Product name: Ingenol
Synonym name:
Catalogue No.: BP0765
Cas No.: 30220-46-3
Formula: C₂₀H₂₈O₅
Mol Weight: 348.439
Botanical Source: Euphorbia lathyris L
Physical Description:
Type of Compound: Diterpenoids

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.




Chengdu Biopurify Phytochemicals Ltd. is a leading company in the research, development, manufacture and marketing of High Quality Phytochemicals and Extracts(especially Active Ingredients from Traditional Chinese Medicine，TCM), Natural Active Pharmaceutical Ingredients worldwide.
The main services:
A. Supply active ingredients and reference standards of TCM, from mgs to kgs scale
B. Custom extraction and purification, target Herb Active Ingredients
C. Custom synthesis and semi-synthesis for Natural Active Ingredients
D. CR(contract research), CM(contract manufacture) and PD(process development) services from lab scale, pilot scale to commercial scale(GMP is also available)
E. TCM compounds library for drug screen,more than 3000 compounds available, many of them are rare and unique.

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

Introduction/Overview

Ingenol, CAS number 30220-46-3, is a tetracyclic diterpene natural product derived from the genus Ingenol. Due to its unique chemical structure and remarkable biological activity, it has attracted widespread attention in the field of natural product pharmacology in recent years. As an activator of protein kinase C (PKC), Macroterol exhibits multiple pharmacological activities, especially showing potential therapeutic value in the anti-tumor field. It has inhibitory effects on various tumor cell lines including prostate cancer, and acts by regulating multiple signaling pathways, making it one of the key compounds for studying new cancer treatment strategies.

This paper will systematically review the chemical structure and physicochemical properties of Giant Alpha Ol, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics, and explore its clinical application prospects and future research directions, aiming to provide theoretical basis and reference for scientific research and drug development in related fields.

Chemical structure and physicochemical properties

Giant terpene is a tetracyclic diterpene compound with a complex cyclic terpene skeleton. Its chemical structure is described as 1a,2,5,5a,6,9,10,10a-octahydro-1H-2,8a-methanocyclopenta[a]cyclopropa[e][10]annulen-11-one, with a molecular formula of C20H28O5 and a molecular weight of 348.4390. Structurally, Macroalpha is replaced by hydroxyl groups at positions 5, 5a, and 6; methyl groups at positions 1, 1, 7, and 9; hydroxymethyl groups at position 4; and oxygen group group at position 1. Its stereochemical configuration is 1aR, 2S, 5R, 5aR, 6S, 8aS, 9R, and 10aR, demonstrating high stereoselectivity.

In terms of physicochemical properties, the LogP value of Giant Alpha Alcohol is 1.4461, indicating moderate lipid solubility that facilitates cell membrane penetration. The total polar surface area (TPSA) is 97.99 Ų, indicating moderate polarity and favorable binding to biomacromolecules. Water solubility is 0.9142 mg/mL, classifying it as a low-solubility compound, suggesting that solubility improvement strategies should be considered in drug formulation development. Its lower blood-brain barrier permeability reduces the risk of central nervous system toxicity. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames test result was 0.0, indicating no significant mutagenicity.

Plant Origins and Extraction Methods

Euphorbia spp. is mainly found in plants of the genus Euphorbia spp., especially species such as Euphorbia peplus and Euphorbia tirucalli. Plants of this genus are widely distributed in tropical and subtropical regions and have long been used in traditional medicine to treat skin diseases and tumors.

Common methods for extracting Giant Alpha Alcohol include solvent extraction, column chromatography separation, and high-performance liquid chromatography (HPLC) purification. Ethanol or methanol is generally used as the preliminary extraction solvent, with ultrasound-assisted extraction or reflux extraction improving extraction efficiency. The crude extract was separated by silica gel column chromatography and combined with thin-layer chromatography (TLC) monitoring, further purified to obtain high-purity Macroethyl Ol. In recent years, supercritical fluid extraction and membrane separation technologies have also been applied to improve extraction efficiency and purity.

Moreover, with the development of synthetic biology and chemical synthesis technologies, the total and semi-synthesis methods for Giant Alpha Alcohol have gradually matured, making large-scale production possible.

Pharmacological activity research

As a PKC activator, Macroterol exhibits multiple biological activities, with particularly in-depth research in the anti-tumor field. Its main pharmacological activities include:

1. Antitumor activity
   Macroterol has inhibitory effects on various tumor cell lines, especially prostate cancer cells. In vitro experiments have shown that it can inhibit tumor cell proliferation, induce apoptosis, and block the cell cycle process. Its antitumor effect is partly attributed to the activation of PKCs, which in turn regulate downstream signaling pathways such as MAPK and STAT3, affecting cell survival and proliferation.

2. Immunomodulatory effects
   By activating PKC, Macroterol can regulate immune cell function and promote immune responses. Research shows that it can enhance the activity of macrophages and T cells, and improve anti-tumor immune responses.

3. Antiviral activity
   Some studies have found that Macroethyl has inhibitory effects on certain viruses, possibly blocking viral replication by modulating host cell signaling pathways.

4. Potential for treating skin diseases
   Macrocephal derivatives have been used to treat skin cancer and psoriasis, showing good local application effects.

Mechanism of action and molecular targets

The core mechanism of action of Macroethyl is to regulate intracellular signaling by activating members of the PKC family. PKC is an important class of serine/threonine protein kinases involved in regulating cell proliferation, differentiation, apoptosis, and immune responses.

In prostate cancer, the key molecular targets of the effects of giant alpha alcohol include:

• BCL2: An anti-apoptotic protein, Macroalpha promotes tumor cell apoptosis by regulating its expression.
• PTPN1: Protein tyrosine phosphatase, involved in signal transduction regulation, affecting cell proliferation.
• STAT3: Signal transduction and transcription activator factor 3, regulating tumor cell survival and immune escape.
• ESR2: Etrogen receptor β involved in the regulation of hormone-dependent tumors.
• ABCB1: Multidrug resistance-associated protein, Macroterell may reverse tumor resistance by regulating its expression.
• NFE2L2: Antioxidant response regulator, modulating cellular oxidative stress responses.
• MAPK1: Mitogen-activated protein kinase, involved in cell proliferation and differentiation signal transduction.
• CASP9: Caspase 9, a key enzyme executing apoptosis.
• CYP19A1: Aromatase, involved in hormone metabolism.
• AR: Androgen receptor, an important regulatory factor for prostate cancer.

Macroterol regulates the expression and activity of these targets through PKC activation, thereby affecting tumor cell growth, apoptosis, and drug resistance. Additionally, PKC activation can promote changes in intracellular calcium ion concentration, regulate cytoskeletal reorganization and migration capacity, and influence tumor metastasis.

Druggability evaluation and pharmacokinetics

The drugability of Giant Alpha Alcohol demonstrates certain advantages and challenges:

• Molecular weight and lipid solubility: molecular weight 348.4390, LogP 1.4461, conforming to Lipinski's rules, favorable for oral absorption.
• Polarity and solubility: TPSA is 97.99 Ų, with low water solubility (0.9142 mg/mL), indicating the need to optimize solubility in formulation design to improve bioavailability.
• Blood-brain barrier permeability: Low permeability reduces the risk of central nervous system side effects but limits the use of brain diseases.
• Safety: hERG channel inhibition negative, reducing the risk of cardiotoxicity; Ames test was negative, indicating no significant mutagenicity and good safety.
• Metabolic stability and excretion: Currently, metabolic and pharmacokinetic data on macroterinol are limited. Preliminary studies show that it is metabolized in the liver via the CYP450 enzyme system, with a moderate half-life and is mainly excreted by the kidneys.

In the future, further systematic pharmacokinetic studies are needed, including evaluation of absorption, distribution, metabolism, and excretion (ADME) characteristics, as well as toxicological studies, to improve the druggability evaluation system.

Prospects and outlooks for clinical applications

As a naturally derived PKC activator, Giant Alpha Alcohol has significant anti-tumor potential, especially showing unique advantages in the treatment of prostate cancer. Through multi-target and multi-pathway synergistic effects, it overcomes the limitations of traditional single-target drugs and has broad clinical application prospects.

Currently, Giant Alpha Alcohol and its derivatives have entered partial preclinical research stages, and some formulations have shown good efficacy for the treatment of topical skin diseases. Future research directions include:

• Structural modification and derivatives development: Chemical modification enhances water solubility, bioavailability, and targetability, optimizing efficacy and safety.
• Combination therapy strategy: Combined with existing antitumor drugs to enhance efficacy and overcome resistance.
• Nanocarriers and targeted delivery: Using nanotechnology to enhance the in vivo stability and targeting of Giant Alpha Alcohol, reducing side effects.
• Clinical trial advancement: Systematically conduct Phase I/II clinical trials to verify safety and efficacy, and promote clinical translation.
• Expansion of multiple disease indications: Beyond tumors, explore its potential applications in immune regulation, antiviral, and inflammatory diseases.

Conclusion

Giant Alpha Alcohol, a unique tetracyclic diterpene natural product, demonstrates great potential as a novel antitumor drug due to its unique chemical structure and multi-target pharmacological activity. It regulates multiple signaling pathways through PKC activation, affecting tumor cell proliferation, apoptosis, and drug resistance, providing new ideas for tumor treatment.

Although there are still certain challenges in extraction and purification, pharmacokinetics, and clinical applications, with the development of modern medicinal chemistry, molecular biology, and pharmaceutical technologies, the research and application prospects for Juju Alpha Alcohol are broad. Future in-depth mechanistic research, structural optimization, and clinical validation will drive Giant Alpha Alcohol from the laboratory to clinical practice, benefiting more patients.