Demethylcantharidate disodium

Disodium demethylcantharidate (norcantharidate disodium, CAS No. 129-67-9) is a water-soluble sodium salt derivative of norcantharidin (NCTD). Its core therapeutic targets are protein serine/threonine phosphatases (PP1, PP2A, PP2B), and it can simultaneously regulate signaling pathways such as Wnt/β-catenin, EGFR, and c-Met, as well as apoptosis-related molecules (caspase-3/-9, Bax/Bcl-2) and matrix metalloproteinases (MMP-2/-9). It exhibits concentration-dependent cytotoxicity against various tumor cell lines in vitro, with IC₅₀ values (after 72-hour incubation) as follows: HCT-8 (21.65±3.14 μM), A549 (31.91±1.42 μM), HeLa (62.03±13.41 μM), HepG2 (15.42±3.59 μM), BGC-823 (36.33±2.76 μM), and MCF-7 (16.01±3.42 μM). The IC₅₀ can be further reduced after formulation modification with liposomes, nanoparticles, etc. Clinically, the effective therapeutic dose is mainly based on injectable formulations (10~30 mg per dose, calculated as norcantharidin), which can be administered via intravenous injection, hepatic artery cannulation, etc.; oral tablets (0.5 mg per tablet) are also available. The effective concentration in in vitro experiments is concentrated at the μg/mL level. Its biological activities include antitumor effects (inducing tumor cell apoptosis, inhibiting proliferation and metastasis) and immunomodulation (increasing white blood cell count, improving immune function). Moreover, its toxicity is lower than that of the parent drug NCTD, with only certain urinary toxicity and organ toxicity observed in high-dose or long-term use.

References:

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[2] Zhai BT, Sun J, Shi YJ, Zhang XF, Zou JB, Cheng JX, Fan Y, Guo DY, Tian H. Review targeted drug delivery systems for norcantharidin in cancer therapy. J Nanobiotechnology. 2022 Dec 3;20(1):509. doi: 10.1186/s12951-022-01703-3. PMID: 36463199; PMCID: PMC9719664.