Chemotherapeutic characterization in mice of 2-amino-9-beta-D-ribofuranosylpurine-6-sulfinamide (sulfinosine), a novel purine nucleoside with unique antitumor properties.
In preclinical investigations performed in mice, 2-amino-9-beta-D-ribofuranosyl purine-6-sulfinamide (sulfinosine), a novel derivative of 6-thioguanosine (6TGR), was active against six solid tumors and four strains of experimental leukemia. Sulfinosine penetrated the central nervous system more readily than did 6TGR and, when given repeatedly, was much more effective in the treatment of L1210 leukemia, being curative for some mice. Other findings of major interest to us were the different dosing characteristics of sulfinosine and 6TGR, the divergent efficiencies of the two drugs in generating cellular resistance, and the activity of sulfinosine against experimental leukemias refractory to 6TGR and other experimental or clinically used chemotherapeutic agents. The chemotherapeutic characterization of sulfinosine that evolved from these studies suggests that this agent may have unique properties that deserve clinical consideration. Both the dosing characteristics of the drug and its pronounced activity against thiopurine-resistant experimental leukemia favor the possibility that sulfinosine could be used to advantage in the treatment of human leukemia unresponsive to 6-mercaptopurine or 6-thioguanine.
Avery
T L
TL
ICN Nucleic Acid Research Institute, Costa Mesa, California 92626.
Finch
R A
RA
Vasquez
K M
KM
Radparvar
S
S
Hanna
N B
NB
Revankar
G R
GR
Robins
R K
RK
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D006151:Guanosine / Q000031:analogs & derivatives / Q000627:therapeutic use; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D011684:Purine Nucleosides / Q000627:therapeutic use*; D013872:Thionucleosides / Q000627:therapeutic use
D000970:Antineoplastic Agents; D011684:Purine Nucleosides; D013872:Thionucleosides; D006151:Guanosine; C063871:sulfinosine; C005783:6-thioguanosine