Phenylalanine mustard

The drug melphalan (phenylalanine mustard, 11.33, R = R = Cl) is another good example of a nitrogen mustard that undergoes hydrolytic dechlorination. Melphalan administered to cancer patients gives rise to the monohydroxy (11.33, R = Cl, R = OH) and dihydroxy metabolites (11.33, R = R = OH), which were detected in the plasma with a combined AUC (area-under-the-curve) amounting to 29% of the AUC of the drug [68],... 

Other Names Alkeran , L-Sarcolysine, L-PAM, L-Phenylalanine Mustard, Compound CB 3025, Compound NSC-8806. 

Drags which have structures similar to that of endogenous nutrients may be taken up by a specialized transport system (carrier-mediated transport, receptor-mediated transcytosis) existing in the brain endothelium for nutrients. For example, drags having a molecular structure similar to a large neutral amino acid may cross the BBB via the neutral amino acid carrier such drags include melphalan (phenylalanine mustard), L-dopa, a-methyldopa, and p-chlorophenylalanine. 

As discussed above, certain nutrients are taken up into the brain by carrier-mediated systems. If a dmg possesses a molecular structure similar to that of a nutrient which is a substrate for carrier-mediated transport (Table 13.1), the pseudo-nutrient dmg may be transported across the BBB by the appropriate carrier-mediated system. For example, the dmg L-dopa crosses the BBB via the neutral amino acid carrier system. Other neutral amino acid dmgs that are transported through the BBB on this transport system are a-methyldopa, a-methylparatyrosine, and phenylalanine mustard. 

The methods are described for the preparation of DNA modified with the anticancer drug melphalan (phenylalanine mustard), and for the production of antibodies that specifically recognize the drug modified sites. 

A tetrahydrocannabinol-BSA conjugate has been made by reaction with lO-iodotetrahydrocannabinol-9-isocyanate. L-Phenylalanine mustard is another example of a reactive hapten. ... 

Melphalan (L-phenylalanine mustard) is an alkylating agent that has been used to treat a wide variety of solid malignancies, including cancers of the breast and ovary, and multiple myeloma. Intravenous melphalan has been used to treat rhabdomyosarcoma, lymphomas, multiple myeloma, and neuroblastoma (1). 

Figure 4, Fast atom bombardment mass spectrum of the diglutathtone conjugate of phenylalanine mustard (jM).

Jendryczko A and Drozdz M (1985). Action of phenylalanine mustard on collagen in vivo. Biomed Biochim Acta, 44, 497-501. 

Drug Treatments. Cis-Diamminedichloroplatinum(II) (NSC 119875) and trans-Diamminedichloroplatinum(II) (NSC 131558) were obtained from the National Cancer Institute and were always constituted in isotonic, aqueous solution Just prior to use. L-phenylalanine mustard (NSC 8806) was dissolved in 0.1 N HCl and stored frozen. 

Somfai-Relle, S., Suzukake, K., Vistica, B. P., and Vistica, D. T., Reduction in cellular glutathione by buthionine sulphoximine and sensitization of murine tumour cells resistant to L-phenylalanine mustard. Biochem. Pharmacol. 33, 485 (1984). 

Stout SA and Riley CM, The hydrolysis of L-phenylalanine mustard (melphalan), Int. f. Pharm., 24,193-208 (1985). NB Estimated from hydrolytic rate constants in file pH range 1-13. Taken from Stout SA, Chemical stability and in vitro cytotoxicity of melphalan, Ph.D. Thesis, University of Florida, 1987,36-42. 

Quantitation by Gas Chromatography-Chemical Ionization Mass Spectrometry of Phenylalanine Mustard in Plasma of Patients Cancer Res. 40(7) 2268-2272 (1980) ... 

Carbamoyl chloride 211 of di(2-chloroethyl)amine 210, a useful intermediate in the preparation of nitrogen mustards and t-phenylalanine mustards as antitumor agents [127], was prepared in 85% yield using triphosgene and pyridine as acid scavenger at temperatures below 20 °C [128, 129]. 

Synonymo 4-1Bis(2-chloroethyl)amino]-L-phenylalanine L-phenylalanine mustard alanine nitrogen mustard, PAM phenylalanine nitrogen mustard Trade names Alkeran, Medphalan, Merphalan, Sarcolysine... 

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