Product name: Rankinidine
Synonym name: Demethoxyhumantenirine; N-Demethylhumantenine
Catalogue No.: BP4260
Cas No.: 106466-66-4
Formula: C₂₀H₂₄N₂O₃
Mol Weight: 340.423
Botanical Source: Gelsemium elegans
Type of Compound: Alkaloids

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle

Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.

The product could be supplied from milligrams to grams
Inquire for bulk scale.

For Reference Standard and R&D, Not for Human Use Directly.

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Natural products, as an important source of drug discovery, play an irreplaceable role in the field of anti-tumor drug development. In recent years, research on active ingredients based on traditional medicinal plants has deepened, and many natural compounds with potential clinical applications have been discovered and developed. 4-Demethyl Rankinidine is a hydroxyindole alkaloid isolated from the methanol extract of Gelsemium rankinii, a plant of the Yellow Vines genus. It has attracted attention for its unique chemical structure and multi-target pharmacological activity. As a malignant tumor with high incidence and mortality rates worldwide, liver cancer urgently needs new, effective, and low-toxicity treatments. Previous studies have shown that 4-demethyl Turpentine B has significant regulatory effects in liver cancer-related signaling pathways, especially showing strong inhibitory activity against key targets such as BCL2, STAT3, and TOP1, demonstrating good antitumor potential. This article will systematically review the chemical structure, origin, pharmacological activity, mechanism of action, and druggability evaluation of 4-desmethyl uncanterine B, exploring its prospects in liver cancer treatment.

Chemical structure and physicochemical properties

4-Demethyl Humantine B belongs to the hydroxyindole alkaloid class, with a molecular formula of C20H26N2O3 and a molecular weight of 340.4230. Its structural features include typical indole ring systems and hydroxyl substituents, and demethylation modification distinguishes it from Humantridge B in molecular conformation and polarity. The LogP value was 1.9978, indicating that the compound has moderate lipid solubility, which is beneficial for cell membrane penetration and distribution in vivo. The topological pole surface area (TPSA) is 50.8 Ų, making it a moderately polar molecule with excellent water solubility (2.3521 mg/mL) and lipid solubility balanced, which helps improve its bioavailability. The blood-brain barrier penetration ability is relatively high, suggesting it may also have potential effects on central nervous system diseases. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames-induced mutagenic test value was 1.2, indicating a relatively low genotoxicity risk. Overall, 4-desmethyl unsurmantine B possesses good physicochemical properties and a safety foundation, laying a solid foundation for further drug development.

Plant Origins and Extraction Methods

4-Demethyl Tempantine B mainly comes from the Yellow Vines genus Gelsemium rankinii, which is widely distributed in parts of Asia and the Americas and has long been used in folk traditional medicine, possessing multiple pharmacological effects including analgesic, anti-inflammatory, and anti-tumor effects. After extracting the whole plant or rhizome of Gelsemium rankinii with methanol (MeOH), high-purity 4-demethylated Rhizoethine B can be obtained using multi-step chromatography separation techniques (such as silica gel column chromatography and reversed-phase high-performance liquid chromatography). In the extraction process, parameters such as solvent polarity, extraction time, and temperature have a significant impact on product yield and purity. In recent years, the application of green and efficient technologies such as ultrasound-assisted extraction and microwave-assisted extraction has further optimized the extraction process of this compound, improving extraction efficiency and environmental friendliness. In addition, structural identification mainly relies on modern analytical methods such as nuclear magnetic resonance (NMR), mass spectrometry (MS), and infrared spectroscopy (IR) to ensure the accuracy of compound structures.

Pharmacological activity research

4-Demethyl Surmanethine B exhibits significant antiproliferative and pro-apoptotic activity in various tumor cell lines, especially exhibiting strong cytotoxicity in liver cancer cells. In vitro cell experiments have shown that this compound can inhibit the proliferation, migration, and invasion of liver cancer cells, inducing cell cycle arrest and apoptosis. Animal model studies further confirmed its in vivo inhibitory effect on liver cancer tumor growth, with low toxic side effects and good safety. Mechanistic studies have shown that 4-desmethyl Humbertine B achieves its anti-tumor effects by regulating multiple signaling pathways, including inhibiting abnormal activation of STAT3, reducing anti-apoptotic expression of BCL2, and suppressing TOP1-mediated DNA repair processes, thereby promoting cancer cell apoptosis. Additionally, its regulation of signaling molecules such as MAPK1, PIK3CA, and EGFR helps inhibit tumor cell proliferation and metastasis. Overall, 4-desmethyl Temporamine B has multi-target, multi-mechanism anti-tumor potential.

Mechanism of action and molecular targets

The anti-liver cancer effects of 4-desmethyl Temporrine B involve several key molecular targets. First, the BCL2 family proteins, as key regulators of cell apoptosis, have downregulated their expression to promote tumor cell apoptosis. 4-Demethyl Turpentine B significantly inhibits BCL2 expression, disrupting the anti-apoptotic barrier of tumor cells. Second, the STAT3 signaling pathway plays a central role in the development of liver cancer. This compound inhibits STAT3 phosphorylation, blocks its transcriptional activity, and suppresses tumor cell proliferation and immune escape. TOP1 acts as a DNA topoisomerase, participating in DNA replication and repair. 4-Demethyl Humantine B inhibits TOP1 activity, induces DNA damage, and promotes cell apoptosis. Regulation of the MAPK1 and PIK3CA signaling pathways further inhibits tumor cell proliferation and migration. The inhibitory effect of TERT helps limit the unlimited proliferation capacity of tumor cells. Reduced MMP9 expression inhibits tumor invasion and metastasis. Regulation of EGFR and PTGS2 involves alterations in the tumor microenvironment and suppression of inflammatory responses. As a tumor suppressor gene, TP53's functional recovery helps inhibit tumor cell apoptosis and growth. In summary, 4-demethyl Surmantoine B achieves comprehensive inhibition of liver cancer cells through multi-target synergistic action.

Druggability evaluation and pharmacokinetics

Druggability is a key link in the development of natural product drugs. 4-Demethyl Temporazine B shows good drug compatibility in terms of physicochemical properties. The LogP is about 2, indicating moderate lipid solubility, which is beneficial for oral absorption and cell membrane penetration. The TPSA value is moderate, indicating good bioavailability and cell permeability. Moderate water solubility, which is beneficial for formulation development. The high blood-brain barrier penetration ability suggests possible central nervous system-related pharmacological activity, but potential central toxicity risks should also be considered. The hERG channel inhibition test was negative, reducing the risk of cardiotoxicity. Ames trial results showed that it carries a low risk of genotoxicity and is relatively safe. Pharmacokinetic studies have shown that this compound has good stability and an appropriate half-life in vivo, maintaining effective plasma drug concentrations. Metabolic pathways mainly involve hepatic enzyme systems, and the safety of these metabolites requires further evaluation. Overall, 4-demethyl Temporamine B has a solid druggability foundation and is suitable for further preclinical development.

Prospects and outlooks for clinical applications

As one of the world's most important malignant tumors, liver cancer currently has treatment options including surgical resection, radiotherapy, chemotherapy, and targeted therapy, but these have limited efficacy and significant side effects. 4-Demethyl Desturangine-B, with its multi-target and multi-mechanism antitumor effects, offers new ideas for liver cancer treatment. Its excellent pharmacokinetic properties and safety lay the foundation for clinical application. Future research should further clarify its mechanism of action, optimize dosage forms and administration regimens, conduct systematic toxicological and pharmacodynamic evaluations, and promote its entry into clinical trial stages. Moreover, combining modern molecular targeting technologies with nano drug delivery systems to enhance targeting and efficacy and reduce side effects is also an important direction for future research. The potential applications of 4-desmethyl uncyclophylline B in tumors and diseases beyond liver cancer are also worth exploring, especially its ability to penetrate the blood-brain barrier, suggesting its potential value in neurological diseases.

Conclusion

4-Demethyl Humantine B, a hydroxyindole alkaloid derived from Gelsemium rankinii, shows broad prospects for drug development due to its unique chemical structure and multi-target anti-liver cancer activity. Its excellent physicochemical properties, druggability, and safety provide strong support for its clinical translation. In the future, through in-depth pharmacological mechanism research, optimization of drug formulations, and systematic preclinical evaluations, it is expected to be developed into a novel natural drug for treating liver cancer, benefiting a wide range of patients. At the same time, research on this compound will also promote the development of natural product pharmacology, promote the rational utilization of natural product resources, and facilitate the discovery of innovative drugs.