HIF-IN-1

HIF-IN-1 is a potent inhibitor of hypoxia-inducible factor (HIF-1), which is associated with tumor and cancer cell proliferation and inhibits HIF-1α protein aggregation.

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

Verucopeptin is a pyranized cyclic peptide and an inhibitor of hypoxia-inducible factor 1 (HIF-1). It is an antibiotic effective against B16 melanoma, with anticancer activity, lowering the expression of HIF-1 target genes and HIF-1α protein levels. It can be used in cancer research.

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.

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).

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.

Caffeic Acid Phenethyl Ester (Phenylethyl Caffeate) (CAPE) inhibits the activation of nuclear transcription factor NF-kappa B and may suppress p70S6K and Akt-driven signaling pathways, with antineoplastic, cytoprotective and immunomodulating activities. CAPE is the phenethyl alcohol ester of caffeic acid and a bioactive component of honeybee hive propolis. In addition, CAPE inhibits PDGF-induced proliferation of vascular smooth muscle cells through the activation of p38 mitogen-activated protein kinase (MAPK) and hypoxia-inducible factor (HIF)-1alpha and subsequent induction of heme oxygenase-1 (HO-1).

PHD-1-IN-1 is a potent inhibitor of hypoxia-inducible factor prolylhydroxylase domain-1 (PHD-1) enzyme(IC50 = 0.034 μM).

HIF-2α-IN-1 is a potent inhibitor of HIF-2α, with IC50 values below 500 nM.

(S,R,S)-AHPC-C5-COOH (VH032-C5-COOH) is a synthesized conjugate for E3 ligase ligand-linker applications, combining the VH032 VHL-based ligand with a linker for PROTAC development. VH-032 is a selective and potent VHL/HIF-1α interaction inhibitor with a dissociation constant (Kd) of 185 nM, offering potential in anemia and ischemic diseases research[1].

Me-(S,R,S)-AHPC-PEG2-OTs is a conjugate of E3 ligase ligand and linker (E3 Ligase Ligand-Linker Conjugates) utilized in the synthesis of PROTAC HIF-1α degrader-1.

MDH1/2-IN-1 is an MDH1/2 inhibitor with IC50 values of 1.07 nM and 1.06 nM, respectively. It suppresses mitochondrial respiration and the HIF-1α pathway. MDH1/2-IN-1 exhibits significant antitumor potential and offers new avenues for developing drugs targeting cancer metabolism.

NF-κB/HIF-1α-IN-1 (compound 9c) effectively inhibits the NF-κB activation pathway and demonstrates selective antifibrotic activity. This compound exhibits no significant cytotoxicity in NCI tumor cell lines. In rat models, NF-κB/HIF-1α-IN-1 successfully ameliorates liver fibrosis, suppresses the expression levels of NF-κB and HIF-1α, and induces Nrf2.

Anti-inflammatory agent 79 (compound 17q) is an isoquinolinone derivative-based HIF-1 inhibitor (IC50: 0.55 μM), effectively blocking HIF-1 signaling and promoting the degradation of HIF-1α. It inhibits synovial invasion and migration, as well as angiogenesis. In mouse inflammation models, Anti-inflammatory agent 79 effectively reduces foot swelling and arthritis and lowers levels of inflammatory factors and angiogenesis in vivo.

HSP90-IN-30 (compound 3e) inhibits the activity of the HSP90 molecular chaperone. Under hypoxic conditions, HSP90-IN-30 suppresses HIF-1 transcriptional activity with an IC50 value of 2.16 μM.

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.

LXY6090 is a HIF-1 inhibitor. LXY6090 inhibited the activity of HIF-1 and downregulated the protein level of HIF-1α in breast cancer cells. LXY6090 showed in vivo anticancer efficacy by decreasing the HIF-1α expression in nude mice bearing MX-1 tumor xeno

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.

PRLX-93936 is a selective Ras pathway protein inhibitor that modulates RAS/JNK pathway-associated protein phosphorylation, induces caspase-dependent apoptosis and cell cycle arrest, and exhibits anticancer activity.

Gramicidin A is a peptide antibiotic isolated from B. brevis.Gramicidin A is a highly hydrophobic channel-forming ion carrier that forms monovalent cation-permeable channels in artificial membranes.Gramicidin A induces the degradation of hypoxia-inducible factor 1 alpha (HIF-1 alpha) and reduces the growth of a mouse xenograft model of human renal cell carcinoma. Gramicidin A has antibacterial, antimalarial and hemolytic activities.

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].

HIF-PHD-IN-1 is a pharmacological compound that acts as an orally active inhibitor of the hypoxia-inducible factor prolyl hydroxylase domain (HIF-PHD), displaying an IC50 of 54 nM for hHIF-PHD2. Its potential as a therapeutic agent for renal anemia is highly promising.

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.

Theaflavin 3,3'-digallate, a major polyphenol found in black tea, is an inducer of oxidative stress which has anti-inflammatory and cancer chemopreventive actions, it reduces tumor angiogenesis by downregulating HIF-1αand VEGF.