Product name: Isotoosendanin
Synonym name: Isochuanliansu
Catalogue No.: BP4288
Cas No.: 97871-44-8
Formula: C₃₀H₃₈O₁₁
Mol Weight: 574.623
Botanical Source:
Type of Compound:

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

Isotoosendanin, CAS number 97871-44-8, is a bioactive compound derived from natural plants that has attracted widespread attention in recent years due to its multi-target pharmacological activity. As an orally active TGFβR1 inhibitor, isotritin shows potential clinical value in tumor suppression, anti-inflammation, and antiparasitic fields. Especially in the treatment of malignant tumors such as triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC), isotrutin demonstrates significant antitumor activity by regulating key cellular signaling pathways and inhibiting tumor cell migration, invasion, and metastasis. Moreover, its regulatory effect on inflammatory responses also provides a theoretical basis for its application in inflammatory diseases. This paper systematically reviews the chemical structure and physicochemical properties of heteroteronin (heteroteron), plant origin and extraction methods, pharmacological activity, mechanism of action, druggability evaluation, and clinical application prospects, aiming to provide scientific evidence for in-depth research and development of this natural product.

Chemical structure and physicochemical properties

Isochuanneemin is a natural product with a molecular weight of 574.6230, featuring a complex chemical structure that includes multiple cyclic structures and various functional groups, giving it unique biological activity. Its LogP value is 1.1807, indicating moderate lipid solubility, which facilitates cell membrane penetration and oral absorption. The polar surface area (TPSA) is 169.8 Ų, reflecting a high polarity characteristic and suggesting limited solubility in aqueous media (about 0.0716), which may affect its bioavailability. Heterolin lacks the ability to penetrate the blood-brain barrier, reducing the risk of central nervous system toxicity. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames mutagenic test result was 0.0, indicating a low genotoxicity risk and meeting the basic safety evaluation requirements. These physicochemical and toxicological parameters lay a solid foundation for the drug development of heteroterin.

Plant Origins and Extraction Methods

Isocortin is mainly found in plants of the Melia family, especially in the root bark and leaves of Melia species. Neem plants are widely used in traditional Chinese medicine, with effects such as clearing heat and detoxifying, dispelling wind, and relieving pain. The extraction of isocortex is usually done by organic solvent extraction combined with column chromatography separation. The specific process includes the following steps:

1. Raw material preparation: Select dried root bark or leaves of the Chinese chinaberry genus and crush into fine powder.
2. Solvent extraction: Multiple reflux extractions are performed using ethanol or methanol to improve extraction yield.
3. Concentration and separation: The extract is concentrated to an appropriate volume and separated and purified using silica gel column chromatography or high-performance liquid chromatography (HPLC).
4. Purity identification: Confirm the structure and purity of xenocortex using mass spectrometry (MS), nuclear magnetic resonance (NMR), and other technologies.

In recent years, the application of ultrasound-assisted extraction and microwave-assisted extraction technologies has significantly improved the extraction efficiency and purity of heterocortin, providing technical support for its industrial production.

Pharmacological activity research

The pharmacological activities of heteronerin cover antitumor, anti-inflammatory, and antiparasitic properties, demonstrating a wide range of biological effects.

Antitumor activity

As a TGFβR1 inhibitor, isotrutin effectively inhibits its kinase activity (IC50 = 6732 nM) and blocks the TGF-β signaling pathway. TGF-β signaling plays a key role in the occurrence and development of various tumors, especially in triple-negative breast cancer (TNBC), where TGF-β-induced cell migration and invasion are the main mechanisms of tumor metastasis. Isotritin directly targets the SHP-2 protein, enhancing its stability and reducing ubiquitination, thereby inhibiting the JAK/STAT3 signaling pathway and blocking the migration and invasion ability of tumor cells. In the TNBC xenograft model and the A549 non-small cell lung cancer xenograft model, isoguaranin significantly inhibited tumor growth and metastasis, indicating good antitumor potential.

Anti-inflammatory activity

Isotritin demonstrated significant anti-inflammatory effects in acetic acid-induced vascular permeability and lambda-carrageenan-induced hind paw edema in animal models, suggesting that it can regulate the release of inflammatory mediators and the activity of inflammatory cells, reduce tissue edema, and increase vascular permeability. This characteristic gives it potential application value in the treatment of inflammation-related diseases.

Antiparasitic activity

Although isotritin is not the main research focus, it shows certain inhibitory effects on various parasite-related targets such as PFCRT, DHFR, and CYP51, indicating its potential in the antiparasitic field and warranting further in-depth research.

Mechanism of action and molecular targets

The mechanism of action of isoproterine mainly regulates key intracellular signaling pathways.

TGFβR1 kinase inhibition

As an inhibitor of TGFβR1, isotritin can inhibit its kinase activity and block the activation of the TGF-β signaling pathway. The TGF-β signaling pathway plays an important role in cell proliferation, differentiation, migration, and immune regulation, and its abnormal activation is closely related to tumor metastasis. By inhibiting TGFβR1, isoguaranin effectively blocks downstream signal transduction, suppressing tumor cell migration and invasion.

SHP-2 protein stability is enhanced

Isoplanin directly targets SHP-2 (Src homologous domain contains protein tyrosine phosphatase-2), enhancing its protein stability and reducing ubiquitin degradation. SHP-2 plays a regulatory role in cell signaling and is involved in the activity regulation of the JAK/STAT3 pathway. By stabilizing SHP-2, isoproterine inhibits the JAK/STAT3 signaling pathway, blocking tumor cell proliferation and metastasis signals.

JAK/STAT3 signaling pathway inhibition

The JAK/STAT3 pathway is a key pathway for the growth and immune escape of various tumor cells. Isotritin regulates SHP-2 activity, inhibits signaling in this pathway, reduces STAT3 phosphorylation levels, and thereby suppresses tumor cell proliferation and migration.

Anti-inflammatory mechanism

Isocortezin reduces inflammatory responses by inhibiting the release of inflammatory mediators and regulating immune cell function. Its specific molecular mechanisms still require further elucidation but are closely related to its regulation of signaling pathways.

Druggability evaluation and pharmacokinetics

The druggability parameters of isocortezin indicate that it has certain potential for drug development:

• Molecular weight: 574.6230, slightly above the ideal drug molecular weight range, but still within acceptable limits.
• Lipophilic (LogP): 1.1807, moderate, beneficial for oral absorption and internal distribution.
• Polar surface area (TPSA): 169.8 Ų, which is relatively high and may limit its cell membrane permeability and oral bioavailability.
• Water solubility: 0.0716, which is relatively low, suggesting that formulation optimization is needed to improve solubility.
• Blood-brain barrier penetration: low, reduces risk of central nervous system side effects.
• hERG channel inhibition: None, low risk of cardiotoxicity.
• Genotoxicity (Ames test): Negative, relatively safe.

Currently, pharmacokinetic (PK) data on isotritin are limited. Preliminary in vivo experiments show it has good oral activity and a certain half-life, but further systematic studies are needed on its absorption, distribution, metabolism, and excretion (ADME) characteristics to guide clinical formulation design and administration regimens.

Prospects and outlooks for clinical applications

Isoterelin shows broad application prospects in anti-tumor, anti-inflammatory, and antiparasitic fields. Especially in the treatment of triple-negative breast cancer and non-small cell lung cancer, heteronerin regulates tumor cell signaling pathways through multiple targets, inhibiting tumor invasion and metastasis, showing potential as a novel targeted drug. Moreover, its remarkable anti-inflammatory effects provide new ideas for the treatment of inflammatory diseases.

Future research should focus on the following directions:

1. Pharmacokinetics and toxicology research: Systematic evaluation of the in vivo behavior and safety of heterocortin to provide a basis for clinical trials.
2. Structural optimization and derivative development: Chemical modification enhances water solubility, bioavailability, and targeting, enhancing efficacy and safety.
3. In-depth mechanism analysis: Further elucidates the molecular mechanisms of its effects on signaling pathways and immune regulation, uncovering more potential targets.
4. Preclinical and clinical research: Conduct animal models and clinical trials to verify efficacy and safety, and promote their transformation into clinical drugs.

Conclusion

As a versatile natural product, heteronerein demonstrates significant potential in anti-tumor and anti-inflammatory fields due to its unique molecular structure and multi-target pharmacological activity. It exerts antitumor effects by inhibiting TGFβR1 kinase activity and regulating the SHP-2/JAK/STAT3 signaling pathway, while also exhibiting good safety and oral activity. Although research on its pharmacokinetics and clinical applications is still in its early stages, isocretin undoubtedly provides an important candidate molecule for the development of natural product drugs. In the future, through in-depth mechanistic research and drug optimization, Yichuanneemin is expected to become a novel drug for treating malignant tumors and inflammatory diseases, offering new treatment options for patients with related conditions.