norcantharidin

Norcantharidin is a synthetic small molecule and a demethylated analogue of cantharidin (the active ingredient in the traditional Chinese medicine *Mylabris*). It is water-soluble and has been approved by the Chinese FDA for the treatment of cancer, particularly hepatocellular carcinoma (HCC)[1][2]. Norcantharidin exerts anticancer effects through multiple mechanisms including induction of mitotic arrest, anti-proliferation, anti-metastasis activity, apoptosis induction, and cytotoxic autophagy or autophagic cell death[1]. Mechanistically it downregulates ISG15, MMP-9, uPA and Mcl-1; upregulates FAM46C and miR-214; modulates p21 Cip1/Waf1 and CDC25C phosphorylation; inhibits c-Met-mTOR and JAK/STAT3 signaling pathways; reverses methylation of RASSF1A gene; activates TRAIL-R2/DR5 signaling[1]. Norcantharidin also acts as a dual inhibitor for c-Met and EGFR in human colon cancers[5], induces apoptosis via TR3-dependent pathways in melanoma cells[6], suppresses breast cancer cell development by regulating miR axes affecting ERα transcriptional activity[3], and may help overcome resistance to targeted therapies in various cancers[3]. It generally exhibits lower toxicity than its parent compound cantharidin due to removal of methyl groups on its structure resulting in fewer side effects such as less myelosuppression or gastrointestinal toxicity[2].

Brand names

Haiyao

Other names

exo-7-oxabicylo[2.2.1]heptane-2,3-dicarboxylic anhydride7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic anhydridedemethylated cantharidin