The future of alkylating agents

A number of compounds bind by hydrogen bonding to the minor groove of DNA and then form cross-links. They exhibit sequence selectivity as to which nucleotide sequences they bind. They may, thus, be useful in targeting certain tumours selectively. Other approaches to selective tumour kill involve the use of:

♦ ADEPT (Antibody-Directed Enzyme Pro-drug Targeting)—a tumour-specific antibody linked to an enzyme that is not normally expressed in human cells is given to the patient, followed by a pro-drug that is activated by this enzyme to a cytotoxic agent.

♦ GDEPT (Gene-Directed Enzyme Pro-drug Targeting)—similar to ADEPT but tumour is made to express the enzyme by gene therapy techniques.

Many of the pro-drugs currently being used are alkylating agents.

^ CCNU: 1-(2-chloroethyl-3-cyclo-hexyl-1)- nitrosourea = lomustine ^ BCNU: 1,3-bis(2-chloroethyl)-1-nitrosourea = carmustine.

0 0

Post a comment