Product name: Homoharringtonine
Synonym name: Omacetaxine mepesuccinate
Catalogue No.: BP0732
Cas No.: 26833-87-4
Formula: C₂₉H₃₉NO₉
Mol Weight: 545.629
Botanical Source: Cephalotaxus fortunei Hook. f.
Physical Description:
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.




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The main services:
A. Supply active ingredients and reference standards of TCM, from mgs to kgs scale
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HNMR of Homoharringtonine

HPLC of Homoharringtonine

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

Introduction/Overview

Homoharringtonine (HHT) is a natural compound with significant antitumor activity, originally isolated from plants of the genus Homoharringtonine. As a cytotoxic alkaloid, HHT exerts its anticancer effect by inhibiting protein translation and extending the stage, showing unique efficacy especially in leukemia treatment. In recent years, with the deepening of molecular biology and pharmacological research, the mechanism, molecular targets, and druggability characteristics of high-tristaxyl ester alkali have been systematically elucidated, providing a solid scientific foundation for its clinical application. This paper aims to comprehensively review the chemical structure, plant origin, pharmacological activity, mechanism of action, druggability, and clinical application prospects of high-triperate ester alkaloid, aiming to provide a reference for the fields of natural product pharmacology and antitumor drug development.

Chemical structure and physicochemical properties

The molecular formula of high-stalkyl methale is C29H39NO9, with a molecular weight of 545.6290 and CAS number 26833-87-4. Its chemical structure belongs to the alkaloid class, featuring a complex terpene backbone and multiple hydroxyl and ester functional groups. The structure contains multiple chiral centers, giving it a high degree of stereoselectivity. The LogP value of HHT was 2.2768, indicating moderate lipid solubility, which facilitates membrane penetration. The polar surface area (TPSA) is 123.9900, indicating that the molecule has a certain polarity, affecting its water solubility and bioavailability. Water solubility is relatively low, about 0.2827 mg/mL, suggesting that solubility needs to be optimized in drug formulations to improve bioavailability. This compound has low blood-brain barrier permeability, 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 scored 0.0, indicating a low genotoxicity risk and meeting safety requirements.

Plant Origins and Extraction Methods

The main source of high tricaraxe ester is Cephalotaxus spp., with the high content in Cephalotaxus harringtonia. Plants of this genus are distributed in East Asia and have traditionally been used in traditional Chinese medicine. HHT extraction typically uses organic solvent extraction combined with multi-step chromatography separation technology. The classic extraction process includes:

1. Raw material preparation: collect the bark or branches and leaves of the three-pointed cedar, dry and crush them.
2. Extraction by leaching: Using organic solvents such as methanol, ethanol, or ethyl acetate to dissolve the target alkaloid.
3. Concentration and separation: After the extract is concentrated by rotary evaporation, impurities are removed by liquid-liquid distribution.
4. Chromatographic purification: HHT is purified by silica gel column chromatography, reversed-phase high-performance liquid chromatography (RP-HPLC), and other methods.
5. Crystallization: Purified HHT is crystallized by solvent to obtain high-purity products.

In recent years, with the promotion of green chemistry concepts, supercritical fluid extraction and microwave-assisted extraction technologies have also been tried for HHT extraction, improving extraction efficiency and environmental friendliness.

Pharmacological activity research

As an antitumor drug, high-triperate ester alkaloid has shown remarkable efficacy, especially in the treatment of leukemia. Its pharmacological activity is mainly reflected in the following aspects:

1. Antileukemic activity
   HHT exhibits cytotoxicity against various leukemia cell lines, including acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Clinical studies have shown that HHT can induce apoptosis of leukemia cells, inhibit cell proliferation, and improve patient survival rates.

2. Induces apoptosis
   HHT promotes apoptosis by regulating multiple intracellular signaling pathways. Its mechanism involves downregulation of anti-apoptotic proteins MCL1 and BCL2, activating mitochondria-dependent apoptosis pathways.

3. Inhibits tumor stem cells
   Research shows that HHT can target leukemia stem cells, reducing their self-renewal ability and lowering the risk of relapse.

4. Multidrug resistance
   HHT is active against multidrug-resistant leukemia cells, overcoming resistance to traditional chemotherapy drugs and enhancing treatment outcomes.

5. Other tumor types
   Although mainly used for leukemia, HHT's antitumor activity in solid tumors such as lung and breast cancer has also been gradually reported, showing broad application potential.

Mechanism of action and molecular targets

The antitumor effect of hypertrismethylethyl ester mainly achieves by inhibiting the translational extension phase of protein synthesis. Its specific mechanisms include:

1. Suppresses translation extension
   HHT binds to ribosomes, blocking the peptide chain lengthening process, leading to hindered synthesis of new proteins, disrupted cell function, and ultimately induce cell death.

2. Regulation of key molecular targets

3. AMPK (PRKAA1): HHT activates the AMPK signaling pathway, promotes regulation of cellular energy metabolism, and induces autophagy and apoptosis.
4. MCL1, BCL2: HHT downregulates the expression of anti-apoptotic proteins MCL1 and BCL2, disrupts cell survival signals, and promotes apoptosis.
5. NOTCH1: Inhibits the NOTCH1 signaling pathway, preventing abnormal differentiation and proliferation of leukemia cells.
6. STAT3: Inhibits STAT3 activity and reduces the expression of genes that promote survival and proliferation.
7. MAPT: Affects microtubule-associated protein MAPT, interfering with cytoskeletal stability.
8. IDH1: Regulates the metabolic enzyme IDH1, affecting cellular metabolic status.
9. NFE2L2: Regulates the antioxidant transcription factor NFE2L2, affecting cellular redox balance.
10. TOP1: Inhibits TOP1 of topoisomerase and affects DNA replication and transcription.

11. SIRT1: Regulates the deacetylase SIRT1, involved in cellular stress responses and metabolic regulation.

12. Multi-target synergistic effect
    HHT regulates tumor cell survival, proliferation, and apoptosis through multi-target and multi-pathway synergistic regulation, overcoming resistance issues of single-target drugs and improving treatment outcomes.

Druggability evaluation and pharmacokinetics

Homo Triscapal Ester Soda possesses excellent druggability characteristics:

• Moderate molecular weight, compliant with Lipinski rules, facilitates drug absorption and distribution.
• Moderate lipid solubility (LogP=2.2768) favors cell membrane penetration, but low water solubility requires pharmaceutical improvement.
• Polar surface area (TPSA=123.99), indicating moderate polarity, which is favorable for binding with biological macromolecules.
• The blood-brain barrier has low permeability, reducing the risk of central nervous system toxicity.
• No hERG channel suppression, reducing the risk of cardiotoxicity.
• Non-genotoxic (Ames test negative), relatively safe.

In terms of pharmacokinetics, HHT has low oral bioavailability and is mainly administered by subcutaneous injection or intravenous infusion. It is widely distributed in the body, metabolized mainly through hepatic enzyme systems, has a moderate half-life, and is convenient for clinical dose adjustment. Its clearance rate and the toxicity of its metabolites are both within controllable ranges.

Prospects and outlooks for clinical applications

Glyceridesterine, as an antileukemia drug, has been approved in multiple countries for the treatment of patients with chronic myeloid leukemia (CML) resistance or those intolerant to tyrosine kinase inhibitors (TKIs). Clinical data show that HHT combined with other chemotherapy drugs can significantly improve response rates and survival times.

Future clinical application focuses include:

• Optimizing Administration Regimens: Developing oral or long-acting sustained-release formulations to improve patient compliance.
• Combination treatment strategies: Combined with targeted drugs and immunotherapies to overcome resistance and enhance efficacy.
• Expanding indications: Exploring the potential of HHT in other hematologic malignancies and solid tumors.
• Biomarker screening: Identify molecular markers that predict efficacy and drug resistance to achieve precise medication.
• Safety monitoring: Long-term follow-up to assess toxic side effects to ensure patient safety.

In addition, the design and synthesis of derivatives based on HHT structures are actively advancing, aiming to enhance activity, reduce toxicity, improve pharmacokinetic performance, and drive the development of next-generation anti-tumor drugs.

Conclusion

As a natural antitumor drug, high tristaxyl ester alkaloid has made significant progress in leukemia treatment due to its unique mechanism of action and multi-target regulatory capabilities. Its excellent druggability and safety lay the foundation for clinical application. In the future, with advances in molecular targeting technology and drug design, HHT and its derivatives are expected to play an even greater role in anti-tumor treatments. In-depth research into its mechanism of action, optimization of drug formulations, and combination therapy strategies will promote the broader clinical application of hypertricadane, bringing new hope to cancer patients.