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Synonym name: Irinotecan Related Compound E
Catalogue No.: BP0100
Cas No.: 78287-27-1
Formula: C22H20N2O4
Mol Weight: 376.412
Botanical Source:
Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.
For Reference Standard and R&D, Not for Human Use Directly.
Inquire for bulk scale.
HPLC of 7-Ethylcamptothecin
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
86.1300
2.2500
1.7800
High
No
No
No
No
No
Negative
7-Ethylcamptothecin (CAS No.: 78287-27-1) is a natural product derivative with significant antitumor activity, belonging to the pyranp-inazine and quinoline class compounds. As a structural modification product of camptothecin (CPT), 7-ethylcamptothecin has attracted significant attention in the field of anticancer drug development. It exhibits superior pharmacodynamic properties compared to camptothecin in vivo, especially showing stronger activity in tumor cell growth inhibition, longer retention time in the intestines, and higher bioavailability. In addition, 7-ethylcamptothecin is a key intermediate in the synthesis of 7-ethyl-10-hydroxycamptothecin (SN-38), which is the active metabolite of the widely used anticancer drug Irinotecan.
In recent years, besides its potential in tumor treatment, 7-ethylcamptothecin has also shown new application prospects in research related to diseases such as pulmonary hypertension (PH). By regulating multiple molecular targets—including DNA topoisomerase I (TOP1), hypoxia-inducible factor 1α (HIF1A), histone deacetylase 6 (HDAC6), endothelin receptor B (EDNRB), and proline hydroxylase (EGLN1)—7-ethylcamptothecin is expected to exert multi-target synergistic regulatory effects and expand its clinical indications.
This paper will systematically review the chemical structure and physicochemical properties of 7-ethylcamptothecin, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation and pharmacokinetic characteristics, and explore its clinical application prospects and future development directions, aiming to provide theoretical basis and research reference for the pharmacology of natural products and the development of antitumor drugs.
7-Ethylcamptothecin is a complex pyranidine inazine quineline alkaloid with a molecular formula C20H21N2O4 and a molecular weight of 376.41. Structurally, 7-ethylcamptothecin introduces an ethyl substituent at the 7th position based on camptothecin, a structural modification that significantly affects its pharmacological activity and pharmacokinetic properties. Its core structure includes a polycyclic system fused with pyranan rings and inazine rings, featuring a typical indoleline alkaloid backbone and containing polar functional groups such as hydroxyl and carboxyl groups.
In terms of physicochemical properties, the LogP of 7-ethylcamptothecin is 2.25, indicating moderate lipid solubility, which is beneficial for cell membrane penetration and distribution in vivo. Its topological pole surface area (TPSA) is 86.13 Ų, and it has 6 hydrogen bond receptors, both meeting the drug similarity rules for oral small molecule drugs (such as the Lipinski rule), suggesting good oral bioavailability potential. The high permeability of the blood-brain barrier suggests it may affect the central nervous system, so safety should be considered in clinical practice.
Toxicological evaluation showed that 7-ethylcamptothecin carries low hepatotoxicity risk, shows no cardiotoxicity, does not show hERG channel inhibitory effects, and the Ames mutagenic test is negative. Overall, its safety is relatively ideal, meeting the requirements for further clinical development.
7-Ethylcamptothecin originally originated from the structural modification of camptothecine, a natural product of camptotheca acuminata, a traditional Chinese medicinal herb. Gerisa is a member of the Bignoniaceae family, mainly distributed in southern China and Southeast Asia. Its dried bark and root bark are rich in camptothecin and its derivatives. The extraction of camptothecin is usually done using organic solvent extraction combined with liquid chromatography separation and purification technology, with mature extraction processes and stable yields.
7-Ethylcamptothecin is a semi-synthetic derivative of camptothecin and is usually obtained through chemical synthesis routes. This synthesis process uses camptothecin as the starting material and undergoes a 7-position ethylation reaction to achieve structural modification. Key steps in the synthesis process include selective protection and deprotection, nucleophilic substitution reactions, and purification separation, ensuring high product purity and structural integrity.
In recent years, with the development of synthetic biology and enzyme catalysis technologies, some studies have attempted to improve the yield and environmental friendliness of 7-ethylcamptothecin through microbial fermentation and enzyme-catalyzed synthesis strategies. Additionally, constructing a derivatives library based on camptothecin also makes it possible to find analogs with more active and superior pharmacokinetic properties.
The pharmacological activity of 7-ethylcamptothecin is mainly reflected in its antitumor effects. Compared with the parent compound camptothecin, 7-ethylcamptothecin exhibits stronger growth inhibition in various tumor cell lines. Its anti-tumor activity covers solid tumors such as lung cancer, colorectal cancer, breast cancer, and ovarian cancer, and has demonstrated good anti-tumor effects in vivo animal models.
In vivo pharmacodynamic studies have shown that 7-ethylcamptothecin has a longer residence time in the intestine, longer blood concentration maintenance, significantly improved bioavailability, reduced dosing frequency, and dose-dependent toxic side effects. Its distribution advantage in the tumor microenvironment enhances selective killing of tumor cells.
In addition to antitumor effects, 7-ethylcamptothecin also shows potential therapeutic value in research on non-tumor diseases such as pulmonary hypertension. Pulmonary hypertension is a fatal disease characterized by elevated pulmonary artery pressure. 7-Ethylcamptothecin shows potential for alleviating pulmonary hypertension symptoms by regulating key molecular targets, inhibiting vascular remodeling and inflammatory responses.
The main mechanism of action of 7-ethylcamptothecin is to inhibit DNA topoisomerase I (TOP1) activity, blocking DNA replication and transcription processes, thereby inducing tumor cell apoptosis. TOP1 is a key enzyme for maintaining the DNA superhelix. 7-Ethylcamptothecin binds to the TOP1-DNA complex, stabilizing the complex, leading to DNA strand breakage and accumulation, ultimately triggering cell death.
Additionally, 7-ethylcamptothecin has therapeutic potential for pulmonary hypertension, involving multi-target regulation:
HIF1A (hypoxia-inducible factor 1α): 7-Ethylcamptothecin can inhibit the expression and activity of HIF1A, alleviating abnormal vascular proliferation and metabolic reprogramming under hypoxic conditions.
HDAC6 (histone deacetylase 6): By regulating HDAC6 activity, 7-ethylcamptothecin affects cytoskeletal remodeling and inflammatory responses, helping to alleviate abnormal proliferation of pulmonary vascular smooth muscle cells.
EDNRB (endothelin receptor B): regulates vasoconstriction and dilation. 7-Ethylcamptothecin improves pulmonary artery pressure by affecting the EDNRB signaling pathway.
EGLN1 (proline hydroxylase): As a regulatory factor of HIF1A, EGLN1 activity is indirectly regulated by 7-ethylcamptothecin, further affecting hypoxia response.
These multi-target mechanisms not only enhance the therapeutic efficacy of 7-ethylcamptothecin but also provide a theoretical basis for its application in various diseases.
The druggability parameters of 7-ethylcamptothecin indicate that it has promising potential for drug development. Molecular weight 376.41, LogP 2.25, and TPSA 86.13 fall within the ideal range in drug design, indicating good membrane permeability and oral absorption capacity. It has 6 hydrogen bond receptors, which facilitates stable binding with biological macromolecules.
The high permeability of the blood-brain barrier suggests it may penetrate the central nervous system, so attention should be paid to potential CNS toxicity and side effects. Toxicological assessment showed low risk of hepatotoxicity, no cardiotoxicity or hERG channel suppression, negative Ames test, and generally good safety.
Pharmacokinetic studies have shown that 7-ethylcamptothecin has a long half-life and high bioavailability in the body, with extended intestinal residence time, which is beneficial for oral administration. Its metabolic pathways are mainly transformed through hepatic enzyme systems, and the activity and toxicity of these metabolites require further in-depth study.
As an important derivative of camptothecin antitumor drugs, 7-ethylcamptothecin has broad clinical application prospects due to its excellent antitumor activity and good safety profile. It shows potential advantages in treating various solid tumors such as lung cancer and colorectal cancer, and is especially suitable for oral anticancer drug development to improve patient compliance.
In addition, the multi-target mechanism of 7-ethylcamptothecin in non-tumor diseases such as pulmonary hypertension offers new possibilities for expanding its indications. In the future, precision medicine strategies can be combined to design personalized treatments targeting specific molecular targets.
Future research directions include:
Optimizing synthesis processes to improve yield and purity while reducing production costs.
In-depth analysis of its pharmacokinetics and metabolic mechanisms to clarify the active metabolites and toxicity risks.
Combining nanotechnology with drug delivery systems to improve targeting and therapeutic efficacy.
Preclinical and clinical trials are conducted to verify its safety and effectiveness.
Explore combination drug strategies to enhance anti-tumor efficacy and overcome drug resistance.
As a structural modification product of camptothecin, 7-ethylcamptothecin has become an important research subject in the field of natural product pharmacology due to its excellent antitumor activity and good pharmacokinetic properties. Its multi-target mechanism not only broadens the therapeutic scope of anticancer drugs but also provides new ideas for treating diseases such as pulmonary hypertension. With continuous advances in synthetic technology and drug delivery systems, 7-ethylcamptothecin is expected to play a greater role in clinical practice, becoming a new generation of highly efficient and safe anti-tumor and pulmonary hypertension treatment drugs. In the future, systematic pharmacological research and clinical validation will be key to driving its translational application.
Shenshuai
Wenjing
Hedandan
