Product name: Halofuginone
Synonym name:
Catalogue No.: BP4353-1
Cas No.: 55837-20-2
Formula: C16H17BrClN3O3
Mol Weight: 414.684
Botanical Source:
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.
HPLC of Halofuginone
HNMR of Halofuginone
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
Halofuginone (CAS No.: 55837-20-2) is a small molecule compound derived from the active ingredient Febrifugine in the traditional Chinese medicine Changshan (Dichroa febrifuga Lour.). As a competitive prolyl-tRNA synthetase (ProRS) inhibitor, Changshan ketone has attracted widespread attention in the field of natural product pharmacology. Its unique biological activities cover multiple effects including antimalarial, anti-inflammatory, anti-cancer, anti-fibrotic, and pulmonary vasodilation, demonstrating promising potential for drug development. In recent years, with deeper elucidation of molecular mechanisms, the mechanisms of Changshan ketone's role in regulating collagen synthesis, inhibiting TGF-β signaling pathways, and modulating ion channels have gradually become clearer, driving research progress in areas such as osteoarthritis, fibrosis, and pulmonary vascular diseases.
This review aims to systematically summarize the chemical structure and physicochemical properties of Changshan ketone, plant origin and extraction methods, pharmacological activity, and mechanism of action. By combining druggability evaluation and pharmacokinetic data, it explores its clinical application prospects and future research directions, providing theoretical basis and reference for natural product pharmacology and new drug development.
The chemical structure of Changshan ketone is based on the framework of Febrifugine, achieving better efficacy and safety through structural modification. Its molecular formula is C20H23ClN2O3, with a molecular weight of 414.6870. Changshan ketone contains a characteristic quinoline ring and chlorinated substituent, giving it unique chemical properties and biological activity.
In terms of physicochemical properties, Changshan ketone has a LogP value of 1.2794, indicating moderate lipid solubility, which is beneficial for cell membrane penetration and distribution in vivo. The polar surface area (TPSA) is 84.22 Ų, indicating a certain affinity for polar environments. Water solubility is 1.7271 (unspecified, usually mg/mL or mol/L), indicating good solubility and facilitating drug formulation development. The blood-brain barrier has high penetration, suggesting its potential role in central nervous system diseases. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames test result was 1.2, indicating a low genotoxicity risk and a solid safety foundation.
The structural characteristics and physicochemical properties of Changshan ketone provide a molecular basis for its multi-target and multi-mechanism pharmacological activity, while also laying a solid foundation for its pharmacokinetic behavior and clinical application.
The parent compound of Changshan ketone, Febrifugine, was originally isolated from Changshan (Dichroa febrifuga Lour.). Changshan is a traditional Chinese medicine mainly distributed in southern China and Southeast Asia. Its rhizomes are rich in dihydroquinoline alkaloids, with febrifugine being one of the main active ingredients.
Traditional extraction methods usually use organic solvents (such as ethanol and methanol) to extract dried Changshan rhizomes, followed by separation and purification through liquid-liquid partitioning and column chromatography. With the development of modern separation technologies, technologies such as supercritical CO2 extraction, high-performance liquid chromatography (HPLC), and reversed-phase chromatography have been introduced, improving extraction purity and efficiency.
Changshan ketone, as a derivative of febrifugine, is usually obtained through chemical or semi-synthetic methods. The synthetic route uses Febrifugine as the starting material, and through chloro-subsating, hydroxyl protection, and deprotection steps, the structurally modified Changshan ketone is obtained. This method not only ensures product purity and batch stability, but also meets the needs of drug development for large-scale production.
The antimalarial activity of Changshan ketone originates from its parent compound Febrifugine. In vitro and in vivo experiments have shown that Changshan ketone has a significant inhibitory effect on Plasmodium spp., effectively reducing parasite load. Its mechanism of action mainly inhibits the protein synthesis and metabolic pathways of malaria parasites, thereby blocking the growth and reproduction of parasites.
Changshan ketone, as a specific inhibitor of type I collagen synthesis, has shown outstanding performance in anti-fibrotic research. Fibrosis is the common pathological basis for various chronic diseases (such as liver fibrosis, pulmonary fibrosis, and renal fibrosis), where excessive collagen deposition leads to tissue hardening and functional impairment. Changshan ketone competitively inhibits proline-tRNA synthase, reducing proline protein synthesis and thereby suppressing excessive collagen production. In addition, Changshan ketone can inhibit the activity of the TGF-β signaling pathway, reducing the process of fibrosis.
Changshan ketone has significant anti-inflammatory activity. Research shows that Changshan ketone can downregulate the expression of various inflammatory mediators, such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and nitric oxide synthase (iNOS), thereby reducing inflammatory responses. Its anti-inflammatory mechanism is closely related to the inhibitory nuclear factor κB (NF-κB) signaling pathway, which can block the transmission of inflammatory signals and reduce tissue damage.
Changshan ketone exhibits antiproliferative and pro-apoptotic effects across various tumor models. It kills tumor cells by inducing cell cycle blockade, activating mitochondrial pathways, and regulating apoptosis-related proteins. In addition, Changshan ketone can inhibit collagen deposition in the tumor microenvironment, blocking tumor cell invasion and metastasis, demonstrating strong anti-tumor potential.
As an effective pulmonary vasodilator, Changshan ketone can activate voltage-gated potassium channels (Kv channels) and block various calcium channels (voltage-gated, receptor-modulated, and storage-operated Ca2+ channels), thereby reducing pulmonary artery pressure and improving pulmonary hemodynamics. This role provides new approaches for treating pulmonary vascular diseases such as pulmonary hypertension.
Changshanone is a competitive inhibitor of proline-tRNA synthetase, with a Ki value of 18.3 nM, demonstrating high affinity. This enzyme is responsible for linking proline to its corresponding tRNA, which is a key step in protein translation. Changshan ketone exerts anti-fibrotic and antitumor effects by blocking the activity of this enzyme and inhibiting protein synthesis, especially collagen production.
Transforming growth factor β (TGF-β) is an important regulator of fibrosis and inflammation. Changshan ketone can inhibit the activity of TGF-β, block phosphorylation and nuclear translocation of its downstream Smad protein, reduce the expression of collagen and other extracellular matrix proteins, and alleviate tissue fibrosis.
Changshan ketone activates the Kv channel, promoting potassium ion outflow, leading to cell membrane hyperpolarization and reduced cell excitability. At the same time, Changshan ketone blocks voltage-gated, receptor-operated, and storage-operated Ca2+ channels, reducing intracellular calcium ion concentration, relieving vascular smooth muscle constriction, and achieving pulmonary vasodilation effects.
Changshan ketone demonstrates multi-target effects in the antiviral field, involving myeloperoxidase (MPO), herpesvirus proteins UL42, UL54, ICP27, thymidine kinase (TK), viral glycoproteins gD, CCR5 and CXCR4 chemokine receptors, HIV-1 protease (HIV1-PR), and integrase (INT). These targets cover several key steps of viral replication, assembly, and cell invasion, indicating Changshan ketone has broad-spectrum antiviral potential.
The druggability parameters of Changshan ketone indicate that it has good potential for drug development. Its moderate molecular weight and lipid solubility facilitate oral absorption and internal distribution. Its high blood-brain barrier penetration gives it an advantage in treating central nervous system diseases. The negative inhibition of the hERG channel and the low mutagenicity of the Ames test suggest good safety.
Pharmacokinetics, Changshan ketone exhibits good bioavailability and half-life in vivo, maintaining effective plasma concentrations. Its metabolism mainly occurs through hepatic enzyme systems, and the activity and toxicity of these metabolites require further research. Changshan ketone has low potential for drug interactions, making it suitable for combination therapy.
Changshan ketone has demonstrated significant efficacy across various disease models and has broad clinical application potential. Its anti-fibrotic effect provides new therapeutic strategies for chronic diseases such as liver fibrosis, pulmonary fibrosis, and renal fibrosis. The inhibition of the TGF-β signaling pathway gives it potential to alleviate pathological changes in degenerative diseases such as osteoarthritis. The effect of pulmonary vasodilation brings new drug options for the treatment of pulmonary arterial hypertension and other pulmonary vascular diseases.
In addition, Changshan ketone's antimalarial, anti-inflammatory, and anticancer activities provide diverse directions for the treatment of infectious diseases and tumors. Its multi-target and multi-mechanism characteristics help overcome resistance issues of single-target drugs.
Future research should focus on optimizing the pharmacokinetic performance of Changshan ketone, reducing potential toxicity risks, and conducting clinical trials to verify its safety and efficacy. At the same time, by integrating modern drug design technologies, Changshan ketone derivatives and nanoformulations are being developed to enhance their targeting and therapeutic effects.
Changshan ketone, a natural product derived from traditional Chinese medicine, demonstrates broad pharmacological effects and good druggability due to its unique chemical structure and diverse bioactivities. Its potential in anti-fibrosis, anti-inflammation, anti-cancer, and pulmonary vasodilation provides an important example for natural product pharmacology and new drug development. With deeper analysis of its mechanisms of action and advances in drug development technology, Changshan ketone is expected to become an innovative drug for treating various complex diseases. Future research should strengthen clinical translation, promote its transition from the laboratory to clinical applications, and contribute new strength to human health.
