Lapatinib ditosylate monohydrate
[CAS# 388082-78-8]

Identification

• Classification: Organic raw materials >> Amino compound >> Sulfonic acid amino compound
• Name: Lapatinib ditosylate monohydrate
• Synonyms: N-(3-Chloro-4-((3-fluorophenyl)methoxy)phenyl)-6-(5-(((2-(methylsulfonyl)ethyl)amino)methyl)-2-furanyl)-4-quinazolinamine bis(4-methylbenzenesulfonate) monohydrate
• Molecular Formula: C₂₉H₂₆ClFN₄O₄S.2(C₇H₈O₃S).H₂O
• Molecular Weight: 943.47
• CAS Registry Number: 388082-78-8
• EC Number: 642-915-3
• SMILES: CC1=CC=C(C=C1)S(=O)(=O)O.CC1=CC=C(C=C1)S(=O)(=O)O.CS(=O)(=O)CCNCC1=CC=C(O1)C2=CC3=C(C=C2)N=CN=C3NC4=CC(=C(C=C4)OCC5=CC(=CC=C5)F)Cl.O

Safety Data

• Hazard Symbols: GHS08 Danger
• Risk Statements: H361-H362-H372-H413
• Safety Statements: P203-P260-P263-P264-P270-P273-P280-P318-P319-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Chronic hazardous to the aquatic environment	Aquatic Chronic	4	H413
Reproductive toxicity	Repr.	1B	H360
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Reproductive toxicity	Lact.	-	H362

Discovery and Applications

Lapatinib ditosylate monohydrate is a pharmaceutical compound primarily used in the treatment of certain types of breast cancer. It is a potent, oral, small-molecule inhibitor of both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). These receptors are overexpressed in some cancer cells and play a critical role in cancer cell proliferation, survival, and metastasis. Lapatinib works by targeting and inhibiting these receptors, thereby disrupting the signaling pathways that lead to tumor growth and progression.

The discovery of lapatinib was driven by the need to develop targeted therapies for cancers that overexpress HER2. HER2-positive breast cancer is a particularly aggressive form of cancer, and while the monoclonal antibody trastuzumab (Herceptin) has been a cornerstone of treatment, many patients develop resistance to trastuzumab over time. Lapatinib was developed as an alternative treatment for these cases, with the goal of providing a second-line therapy for patients with advanced or metastatic HER2-positive breast cancer who no longer respond to trastuzumab or other conventional chemotherapy.

Lapatinib's mechanism of action is based on its ability to inhibit both EGFR and HER2 tyrosine kinase activity. These receptors are members of the ErbB family of receptor tyrosine kinases, which are involved in the regulation of various cellular processes, including growth, survival, and differentiation. By blocking the activation of these receptors, lapatinib prevents the downstream signaling pathways that would otherwise promote cancer cell division and survival. This inhibition reduces the growth and spread of tumors, leading to a decrease in cancer progression.

The clinical use of lapatinib is primarily in combination with other drugs, particularly in the treatment of HER2-positive breast cancer. It is commonly used in combination with capecitabine or letrozole for patients who have not responded to other therapies, including trastuzumab. Lapatinib is particularly valuable in cases of advanced or metastatic breast cancer, where it has shown significant efficacy in slowing disease progression and improving patient outcomes. It is also used in combination with chemotherapy for the treatment of HER2-positive breast cancer in the metastatic setting.

In addition to breast cancer, lapatinib has been investigated for its potential use in the treatment of other cancers, including non-small cell lung cancer (NSCLC) and head and neck cancers, where HER2 and EGFR overexpression can also play a significant role in tumor development. However, its primary approved use remains in breast cancer therapy.

Despite its efficacy, lapatinib is not without side effects. The most common adverse effects include diarrhea, nausea, fatigue, and skin rash. More serious side effects may include liver toxicity and heart problems, such as cardiac arrhythmias or a reduction in heart function. As with other cancer therapies, the risk of side effects necessitates close monitoring during treatment, and the drug may need to be discontinued or adjusted based on the severity of these effects.

Lapatinib's development represents an important step in the field of targeted cancer therapy. It offers a more specific treatment option for patients with HER2-positive breast cancer, particularly those who have developed resistance to other therapies. By focusing on the molecular mechanisms driving cancer cell growth, lapatinib helps to target cancer cells more precisely, offering the potential for improved outcomes with fewer side effects compared to traditional chemotherapy.

In conclusion, lapatinib ditosylate monohydrate is a critical drug in the treatment of HER2-positive breast cancer, particularly for patients who have not responded to other treatments. Its ability to inhibit EGFR and HER2 receptors plays a vital role in slowing tumor growth and improving survival rates. While it can cause side effects, its targeted action offers a promising alternative to conventional chemotherapy, especially for advanced stages of cancer. The ongoing research into lapatinib's use in other cancers further highlights its potential as an effective cancer treatment.

References

2008. HER-2 Gene Amplification, HER-2 and Epidermal Growth Factor Receptor mRNA and Protein Expression, and Lapatinib Efficacy in Women with Metastatic Breast Cancer. Clinical Cancer Research, 14(23).
DOI: 10.1158/1078-0432.ccr-08-1056

2008. Evaluation of Lapatinib and Topotecan Combination Therapy: Tissue Culture, Murine Xenograft, and Phase I Clinical Trial Data. Clinical Cancer Research, 14(23).
DOI: 10.1158/1078-0432.ccr-08-0415

2024. Lapatinib-loaded reductive-responsive hyaluronic acid-cholesterol nanoparticles for inhibiting metastasis of uveal melanoma. International Journal of Biological Macromolecules, 285.
DOI: 10.1016/j.ijbiomac.2024.137028