Melphalan
[CAS# 148-82-3]

Identification

• Classification: API >> Antineoplastic agents >> Alkylating agent
• Name: Melphalan
• Synonyms: 4-[Bis(2-chloroethyl)amino]-L-phenylalanine; 2-Amino-3-[4-[bis(2-chloroethyl)amino]phenyl]propanoic acid; L-Phenylalanine mustard; L-PAM
• Molecular Formula: C₁₃H₁₈Cl₂N₂O₂
• Molecular Weight: 305.20
• CAS Registry Number: 148-82-3
• EC Number: 205-726-3
• SMILES: C1=CC(=CC=C1C[C@@H](C(=O)O)N)N(CCCl)CCCl

Properties

• Melting point: 177 ºC
• Water solubility: <0.1 g/100 mL at 22 ºC

Safety Data

• Hazard Symbols: GHS06;GHS08 Danger
• Hazard Statements: H300-H310-H330-H340-H350-H361
• Precautionary Statements: P203-P260-P262-P264-P270-P271-P280-P284-P301+P316-P302+P352-P304+P340-P316-P318-P320-P321-P330-P361+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	2	H300
Reproductive toxicity	Repr.	2	H361
Acute toxicity	Acute Tox.	2	H310
Carcinogenicity	Carc.	1B	H350
Acute toxicity	Acute Tox.	1	H330
Germ cell mutagenicity	Muta.	1B	H340
Carcinogenicity	Carc.	1A	H350
Reproductive toxicity	Repr.	1A	H360
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Acute toxicity	Acute Tox.	1	H300
Serious eye damage	Eye Dam.	1	H318
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Skin sensitization	Skin Sens.	1	H317

• Transport Information: UN 2811

Discovory and Applicatios

Melphalan, also known as L-phenylalanine mustard, was first synthesized in the early 1950s by researchers working to develop new cancer treatments. It is an alkylating agent, derived from nitrogen mustard, which was originally used as a chemical warfare agent. Recognizing the potential of alkylating agents to disrupt DNA replication in rapidly dividing cells, scientists adapted nitrogen mustard compounds for therapeutic use. Melphalan was designed to target and destroy cancer cells, and its efficacy was soon demonstrated in clinical settings. It was one of the earliest chemotherapy drugs to be used in the treatment of multiple myeloma and ovarian cancer.

One of the primary applications of melphalan is in the treatment of multiple myeloma, a type of blood cancer that affects plasma cells in the bone marrow. Melphalan works by binding to DNA and cross-linking strands, thereby preventing cancer cells from dividing and growing. This makes it effective in reducing the proliferation of myeloma cells and helping to manage symptoms and progression of the disease.

Melphalan is also crucial in the preparation for bone marrow transplantation. High-dose melphalan is administered as part of the conditioning regimen before autologous stem cell transplantation for patients with multiple myeloma. This high-dose therapy helps to eradicate residual cancer cells in the bone marrow, increasing the chances of successful transplantation and long-term remission.

In addition to multiple myeloma, melphalan has been used to treat ovarian cancer. Its mechanism of action is similar, targeting rapidly dividing cancer cells. While newer treatments have emerged, melphalan remains an option, particularly in cases where other therapies have failed or are not suitable.

Melphalan continues to be a subject of research for its potential applications in other types of cancers and in combination with newer therapeutic agents. Researchers are investigating its use in combination with immunotherapies and targeted therapies to enhance efficacy and reduce side effects.

In some cases, melphalan is used in palliative care to manage symptoms and improve the quality of life for patients with advanced cancer. By controlling tumor growth, it can help alleviate pain and other symptoms associated with cancer..

Efforts are ongoing to develop new formulations of melphalan that improve its delivery and reduce toxicity. Liposomal formulations, for example, can enhance the drug's bioavailability and target delivery to cancer cells more effectively, potentially reducing side effects and improving patient outcomes.

References

1991. The relationship between nuclear glutathione levels and resistance to melphalan in human ovarian tumour cells. Biochemical Pharmacology, 41(4).
DOI: 10.1016/0006-2952(91)90642-i

1991. Monoclonal antibody-purged autologous bone marrow transplantation therapy for multiple myeloma. Blood, 77(4).
DOI: 10.1182/blood.v77.4.712.712

1990. The effect of hyperthermia in combination with melphalan on drug-sensitive and drug-resistant CHO cells in vitro. British Journal of Cancer, 62(2).
DOI: 10.1038/bjc.1990.257