Product name: Ganoderenic acid K
Synonym name:
Catalogue No.: BP2273
Cas No.: 942950-94-9
Formula: C₃₂H₄₄O₉
Mol Weight: 572.695
Botanical Source: Ganoderma
Type of Compound: Triterpenoids

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.

HPLC of Ganoderenic acid K

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

Introduction/Overview

Ganoderma lucidum, as a traditional Chinese medicinal herb, has attracted attention for its abundance of triterpenoids and polysaccharide active components. Ganoderenic acid K is an important triterpene natural product isolated from the fruiting body of Ganoderma, exhibiting significant biological activity, especially in regulating cholesterol metabolism and showing potential pharmacological value against tumors. In recent years, with in-depth research into the molecular mechanisms of Multiple Myeloma (MM), Ganoderma alekate K has become a research hotspot due to its regulatory effects on multiple key tumor-related targets. This paper will systematically review the chemical structure and physicochemical properties of Ganoderma enic acid K, plant origin and extraction methods, pharmacological activity, mechanism of action and molecular targets, druggability evaluation, and clinical application prospects, aiming to provide a theoretical foundation and research direction for drug development of this natural product.

Chemical structure and physicochemical properties

Ganoderma enic acid K has the molecular formula C_30H_44O_10 and a molecular weight of 572.6950, making it a member of the Ganoderma triterpene compounds. Its structural features include a polycyclic triterpene backbone with multiple hydroxyl and carboxyl functional groups, giving it high polarity. In terms of physicochemical properties, the LogP value of Ganoderma enic acid K is 2.4834, indicating moderate lipid solubility that facilitates cell membrane penetration. Its topological pole surface area (TPSA) is 155.27 Ų, and its high pole surface area suggests strong polarity and hydrogen bonding ability, which may affect its bioavailability and ability to cross the blood-brain barrier. Low water solubility (0.0373 mg/mL) suggests limited solubility in the aqueous phase, suggesting that drug formulation techniques may be needed to improve its elution performance. Low blood-brain barrier permeability indicates limited distribution in the central nervous system. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames mutagenicity test result was 0.0, indicating a low genotoxicity risk and a solid safety foundation.

Plant Origins and Extraction Methods

Ganoderma enic acid K mainly comes from the fruiting body of Ganoderma lucidum. Ganoderma is a fungus of the genus Ganoderma in the Polypore family, widely distributed in temperate and subtropical regions of Asia. The fruiting body of Ganoderma lucidum is rich in various triterpene compounds, with Ganoderma alekate K being one of the important active components. Traditional extraction methods mostly use organic solvent extraction combined with column chromatography for separation and purification. The typical process generally includes: crushing the dried Ganoderma lucidum fruiting bodies, performing multiple reflux extracts using ethanol or methanol, separating and purifying the extract using a silica gel column or C18 reversed phase column, and finally performing purity testing and structural identification by high-performance liquid chromatography (HPLC). Modern extraction technologies such as ultrasonic-assisted extraction and microwave-assisted extraction are also applied to improve the extraction efficiency and purity of Ganoderma enic acid K. In addition, the structural identification of Ganoderma enic acid K mainly relies on multiple analytical methods such as nuclear magnetic resonance (NMR), mass spectrometry (MS), and infrared spectroscopy (IR).

Pharmacological activity research

Ganoderma enic acid K exhibits significant pharmacological effects across various biological activities, especially for its inhibition of HMG-CoA reductase (HMGCR). HMGCR is a rate-limiting enzyme in cholesterol biosynthesis. Ganoderma enoic acid K has an IC50 of 16.5 μM, showing strong inhibitory activity, suggesting its potential in regulating blood lipids and preventing cardiovascular diseases. In addition, Ganoderma enic acid K has also shown positive effects in anti-tumor research, especially in cell models of multiple myeloma, where it can regulate tumor cell proliferation, apoptosis, and signaling pathways through multiple targets.

In vitro experiments, Ganoderma enylic acid K can inhibit the proliferation of multiple myeloma cells, induce apoptosis, and suppress the activation of tumor-related signaling pathways. Its anti-inflammatory and immunomodulatory effects also provide auxiliary support for its anti-tumor activity. Animal model studies further confirmed the potential of Ganoderma Enoic Acid K to slow tumor growth and improve immune function.

Mechanism of action and molecular targets

Multiple myeloma is a malignant plasma cell disease whose development involves multiple signaling pathways and various key molecules. Ganodermalic acid K exerts antitumor effects through a multi-target mechanism, with main targets including BCL2, STAT3, TOP1, TP53, NFKB1, AKT1, BRAF, NRAS, CDKN2A, and CXCR4.

• BCL2: As an anti-apoptotic protein, inhibition of BCL2 helps promote tumor cell apoptosis. Ganoderma enic acid potassium can downregulate BCL2 expression and enhance apoptosis signaling.
• STAT3: The STAT3 signaling pathway plays a key role in tumor cell growth and immune evasion. Ganoderma enic acid K inhibits STAT3 phosphorylation, blocking its transcriptional activation function.
• TOP1: Topoisomerase I (TOP1) participates in DNA replication and transcription; Ganoderma enic acid K may influence tumor cell proliferation by regulating TOP1 activity.
• TP53: As a tumor suppressor gene, TP53's activation promotes cell cycle arrest and apoptosis. Ganoderma enic acid K may enhance tumor cell apoptotic responses by modulating the TP53 pathway.
• NFKB1: The NF-κB signaling pathway is highly active in inflammation and tumors. Ganoderma enic acid K inhibits NFKB1 activity and reduces the expression of pro-tumor inflammatory factors.
• The AKT1:P I3K/AKT pathway is an important signaling pathway for cell survival and proliferation. Ganoderma enic acid K suppresses tumor cell growth by inhibiting AKT1 activation.
• BRAF and NRAS: These two proteins are important components of the MAPK signaling pathway, and Ganoderma enic acid K may influence cell proliferation and differentiation by regulating its activity.
• CDKN2A: Cell cycle regulatory factor. Ganodermic acid K may induce cell cycle arrest by modulating CDKN2A expression.
• CXCR4: Closely related to tumor cell migration and interactions with the bone marrow microenvironment, regulating CXCR4 with Ganoderma enic acid K helps suppress tumor metastasis.

In summary, Ganodermalic acid K regulates tumor cell proliferation, apoptosis, and microenvironment through multi-target and multi-pathway synergistic effects, demonstrating a complex and effective anti-tumor mechanism.

Druggability evaluation and pharmacokinetics

The druggability evaluation of Ganoderma enic acid K indicates that it has certain potential for drug development. Although the molecular weight of 572.7 is slightly higher than the 500 recommended by Lipinski's rules, its LogP value of 2.48 is moderate, which facilitates cell membrane penetration. A higher TPSA (155.27) may limit oral absorption and blood-brain barrier permeability, consistent with experimental data showing low blood-brain barrier permeability. Low water solubility suggests the need to optimize formulations to improve bioavailability. The hERG channel was negative for inhibition and the Ames test showed no mutagenicity, indicating good safety.

Currently, pharmacokinetic research on Ganoderma enic acid K is relatively limited. Preliminary data indicate it is widely distributed in the body, but its metabolic pathways and clearance mechanisms still require systematic study. Its higher polar functional groups may be metabolized by hepatic metabolic enzymes such as cytochrome P450, and the activity and toxicity of these metabolites also require further evaluation. In the future, systematic in vivo pharmacokinetics and toxicology studies are needed to comprehensively assess the feasibility of clinical application.

Prospects and outlooks for clinical applications

Ganodermalic acid K, as a natural compound with multi-target antitumor activity, shows broad application prospects in adjuvant therapy for malignant tumors such as multiple myeloma. Its inhibitory effect on HMG-CoA reductase also suggests its potential in regulating blood lipids and preventing cardiovascular diseases, potentially becoming a new direction for multifunctional drug development.

Future research should focus on:

1. In-depth mechanism research: Using modern technologies such as genomics and proteomics, systematically elucidating the molecular mechanisms by which Ganoderma Enoic acid K regulates the tumor microenvironment and immune system.
2. Pharmacokinetic and toxicological evaluation: Improving in vivo behavioral and safety data to provide scientific basis for clinical trials.
3. Formulation development: To address issues of poor water solubility and low bioavailability, new drug carriers and delivery systems are developed to increase effective concentrations in vivo.
4. Preclinical and clinical research: Conduct efficacy validation of multiple myeloma and related tumor models, gradually advance clinical trials, and evaluate the safety and efficacy of monotherapy or combination therapy.

In addition, the synergistic effects of Ganodermic Acid K with existing antitumor drugs and its role in immune regulation are also key research directions for future research.

Conclusion

Ganodermalic acid K, an important triterpene active ingredient in Ganoderma lucidum, demonstrates excellent pharmacological activity and drug potential due to its significant inhibitory activity against HMG-CoA reductase and multiple regulation of multiple myeloma-related targets. Its complex mechanism of action, multi-target characteristics, and good safety profile lay the foundation for its development as a new drug for anti-tumor and cardiovascular disease treatments. In the future, through systematic pharmacology, pharmacokinetics, and clinical research, Ganoderma Enic Acid K is expected to move from the laboratory to clinical practice and become an important representative in the field of natural product drug research.