L-Phenylalanine mustard

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

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). 

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. 

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

Therapeutic Function Cancer chemotherapy Chemical Name 4-[bis(2-chloroethyl)amino]-L-phenylalanine Common Name Alanine nitrogen mustard L-sarcolysine Structural Formula... 

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. 

AT-290 p-N-BIS(2-CHLOROETHYL)AMINO-l-PHENYLALANINE l-3-(p-(BIS(2-CHLOROETHYL)-AMINO)PHENYL)ALANINE 3-(p-(p-(BIS(2-CHIT)ROETHYL)AMINO)PHENYL))-l-ALANINE 4-(BIS(2-CHLOROETHYL)AMINO)-l-PHENYLALANINE CB 3025 p-N-DI(CHLOROETHYL)AMINOPHENYL-ALANINE p-DI-(2-CHLOROETHYL)AMINO-l-PHENYLALANINE 3-p-(DI(2-CHLOROETHYL)-AMINO)-PHENYL-l-ALANINE MELPHALAN NCI-C04853 NSC-8806 1-PAM PHENYLALANINE NITROGEN MUSTARD RCRA WASTE NUMBER U150... 

The LAT system has been used for the transport of various compounds to the brain. Variations in the cerebellum to plasma ratio at late times in 6-[18F]fluoro-L-DOPA studies are consistent with competitive binding of large neutral amino acids (LNAAs) for the LAT at the BBB (117). In addition, it was shown that oral administration of phenylalanine inhibited the uptake of an artificial amino acid [(1 lC)-aminocyclohexanecarboxylate] in human brain (118). Melphalan, a nitrogen mustard derivative of the neutral amino acid L-phenylalanine, was transported to the brain via the LAT system at the rat BBB. In addition, it was shown that melphalan competed with phenylalanine for the LAT system (119). 

Bis (2-chloroethyl) amino]-L-phenylalanine L-Mustard L-Sarcolysin USP BP Alkeran (Burroughs Wellcome) ... 

L-Phenylalanine L-Proline L-Serine L-Threonine L-Tryptophan L-Tyrosine L-Valine ing. care agent, cosmetics Zinc chloride inhalant inhibitor Mustard oil... 

According to a hypothesis launched by Larionov et al in the 1960s, some new nitrogen mustard derivatives were developed. They contain metabolites and heterocyclic structures as carriers of the cytotoxic chloroethylamine groups. By this way the synthesis of aliylating metabolites started melphalan (sarcolysine) as L- or DL-phenylalanine derivative prospidine with a tricyclic piperazine moiety and chlorambucil as butyric acid derivative. It was proven that each alkylating metabolite has its own spectrum of selective antitumor activity. 

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