HIF Inhibitor

Bavachinin is agonist of pan-peroxisome proliferator-activated receptor (PPAR), with the IC₅₀ value of 21.043 μM, 12.819 μM, and 0.622 μM to PPAR-α, RRAR-β/δ, and PPAR-γ, respectively. Bavachinin is an inhibitor of HIF-1α. Bavachinin exhibits antitumor activity against non-small cell lung cancer by targeting RRAR-γ. Bavachinin is a natural compound with anti-inflammatory and anti-angiogenic activities. Bavachinin has orally bioactivity..

TP0463518 is an orally active, competitive pan-inhibitor of hypoxia-inducible factor prolyl hydroxylases PHD1/2/3. TP0463518 competitively inhibits human PHD1 (IC₅₀=18 nM), PHD2 (K_i=5.3 nM), and PHD3 (IC₅₀=63 nM), and targets monkey PHD2 with an IC₅₀ of 22 nM. TP0463518 inhibits PHD-catalyzed hydroxylation to stabilize HIFα, thereby upregulating erythropoietin (EPO) expression and enhancing intestinal iron absorption (such as increased DMT-1 and dCYTb expression), improving anemia. TP0463518 is mainly used for the research of renal anemia and inflammatory anemia.

Izilendustat is a potent prolyl hydroxylase inhibitor. Izilendustat competitively inhibits HIFPH2 activity, blocks HIF-1α degradation, stabilizes HIF-1α and HIF-2α proteins, and upregulates downstream target gene expression. Izilendustat can reduce intestinal inflammation and damage, enhance the ability of phagocytes to clear pathogens, and improve ischemia-related pathological phenotypes. Izilendustat can be used for the research of inflammatory bowel disease, ischemic vascular disease and anemia.

RH01504 is a HIF2α inhibitor with a K_d value of 5.42 nM against human HIF2α. RH01504 inhibits the growth of renal cancer cells. RH01504 can be used in research related to renal cell carcinoma.

HIF-2α-IN-17 is a selective hypoxia-inducible factor 2α (HIF2α) inhibitor that binds to the PAS-B domain of HIF2α. HIF-2α-IN-17 disrupts the interaction between HIF2α and the molecular chaperone Hsp70, leading to proteasomal degradation of HIF2α. HIF-2α-IN-17 exhibits antitumor activity and induces apoptosis in cancer cells. HIF-2α-IN-17 is applicable for research on cancers such as clear cell renal cell carcinoma.

Cyclo CRLLIF is a dual inhibitor for hypoxia inducible factor (HIF) 1 and 2, which disrupts the interaction of both HIF1-α and HIF2-α with HIF1-β, with affinity for HIF1-α and HIF2-α PAS-B domains K_D of 14.5 and 10.2 μM, respectively.

PMX464 (AW 464) is a thiol-reactive quinol compound and an inhibitor of the thioredoxin-thioredoxin reductase (Trx/TrxR) system, with an IC₅₀ value of 6.5 μM against TrxR. PMX464 acts by irreversibly inhibiting the thioredoxin (Trx-1) system, blocking HIF-1α transcriptional activation and the NF-κB inflammatory pathway, inducing apoptosis, attenuating platelet function and inhibiting thrombosis, and specifically disrupting the trypanothione antioxidant metabolic network in parasites. PMX464 is used in research concerning malignant tumors (colorectal cancer, breast cancer, renal cancer, and leukemia), pulmonary inflammation, African sleeping sickness, and antithrombotic applications.

HIF-2α-IN-18 is a selective HIF-2α inhibitor with a human IC₅₀ of 8.1 nM. HIF-2α-IN-18 binds to the HIF-2α PAS-B domain, induces conformational perturbations at the HIF-2α/ARNT dimerization interface, destabilizes the HIF-2α/ARNT heterodimer, and blocks HIF-2α-mediated transcriptional activity. HIF-2α-IN-18 inhibits hypoxia-induced expression of HIF-2α target genes EPO and SERPINE1, without inhibiting HIF-1α target genes PGK1 and PDK1. HIF-2α-IN-18 can be used for the research of clear cell renal cell carcinoma, hepatocellular carcinoma^[1].

Cyclo CRVIIF is a dual inhibitor for hypoxia inducible factor (HIF) 1 and 2, which disrupts the interaction of both HIF1-α and HIF2-α with HIF1-β, with affinity for HIF1-α and HIF2-α PAS-B domains K_D of 65 and 123 μM, respectively.