HIF 1α inhibitor 1

Indacaterol acetate is an ultra-long-acting beta-adrenoceptor agonist.

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 protein level without affecting its mRNA level.

HIF-1α inhibitor-1 is a HIF-1 alpha inhibitor.

HIF-1 inhibitor-5 (Compound 16e) is a potent HIF-1 inhibitor with an IC50 value of 2.38 μM, demonstrating significant anti-angiogenic potential [1].

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.

(±)-Evodiamine is an alkaloid isolated from Evodiae fructus and a topoisomerase I inhibitor. It also inhibits adipocyte differentiation and diabetes by downregulating IGF-1/HIF-1α and IL-6/STAT pathways. As an inhibitor of NF-κB activation, it suppresses invasion, promotes apoptosis, and inhibits TNF-induced Akt activation.

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

(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].

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.

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.

Multi-kinase-IN-8 is a multi-kinase inhibitor. It effectively inhibits COX-1 (IC50 = 12.6 μM), COX-2 (IC50 = 0.05 μM), and VEGFR-2 (IC50 = 0.12 nM). Additionally, it blocks tumor-associated carbonic anhydrases CA IX and CA XII with Ki values of 31.5 nM and 386.9 nM, respectively, and induces cell cycle arrest and apoptosis (apoptosis) by upregulating Caspase-9 and Bax, while downregulating Bcl-2. Multi-kinase-IN-8 also suppresses the expression of PGE2, p-VEGFR-2, MMP-9, and HIF-1α, and demonstrates growth inhibitory activity on breast, lung, and colorectal adenocarcinomas.

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

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

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.

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).

Dimethyl-bisphenol A (DMBPA) is a potent inhibitor of HIF-1α, promoting its degradation by dissociating Hsp90 from HIF-1α and thus decreasing the expression of Vegfa mRNA [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.

HIF-1α-IN-4 is an inhibitor of HIF-1α with IC50 of 24 nM in HEK293T cells which has potential antitumor effects. HIF-1α-IN-4 downregulates VEGF and PDK1 mRNA expressions under hypoxia [1].

HIF-1α-IN-5 is an inhibitor of HIF-1α with an IC 50 value of 24 nM in HEK293T cells that also inhibits the activity of MAO-A. HIF-1α-IN-5 downregulates the mRNA expressions of VEGF and PDK1 under hypoxia. HIF-1α-IN-5 has the potential to be used in the cancer research[1].

HIF-1/2α-IN-2 is a selective inhibitor targeting hypoxia-inducible factors 1α and 2α (HIF-1α and HIF-2α). It induces a state of cellular iron deficiency by inhibiting the activity of iron-sulfur cluster assembly protein 2 (ISCA2), thereby reducing HIF-2α synthesis and ultimately triggering ferroptosis. HIF-1/2α-IN-2 is widely used in research related to tumor biology, metabolic regulation, and ischemia.

HIF-1α-IN-3, also known as Compound (S)-3f, is a hypoxia-selective inhibitor of HIF-1α. It exhibits potent antiestrogenic activity [1].

HIF-1/2α-IN-1, an orally active compound, functions as an inhibitor of HIF-2α. Its inhibitory effect on HIF-2α activity is significant, with an IC 50 value of 0.92 μM. Furthermore, HIF-1/2α-IN-1 has the ability to decrease HIF-1α levels. This compound is particularly valuable for research on clear cell renal cell carcinoma (ccRCC) [1].

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), with potential applications in HIF-1α-related diseases, including peripheral vascular disease (PVD), heart failure, coronary artery disease (CAD), ischaemia, anaemia, colitis, and other inflammatory bowel diseases.