazine class of drugs [1]. Hydralazine may reduce blood pressure when compared to placebo in patients with primary hypertension, however this data is based on before and after studies, not RCTs. Furthermore, its effect on clinical outcomes remains uncertain [2].
Zifcasiran sodium is a hypoxia-inducible factor (HIF) synthesis reducer. Zifcasiran sodium shows antitumor activities and can be used in advanced renal cell carcinoma research[1][2].
Tilorone dihydrochloride is the first recognized synthetic, small molecular weight compound that is an orally active interferon inducer, used as an antiviral drug.
VCE-004.8, a semi-synthetic multitarget cannabinoquinoid, is a specific PPARγ and CB2 receptor dual agonist with potent anti-inflammatory activity[1]. VCE-004.8 inhibits prolyl-hydroxylases (PHDs) and activates the HIF pathway. VCE-004.8 attenuates adipogenesis and prevents diet-induced obesity[2].
Paeoniflorin is a herbal constituent extracted from the root of Paeonia albiflora Pall.Target: OthersPaeoniflorin (PF) is the principal bioactive component of Radix Paeo- niae alba, which is widely used in Traditional Chinese Medicine for the treatment of neurodegenerative disorders such as Parkinson's disease(PD) [1]. Paeoniflorin, a compound found in white peony that inhibited the production of testosterone and promoted the activity of aromatase, which converts testosterone into estrogen [2]. Treatment of cells with paeoniflorin but not glycyrrhizin resulted in enhanced phosphorylation and acquisition of the deoxyribonucleic acid-binding ability of heat shock transcription factor 1 (HSF1), as well as the formation of characteristic HSF1 granules in the nucleus, suggesting that the induction of HSPs by paeoniflorin is mediated by the activation of HSF1. Also, thermotolerance was induced by treatment with paeoniflorin but not glycyrrhizin. Paeoniflorin had no toxic effect at concentrations as high as 80 microg/ mL (166.4 microM). To our knowledge, this is the first report on the induction of HSPs by herbal medicines [3].
PHD-IN-2 (Compound 91) is a PHD antagonist (IC50: < 5 nM). PHD-IN-2 induces erythropoietin synthesis in HEP3B cells (EC50: <2.5 μM). PHD-IN-2 can be used for research of cardiovascular disorders, metabolic disorders, hematological disorders, pulmonary disorders, kidney disorders, liver disorders, wound healing disorders, and cancer[1].
PT2399 is an inhibitor of HIF2α[1].
SYP-5 is a novel HIF-1 inhibitor, suppresses tumor cells invasion and angiogenesis.