Trade names Alkeran MedlinePlus a682220 Molar mass 305.2 g/mol | AHFS/Drugs.com Monograph ATC code L01AA03 (WHO) CAS ID 148-82-3 | |
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Legal status In general: ℞ (Prescription only) | ||
Melphalan meaning
Melphalan (trade name Alkeran, in former USSR also known as Sarcolysin) is a chemotherapy drug belonging to the class of nitrogen mustard alkylating agents.
Contents
An alkylating agent adds an alkyl group (CnH2n+1) to DNA. It attaches the alkyl group to the guanine base of DNA, at the number 7 nitrogen atom of the imidazole ring.
Otherwise known as L-phenylalanine mustard, or L-PAM, melphalan is a phenylalanine derivative of mechlorethamine.
Melphalan
Mechanism of action
Melphalan chemically alters through alkylation of the DNA nucleotide guanine, 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.
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.
On March 15, 2016 it was approved by the U.S. FDA under the trade name Evomela 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.
Administration
Oral or intravenous; dosing varies by purpose and route of administration as well as patient weight.
Melphalan Prescribing Information: Alkeran
Melphalan Patient Information: MedlinePlus
Melphalan Material Safety Data Sheet (MSDS): Sequoia Research Products
Side effects
Common side effects include:
Less common side effects include:
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.
p-Nitrophenyl-alanine (1) was converted to its phthalimide by heating with phthalic anhydride, and this was converted to its ethyl ester (2). 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 (3).