Melphalan


Melphalan, sold under the trade name Alkeran among others, is a chemotherapy medication used to treat multiple myeloma, ovarian cancer, melanoma, and amyloidosis. It is used by mouth or by injection into a vein.
Common side effects include nausea and bone marrow suppression. Other severe side effects may include anaphylaxis and the development of other cancers. Use during pregnancy may result in harm to the baby. Melphalan belongs to the class of nitrogen mustard alkylating agents. It works by interfering with the creation of DNA and RNA.
Melphalan was approved for medical use in the United States in 1964. It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system. It is available as a generic medication. In the United Kingdom it costs the NHS £137 per 50 mg vial. In the United States the cost of this amount is.

Medical uses

It is used to treat multiple myeloma, ovarian cancer, AL amyloidosis, and occasionally malignant melanoma.
The agent was first investigated as a possible drug for use in melanoma, it was not found to be effective.
In 2016, it was approved in the U.S. for:
Melphalan is currently being used to treat ocular retinoblastoma, a pediatric solid tumor. This is accomplished via transarterial catheter based slow pulsed infusion into the ophthalmic artery.

Side effects

Common side effects include:
Less common side effects include:
Melphalan chemically alters the DNA nucleotide guanine through alkylation, and causes linkages between strands of DNA. This chemical alteration inhibits DNA synthesis and RNA synthesis, functions necessary for cells to survive. These changes cause cytotoxicity in both dividing and non-dividing tumor cells.

Synthesis

Another amino acid-like drug is the antineoplastic agent melphalan. Tumor cells spend less time in resting phases than normal cells so at any given time, they are more likely to be metabolically active than most normal host cells. The rationale behind incorporating an alkylating function in a molecule resembling a primary cellular metabolite was to get a greater safety margin by fooling tumor cells into taking up the toxin preferentially.
4-Nitro-L-phenylalanine was converted to its phthalimide by heating with phthalic anhydride, and this was converted to its ethyl ester. Catalytic hydrogenation produced the corresponding aniline. Heating in acid with oxirane, followed by treatment with phosphorus oxychloride provided the bischloride, and removal of the protecting groups by heating in hydrochloric acid gave melphalan.