COX-2 Inhibitor

HDAC6-IN-71 (Compound 24) is a HDAC6 inhibitor with IC₅₀ values for HDAC6 and HDAC1 of 13.68 and 443.12 nM respectively. HDAC6-IN-71 effectively inhibits the production of NO by mouse macrophages, with its IC₅₀ being 2.31 μM. HDAC6-IN-71 inhibits the HDAC6-NF-κB signaling pathway, reduces the levels of phosphorylated IκB-α and IKK-α/β, and suppresses the expression of downstream inflammatory proteins COX-2 and iNOS. HDAC6-IN-71 significantly alleviates ulcerative colitis in mice.

Triptolidenol, a traditional Chinese medicine, is an epoxy diterpene lactone that can be isolated from Tripterygium wilfordii. Triptolidenol has anti-inflammatory and anticancer activities. Triptolidenol significantly inhibits tumor cell proliferation and migration, arrests cell cycle arrest at S phase and induces apoptosis by activating the cytochrome c/caspase cascade signaling pathway. Triptolidenol disrupts NF-κB/COX-2 pathway by inhibiting IKKβ at ATP-binding sites. Triptolidenol can be used for chronic nephritis and kidney cancer like clear cell renal cell carcinoma (ccRCC) research.

COX-2/5-LOX-IN-7 (Hybrids 9) is a COX-2 (IC₅₀ = 3.3 μM)/5-LOX (IC₅₀ = 3.1 μM) inhibitor. COX-2/5-LOX-IN-7 can be used in research on diseases such as inflammation.

15-LOX-IN-2 (Compound 2a) is an orally active COX-2/15-LOX inhibitor and a partial agonist of PPARγ. 15-LOX-IN-2 has anti-inflammatory activity and inhibits the levels of 20-HETE, IL-1β and TNF-α in RAW 264.7 cells treated with LPS (HY-D1056). In addition, 15-LOX-IN-2 has significant glucose uptake capacity in the absence of insulin. 15-LOX-IN-2 can be used for the research of metabolic diseases.

COX-2-IN-61 is an orally active COX-2 inhibitor with an IC₅₀ of 22 µM, also inhibits COX-1 with an IC₅₀ of 43 µM. COX-2-IN-61 exhibits anti-inflammation effects in a Carrageenan (HY-125474) induced rat paw edema model, with promising safety profiles. COX-2-IN-61 can be used for the research of inflammation.

Dihydroflavokawin B is a selective COX-1 inhibitor with an IC₅₀ of 1.22 μM. Dihydroflavokawin B weakly inhibits COX-2 and 5-LOX. Dihydroflavokawin B inhibits promastigote forms of Leishmania panamensis and Leishmania braziliensis. Dihydroflavokawin B inhibits rabbit platelet aggregation induced by Arachidonic acid, platelet activating factor, and adenosine diphosphate. Dihydroflavokawin B exhibits in vitro anti-inflammatory activity. Dihydroflavokawin B can be used for the research of leishmaniasis.

COX-1/2-IN-11 is a dual inhibitor of COX-1 and COX-2, with an IC₅₀ of 345 nM against COX-1. COX-1/2-IN-11 can be used in the development of non-steroidal anti-inflammatory agents.

(±)-Methotrexate-d₃ ((±)-Amethopterin-d₃; (±)-CL14377-d₃; (±)-WR19039-d₃) is the deuterated-labeled (±)-Methotrexate (HY-121151). (±)-Methotrexate is the racemate of Methotrexate (HY-14519). Methotrexate is an orally active antifolate (Antifolate). Methotrexate inhibits dihydrofolate reductase (DHFR), blocks tetrahydrofolate production, suppresses purine/pyrimidine synthesis and transmethylation, and causes intracellular accumulation of AICAR. Methotrexate promotes extracellular adenosine release, regulates the cytokine network, and inhibits the alarmin function of HMGB1. Methotrexate induces apoptosis and cytotoxicity, upregulates the expression of iNOS and COX-2, suppresses hippocampal neurogenesis, and induces pulmonary fibrosis. Methotrexate is used in the research of various immune and inflammation-related diseases such as arthritis, psoriasis, systemic lupus erythematosus, as well as pulmonary fibrosis and breast cancer.

NF-κB/STAT3/iNOS-IN-1 is a NF-κB/STAT3/iNOS inhibitor. NF-κB/STAT3/iNOS-IN-1 reduces the expression of inflammatory mediators TNF-α, IL-1β, IL-6, IL-8 and COX-2. NF-κB/STAT3/iNOS-IN-1 upregulates the expression of epithelial barrier-related proteins E-cadherin, Occludin and Zonula occludens-1. NF-κB/STAT3/iNOS-IN-1 alleviates disease severity and histopathological damage in mouse colitis models. NF-κB/STAT3/iNOS-IN-1 can be used for the research of inflammatory bowel disease (colitis).

COX-2/PI3K-IN-1 (compound 5d) is a potent PI3K inhibitor with IC₅₀ value of 1.14 nM. COX-2/PI3K-IN-1 is a selective COX-2 inhibitor with K_i value of 3.24 nM. COX-2/PI3K-IN-1 has anti-inflammatory and anti-cancer properties.

AS1-6 is a selective COX-2 inhibitor with an IC₅₀ of 2.7 μM. AS1-6 has an IC₅₀ of 12.6 μM for COX-1. AS1-6 exerts significant anti-inflammatory and analgesic activities. AS1-6 can be used in research on non-steroidal anti-inflammatory agents.

Eltenac, a non-steroidal anti-inflammatory drug (NSAID), is a COX inhibitor. Eltenac shows IC50 of 0.03 μM for both COX-1 and COX-2 in isolated human whole blood.

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.

(±)-Methotrexate ((±)-Amethopterin; (±)-CL14377; (±)-WR19039) is the racemate of Methotrexate (HY-14519). Methotrexate is an orally active antifolate (Antifolate). Methotrexate inhibits dihydrofolate reductase (DHFR), blocks tetrahydrofolate production, suppresses purine/pyrimidine synthesis and transmethylation, and causes intracellular accumulation of AICAR. Methotrexate promotes extracellular adenosine release, regulates the cytokine network, and inhibits the alarmin function of HMGB1. Methotrexate induces apoptosis and cytotoxicity, upregulates the expression of iNOS and COX-2, suppresses hippocampal neurogenesis, and induces pulmonary fibrosis. Methotrexate is used in the research of various immune and inflammation-related diseases such as arthritis, psoriasis, systemic lupus erythematosus, as well as pulmonary fibrosis and breast cancer.

Kaempferol 3-O-(2G-glucosylrutinoside)-7-O-glucoside is an anti-inflammatory agent. Kaempferol 3-O-(2G-glucosylrutinoside)-7-O-glucoside exerts significant anti-inflammatory effects in LPS (HY-D1056)-induced RAW 264.7 macrophages by inhibiting the NF-κB, MAPK and Akt signaling pathways, thereby reducing the production of inflammatory mediators (NO, PGE2) and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6).

COX-2/15-LOX-IN-7 is a potent, selective and orally active dual inhibitor of COX-2 and 15-LOX with IC₅₀ values of 0.022 and 1.19 μM. COX-2/15-LOX-IN-7 also inhibits COX-1 with an IC₅₀ value of 28.081μM. COX-2/15-LOX-IN-7 has low cytotoxicity against human colorectal cancer HT-29 and HCT116 cell lines (IC₅₀ >100 μM for both). COX-2/15-LOX-IN-7 exhibits non-ulcerogenic performance. COX-2/15-LOX-IN-7 can be used for the research of cancer.

Melafolone is a potent dual COX-2/EGFR inhibitor with IC₅₀s of 13.2 μM (COX-2) and 17.4 μM (EGFR). Melafolone enhances the effect of anti-PD-1 through vascular normalization and PD-L1 downregulation via the PI3K/Akt pathway in Lewis lung carcinoma (LLC) and CMT167 models. Melafolone can be used for lung cancer research.

Tomoxiprole (MDL 035) is a new analgesic antiinflammatory agent. Tomoxiprole selectively inhibits cyclooxygenase-2 (IC₅₀ = 7 nM) .

COX-2-IN-54 (Compound 7y) is an orally active COX-2 inhibitor with an IC₅₀ of 4.15 μM. COX-2-IN-54 has a strong protective effect against DSS-induced ulcerative colitis and can significantly reduce tissue damage. COX-2-IN-54 has anti-inflammatory activity.

Cudraflavone B is a prenylated flavonoid with anti-inflammatory and anti-tumor properties. Cudraflavone B is also a dual inhibitor of COX-1 and COX-2. Cudraflavone B blocks the translocation of nuclear factor κB (NF-κB) from the cytoplasm to the nucleus in macrophages. Thus, Cudraflavone B inhibits tumor necrosis factor α (TNFα) gene expression and secretion. Cudraflavone B also triggers the mitochondrial apoptotic pathway, activates NF-κB, the MAPK p38, and ERK, and induced the expression of SIRT1. Thus Cudraflavone B inhibits the growth of human oral squamous cell carcinoma cells.