HIF/HIF Prolyl-Hydroxylase Inhibitor

HIF-IN-3 is a HIF inhibitor. HIF-IN-3 blocks the dimerization of HIF-α with HIF-1β by binding to the PAS domain of HIF-α, and induces the degradation of HIF-1α and HIF-2α via the ubiquitin-proteasome pathway. HIF-IN-3 inhibits the expression of the endogenous HIF-1 target gene CA9 and the HIF-2 target gene EPO in cancer cells. HIF-IN-3 inhibits tumor growth in the BT-474 breast cancer model. HIF-IN-3 can be used for research on HIF-related tumors such as breast cancer, colorectal cancer, and head and neck squamous cell carcinoma.

Molidustat sodium is an orally active inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PH) with IC₅₀ values of 480 nM, 280 nM, and 450 nM for PHD1, PHD2, and PHD3, respectively. Molidustat sodium can elevate the levels of circulating erythropoietin (EPO) to near-normal physiological ranges. Molidustat sodium can be utilized in the research of renal anemia.

PHD-1-IN-2 is an orally active inhibitor of hypoxia-inducible factor prolyl hydroxylase domain 1 (PHD-1) with an IC₅₀ of 0.07 μM. PHD-1-IN-2 acts as a substrate of MDR1 in MDR1-MDCK cell monolayer assays. PHD-1-IN-2 can be used in the research of ischemia, inflammatory responses and neurodegenerative diseases, such as inflammatory bowel disease and ischemia-reperfusion injury.

Multi-kinase-IN-8 is a muti-kinase inhibitor. Multi-kinase-IN-8 inhibits COX-1 (IC₅₀ of 12.6 μM), COX-2 (IC₅₀ of 0.05 μM) and VEGFR-2 (IC₅₀ of 0.12 nM). Multi-kinase-IN-8 inhibits tumor-associated carbonic anhydrases (CA IX and CA XII with K_i of 31.5 nM and 386.9 nM, respectively). Multi-kinase-IN-8 triggers cell cycle arrest and apoptosis through upregulation of Caspase 9 and Bax along with downregulation of Bcl 2. Multi-kinase-IN-8 suppresses PGE2, p-VEGFR-2, MMP-9 and HIF-1α and exhibits growth-inhibitory activity against breast cancer, lung cancer, and colorectal adenocarcinoma.

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.

Minocycline-d₆ is deuterium labeled Minocycline (HY-17412A). Minocycline is an orally active, potent and BBB-penetrated semi-synthetic tetracycline antibiotic. Minocycline is a hypoxia-inducible factor (HIF)-1α inhibitor. Minocycline shows anti-cancer, anti-inflammatory, and glutamate antagonist effects. Minocycline reduces glutamate neurotransmission and shows neuroprotective properties and antidepressant effects. Minocycline inhibits bacterial protein synthesis through binding with the 30S subunit of the bacterial ribosome, resulting in a bacteriostatic effect.

HIF-2α-IN-16 (48) is a HIF-2α inhibitor, with an IC₅₀ of 0.091 μM.

HIF-2α-IN-5 is a potent HIF-2α inhibitor with an IC₅₀ of < 50 nM.

Aminoflavone is an anti-tumor agent. Aminoflavone inhibits the expression of ITGA6/SOX2 by activating the AhR-miR-125b-2-3p axis, thereby targeting breast cancer stem cells. Aminoflavone induces an increase in intracellular ROS, increases the level of oxidative DNA damage marker 8-oxodG and DNA-protein cross-links. Aminoflavone causes S-phase arrest, activates caspase-3/8/9 and induces apoptosis (apoptosis). Aminoflavone inhibits HIF-1α expression in a manner independent of AhR. Aminoflavone can be used for the study of breast cancer.

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.

HIF-1α-IN-7 (Compound D13) is a potent HIF-1α inhibitor. HIF-1α-IN-7 has neuroprotective activity. HIF-1α-IN-7 can be used in Alzheimer's disease research.

PHD2-IN-2 (Compound 12) is a PHD2 inhibitor, with an IC₅₀ of 34.3 nM. PHD2-IN-2 has high erythropoietin (EPO) inducing activity, with an EC₅₀ of 6.79 μM. PHD2-IN-2 can be used for the research of anemia, ischemia, and hypoxia.

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.