Further Study on the Antitumor Activity of a Homo-aza-steroidal Ester of p-N,N-Bis(2-chioroethyl)aminophenylacetic Acid

• Published in: Journal of pharmaceutical sciences 1990-11, Vol.79 (11), p.1040-1040
• Main Author: Catsoulacos, Panayotis
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - pharmacology; Azasteroids; Biological and medical sciences; Female; General aspects; Leukemia P388 - drug therapy; Male; Medical sciences; Mice; Nitrogen Mustard Compounds - pharmacology; Pharmacology. Drug treatments; Receptors, Steroid - drug effects; Receptors, Steroid - metabolism
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600791121

To the Editor: To increase the selectivity of the antitumor action of alkylating agents, new biological platforms that enable delivery of the alkylating moities to specific target sites have been suggested. These biological platforms have various chemical structures and biological properties. On the other hand, for modified steroidal esters, we suggest that in addition to an easily cleaved ester bond (a basic requirement for antitumor activity), that the steroidal lactam moiety is required for activity in leukemia L1210 and P388.1 One such promising compound, 3β-hydroxy-13α-amino-13,17-seco-5α- androstan-17-oic-13,17-lactam-p-N,N-bis(2-chloro-ethyl)aminophenylacetate2 (ASE; NSC 620482) has good activity in L1210 and P388 leukemias,3 T8-Guerin tumors, Theagenion-Bahner angiosarcoma,4 B16 melanosarcoma, Colon 26 tumor, CD8F mammary tumor,5 CX-1 xenograft, LX-1 xenograft, MXT-1 hormonal-dependent transplantable mammary adenocarcinoma, and Colon 38 tumor.6 This compound (ASE) was submitted to the National Cancer Institute for further testing in P388 leukemia, and the results are reported in Table I. The compound ASE is active in P388 leukemia following a single injection on day 1 by the ip route of administration (T/C > 125%). It is also one of the more active compounds in this series of modified steroidal alkylating agents. The drug ASE has confirmed activity in 10 experimental animal tumors, including two human xenografts. Since the antineoplastic activity of this drug is superior to older or unmodified steroidal alkylating agents,7 it is an attractive candidate for clinical trial.