HIF-1α Inhibitor

PX-478 is a multifunctional HIF-1α inhibitor with properties including radiosensitization, autophagy activation, and lipid accumulation inhibition. PX-478 also blocks hypoxia-induced VEGF production and regulates β-cell phenotypes under hypoxic conditions. PX-478 induces cell cycle arrest and DNA damage, restores autophagic function, reduces foam cell formation, and maintains glucose homeostasis. PX-478 is widely used in research on related diseases such as human tumors (e.g., prostate cancer), type 2 diabetes, and atherosclerosis.

Sapanisertib (INK-128; MLN0128; TAK-228) is an orally active dual mTORC1/mTORC2 inhibitor. Sapanisertib directly and simultaneously inhibits mTORC1/2 activity through competitive binding with ATP, thereby comprehensively blocking downstream processes such as protein and lipid synthesis and cytoskeletal reorganization, consequently suppressing tumor cell proliferation and promoting apoptosis. Sapanisertib is applicable to research on melanoma, ovarian cancer, pulmonary fibrosis, and hematological malignancies.

Cryptochlorogenic acid (4-Caffeoylquinic acid) is a naturally occurring phenolic acid compound with oral effectiveness, anti-inflammatory, antioxidant and anti-cardiac hypertrophy effects. Alleviating LPS (HY-D1056) and ISO (HY-B0468) by regulating proinflammatory factor expression, inhibiting NF-κB activity, promoting Nrf2 nuclear transfer, and regulating PI3Kα/Akt/ mTOR / HIF-1α signaling pathway Induced physiological stress response.

IDF-11774 is a novel hypoxia-inducible factor α (HIFα)-1 inhibitor with an IC₅₀ of 3.65 μM.

Caulerpin is an orally active natural product with anti-tumor, anti-viral, anti-oxidant, anti-fungal, anti-bacteria and analgesic activities. Caulerpin acts as an inhibitor of mitochondrial ETC complex I and acetylcholinesterase. Caulerpin blocks hypoxia-induced activation of HIF-1α protein, inhibits VEGF secretion and tumor angiogenesis under hypoxic conditions, reduces the expression of NLRP3 and the production of pro-inflammatory cytokines, and suppresses the load of Mycobacterium tuberculosis. Caulerpin can be used in studies related to breast cancer, prostate cancer, tuberculosis and viral infections.

iGP-1 is a cell-permeable, selective mixed inhibitor of mitochondrial sn-glycerol-3-phosphate dehydrogenase (mGPDH), with IC₅₀s of 6.3 μM and 13.6 μM for rat mGPDH activity and H₂O₂ production, respectively. iGP-1 specifically blocks the mitochondrial component of the glycerophosphate shuttle without affecting cytosolic GPDH. iGP-1 not only inhibits cell proliferation and glutaminolysis, and enhances glycolysis, but also significantly alters key cellular physiological processes such as apoptosis, ROS production, HIF-1α stability and mitochondrial membrane potential. iGP-1 remains active in neutrophil cultures under both normoxic and hypoxic conditions, and serves as an ideal probe for glycerol-3-phosphate metabolic mechanisms. iGP-1 has been applied to studies on prostate cancer and related metabolic pathways.

Streptonigrin (Bruneomycin) is an orally active antibiotic and pan-PAD inhibitor, inhibiting PAD1, PAD2, PAD3 and PAD4 with IC₅₀ of 48.3 μM, 26.1 μM, 0.43 μM and 2.5 μM, respectively. Streptonigrin inhibits SENP1 (IC₅₀ of 0.518 μM) and reduces HIF1α. Streptonigrin increases p53 and Apoptosis. Streptonigrin shows antiviral activity against Rauscher murine leukemia virus. Streptonigrin has immunosuppressive effects. Streptonigrin has antitumor activity against osteosarcoma.

GW-405833 (L768242) is a potent, selective cannabinoid receptor 2 (CB₂) agonist. GW405833 has EC₅₀ and K_i values ​​of 0.65 nM and 3.92 nM for CB₂, and EC₅₀ and K_i values ​​of 16.1 μM and 4772 nM for CB₁. GW-405833 also exhibits non-competitive CB₁ antagonist, exerting its analgesic and and anti-inflammatory effect through a CB₁ receptor (rather than CB₂) dependent mechanism. GW-405833 can significantly inhibit the production of cAMP stimulated by Forskolin (HY-15371). GW405833 inhibits glycolysis by down-regulating HIF-1α, thereby alleviating acute liver failure (ALF).

Dendrophenol (Moscatilin) is a NF-κB inhibitor that inhibits inflammation. Dendrophenol exerts potent cytotoxic effect against tumor cells and induces cell cycle arrest and apoptosis. Dendrophenol has antitumor activity. In addition, Dendrophenol can inhibit vascular calcification by inhibiting the activation of WNT3/β-catenin.

GW405833 (L768242) hydrochloride is a potent, selective cannabinoid receptor 2 (CB₂) agonist. GW405833 has EC₅₀ and K_i values ​​of 0.65 nM and 3.92 nM for CB₂, and EC₅₀ and K_i values ​​of 16.1 μM and 4772 nM for CB₁. GW405833 hydrochloride also exhibits non-competitive CB₁ antagonist, exerting its analgesic effect through a CB₁ receptor (rather than CB₂) dependent mechanism. GW405833 hydrochloride can significantly inhibit the production of cAMP stimulated by Forskolin (HY-15371). GW405833 hydrochloride inhibits glycolysis by down-regulating HIF-1α, thereby alleviating acute liver failure (ALF).

Licoflavone A is an orally active PTP1B/VEGFR-2 inhibitor, with an IC₅₀ of 54.5 μM against PTP1B, an IC₅₀ of 14.36 μM and a K_d of 142.38 nM against human VEGFR-2. Licoflavone A blocks the PI3K/AKT and MEK/ERK signaling pathways. Licoflavone A induces G1 phase cell cycle arrest, apoptosis via the intrinsic mitochondrial pathway (apoptosis), and inhibits migration, invasion and epithelial-mesenchymal transition (EMT) of gastric cancer cells. Licoflavone A inhibits the proliferation of gastric cancer cells in vitro and in xenograft models. Licoflavone A reduces the expression levels of HIF-1α, GLUT1, LDHA, PKM2 and HK2 in hypoxic gastric cancer cells, decreases glucose uptake and suppresses glycolysis. Licoflavone A can be used in research related to gastric cancer, type 2 diabetes and obesity.

Iminostilbene is a chemical precursor of carbamazepine. Additionally, Iminostilbene is an orally active inhibitor of PKM2 (Pyruvate Kinase M2) and COX2 (Cyclooxygenase-2). Iminostilbene exerts its effects by inhibiting PKM2 and its interaction with HIF-1α and STAT3, reducing COX2 and iNOS expression, and decreasing LPS-induced release of IL-1β, IL-6, TNF-α, and MCP-1, thereby suppressing macrophage-mediated inflammatory responses and improving myocardial ischemia/reperfusion (MI/R) injury. Iminostilbene holds promise for research in inflammation regulation, cardiovascular diseases (such as MI/R injury), and macrophage-mediated immune-related diseases.

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.

Bendazol is an orally effective antihypertensive agent. Bendazol acts directly on vascular smooth muscle to dilate blood vessels and reduce peripheral resistance, thereby improving blood circulation. Bendazol significantly inhibits the development of myopia in rabbit models. Bendazol can regulate kidney function by increasing the activity of NO synthase in the rat model of nephrogenic hypertension. In addition, Bendazol has an effect on sexual behavior and spermatogenesis in male rats.

AG01 is a monoclonal antibody against progranulin (GP88). AG01 inhibits triple-negative breast cancer (TNBC) cell proliferation and migration, reduces the expression of phosphorylated protein kinases p-Src, p-AKT, and p-ERK, and reduces the expression of oncogenic proteins such as Axl, c-MET, HIF-1α, and VEGF. AG01 inhibits tumor growth and Ki67 expression in a TNBC xenograft mouse model. AG01 can be used in the research of TNBC and other cancers.

T7117 is a TRIM25-HIF-1α inhibitor. T7117 disrupts the interaction between TRIM25-HIF-1α. T7117 can be used for the research of glioblastoma.

MR-39 is a FPR2 agonist (EC₅₀ = 3.9 μM). MR-39 activates FPR2 to promote neuroinflammation resolution (downregulates IL-1β and TNF-α, modulates NF-κB), upregulates synaptic proteins (synaptic proteins) and improves dendritic spine morphology. MR-39 inhibits MAPK/ERK and AKT phosphorylation in glioblastoma, induces S-phase arrest, and suppresses migration, angiogenesis, and hypoxic adaptation. MR-39 reduces Aβ plaque burden via inhibiting MyD88/NF-κB and NLRP3 inflammasome. MR-39 can be used for research on autism spectrum disorder, Alzheimer's disease, and glioblastoma.

BCS12 is a CAIX inhibitor. BCS12 inhibits the viability of cancer cells under hypoxic conditions. BCS12 elevates ROS levels and suppresses the expression of HIF-1α and CA9. BCS12 downregulates Bcl-2, activates caspase-9, caspase-3, caspase-7 and Bax, and induces PARP cleavage and apoptosis. BCS12 reduces tumor burden, increases the number of apoptotic nuclei and restores tissue structure in rats bearing breast tumors. BCS12 can be used in research related to triple-negative breast cancer.

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.

L-Glutamine GMP is L-Glutamine (HY-N0390) produced by using GMP guidelines. GMP small molecules works appropriately as an auxiliary reagent for cell therapy manufacture. L-Glutamine is an orally active nutritional agent and cellular metabolism regulator. L-Glutamine is taken up in a Na⁺-dependent manner and targets multiple key molecules including glutaminase, mTORC1, NF-κB, STAT-3 and HIF-1α. L-Glutamine enhances glutaminolytic catabolism, drives the conversion of glutamate to α-ketoglutarate, thereby regulating gene expression, integrating metabolic signals, mediating glutamine flux and maintaining redox homeostasis. L-Glutamine also promotes cell proliferation, osteogenic differentiation and fracture healing, exerts neuroprotective and cardioprotective effects, and inhibits osteoarthritis. L-Glutamine can be applied to research related to osteoporosis, osteoarthritis, ischemic stroke and acute cantharidin-induced cardiotoxicity.