Immunomodulating and antiviral activities of the imidazoquinoline S-28463.
Recently, a new class of immunomodulating agents, represented by the molecules imiquimod and R-842, has demonstrated potent antiviral and antitumor activities in animal models. In this study, another representative of this class, S-28463 (4-amino-2-ethoxymethyl-alpha,alpha-dimethyl-1H-imidazo[4,5-c]quinoline- 1- ethanol) was evaluated for its immunomodulating and antiviral activities. S-28463 induced IFN and other cytokines in vivo in mice, rats, monkeys and in vitro in human peripheral blood mononuclear cell cultures. S-28463 showed potent antiviral activity against herpes simplex virus-challenged guinea pigs when given subcutaneously, dermally, or intravaginally 24 h before infection. Antiviral activity in guinea pigs correlated with the induction of serum 2',5'-oligoadenylate synthetase activity. Thus, S-28463, like the other imidazoquinolines, demonstrates potent antiviral and immunomodulating effects in a number of models.
Tomai
M A
MA
Department of Pharmacology, 3M Pharmaceuticals, St. Paul, MN 55144, USA.
Gibson
S J
SJ
Imbertson
L M
LM
Miller
R L
RL
Myhre
P E
PE
Reiter
M J
MJ
Wagner
T L
TL
Tamulinas
C B
CB
Beaurline
J M
JM
Gerster
J F
JF
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006168:Guinea Pigs; D006561:Herpes Simplex / Q000517:prevention & control; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D007369:Interferon Inducers / Q000494:pharmacology; D016898:Interferon-alpha / Q000096:biosynthesis; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D000998:Antiviral Agents; D016207:Cytokines; D007369:Interferon Inducers; D016898:Interferon-alpha; C099445:S 28463; D014409:Tumor Necrosis Factor-alpha; D015088:2',5'-Oligoadenylate Synthetase