Topo I Degrader

SN-38-A2 is a topoisomerase I (TOP1) degrader with an IC₅₀ of 6.2 nM in MIA PaCa-2 pancreatic cancer cells. SN-38-A2 mimics protein misfolding via an adamantane hydrophobic tag, hijacks the HSP90 chaperone system, and mediates TOP1 degradation through the ubiquitin-proteasome system. SN-38-A2 assembles with poly β-cyclodextrin to form pH-responsive nanoparticles, enabling site-specific release under the acidic conditions of the tumor microenvironment, and exhibits tumor growth inhibitory effects in MIA PaCa-2 pancreatic cancer and HCT116 colorectal cancer xenograft models. SN-38-A2 can be used in research related to pancreatic cancer, colorectal cancer, and breast cancer.

MN33-63 is a Bcl-2 inhibitor, caspase-3 activator and DNA crosslinker with broad-spectrum anticancer activity. MN33-63 improves the water solubility of SN-38 (HY-13704), inhibits tumor growth and proliferation in a dose-dependent manner, and causes no obvious toxicity. MN33-63 relieves the inhibition of the mitochondrial apoptotic pathway, initiates the apoptosis program, inhibits Topo I activity, and promotes its degradation via the ubiquitin-proteasome and autophagy-lysosome pathways. MN33-63 induces DNA crosslinking, G2/M cell cycle arrest, inhibition of cancer cell migration, and cancer cell apoptosis through the mitochondrial pathway. MN33-63 can be used in the research of colorectal cancer, cervical cancer, hepatocellular carcinoma, lung adenocarcinoma and gastric cancer.

MN33-47 is a multi-target anti-tumor compound with broad-spectrum anti-proliferative activity. MN33-47 relieves the inhibition of the mitochondrial apoptosis pathway by downregulating the anti-apoptotic protein Bcl-2, while activating caspase-3 and inhibiting Topoisomerase I activity, thereby promoting its degradation through the ubiquitin-proteasome and autophagy-lysosome pathways. MN33-47 can also induce DNA cross-linking and G2/M cell cycle arrest, inhibit cancer cell migration and activate the mitochondrial apoptosis pathway, thus exerting potent anti-tumor effects. MN33-47 can improve the water solubility of SN-38 (HY-13704), and exhibits dose-dependent tumor growth inhibition effects in CT26 tumor-bearing mouse models without obvious toxic and side effects. MN33-47 can be used in related studies on colorectal adenocarcinoma, cervical adenocarcinoma, hepatocellular carcinoma, alveolar basal epithelial adenocarcinoma, gastric cancer and colon cancer.