Berberrubine chloride

Berberrubine chloride (CAS No. 15401-69-1) is the hydrochloride salt form of Berberrubine (CAS No. 17388-19-1). Berberrubine is a natural isoquinoline alkaloid derived from traditional Chinese medicines such as Coptis chinensis (berberine, Berberine (CAS No. 2086-83-1) major metabolite), with core biological functions including antibacterial, anti-inflammatory, hypoglycemic, anti-hyperuricemia, anti-thrombosis, and inhibition of tumor proliferation such as colorectal cancer and non-small cell lung cancer (NSCLC); it can also activate glutathione S-transferase Mu2 (GSTM2) to exert tumor-suppressive effects; its targets and mechanisms are diverse: inhibition of IMP dehydrogenase 2 (IMPDH2, competitive binding, with selectivity for IMPDH2 more than 15-fold higher than IMPDH1), thioredoxin reductase (TrxR, specifically targeting the Sec498 residue), vitamin K epoxide reductase (VKOR) and γ-glutamyl carboxylase (GGCX), activation of GSTM2 (via activation by the SP1 transcription factor and DNA demethylation), inhibition of NF-κB nuclear translocation, the JAK2/STAT3 signaling pathway, and urate transporters URAT1/GLUT9, upregulation of urate excretion transporters OAT1/3/ABCG2, and it can also inhibit topoisomerase II-mediated DNA cleavage; key activity data: IMPDH2 inhibition IC₅₀ 2.37 μM, TrxR inhibition IC₅₀ 5.0 μM, MIC values against fungi such as Candida albicans of 1-16 μg/mL (the 13-(4 - isopropylbenzyl) derivative is the most potent); commonly used animal models include the AOM/DSS-induced colorectal cancer model, the PO/HX-induced hyperuricemia model, the carrageenan-induced thrombosis model, the DSS-induced ulcerative colitis model, and the NSCLC xenograft model.

Common applications and concentrations: in cell culture, SW620/LS174T colorectal cancer cells 10-80 μM, A549 NSCLC cells 20-50 μM, ARPE-19 retinal pigment epithelial cells 0.2-25 μM, BFTC 905 bladder cancer cells 50 μM; in animal studies, oral dosing in the colorectal cancer model 25-50 mg/kg/d, oral dosing in the hyperuricemia model 6.25-25 mg/kg/d, oral dosing in the thrombosis model 50-100 mg/kg/d, oral dosing in the colitis model 100-200 mg/kg/d; no direct clinical application concentrations; effective therapeutic concentrations: at the cellular level, 10-80 μM can inhibit tumor cell proliferation, and 20 μM combined with cisplatin can enhance NSCLC chemosensitivity; at the animal level, 25-50 mg/kg/d can significantly inhibit colorectal tumor growth, 25 mg/kg/d can reduce serum uric acid levels in hyperuricemic mice by more than 75%, and 100 mg/kg orally can inhibit thrombosis without increasing bleeding risk.

References:

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[7] Wang C, Yuan Z, Xie J, Lei Y, Li Y, Huang J, Kong W, Jiang J. Integrated metabolomics and molecular docking reveal berberrubine inhibits thrombosis by regulating the vitamin K catalytic cycle in mice. Eur J Pharmacol. 2023 Jan 5;938:175436. doi: 10.1016/j.ejphar.2022.175436. Epub 2022 Dec 5. PMID: 36481237.

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[9] Rao J, Wang T, Yu L, Wang K, Qiu F. Inactivation of CYP2D6 by Berberrubine and the Chemical Mechanism. Biochemistry. 2024 Dec 3;63(23):3078-3089. doi: 10.1021/acs.biochem.4c00450. Epub 2024 Nov 21. PMID: 39569501.

[10] Chu Y, Nie Q, Zhou X, Yang J, Fang J, Zhang J. Berberrubine as a novel TrxR inhibitor enhances cisplatin sensitivity in the treatment of non-small cell lung cancer. Bioorg Chem. 2025 May;158:108329. doi: 10.1016/j.bioorg.2025.108329. Epub 2025 Mar 3. PMID: 40056602.