Effect of 2-Isobutyl-4,6-dimethyl-5-hydroxypyrimidine on the Growth of Lewis Lung Carcinoma and Survival of Mice.
Experiments on male C57Bl/6 mice with transplantable Lewis lung epidermoid carcinoma were performed to evaluate the effect of early or delayed administration of compound SNK-411 (2-isobutyl-4,6-dimethyl-5-hydroxypyrimidine) on tumor growth and animal survival. Intraperitoneal injection of SNK-411 in doses of 25 and 50 mg/kg on days 2-8 of tumor growth was followed by significant inhibition of tumor growth (by 1.8 and 2.2 times, respectively, in comparison with the untreated control). Administration of this compound on days 8-15 of tumor development had little effect on tumor growth. SNK-411 in doses of 25 and 50 mg/kg (both dosing regimens) significantly increased survival rate and lifespan of animals with tumors. The drugs for verification of this model (Fluorofur, 400 mg/kg; and doxorubicin hydrochloride, 4 mg/kg) were injected intraperitoneally on days 2-4 and 8-10 of tumor development. Administration of Fluorofur and doxorubicin hydrochloride at the late stage was accompanied by significant inhibition of tumor growth (by 1.6 and 1.4 times, respectively). The increase in the survival rate of animals receiving the cytostatic according to standard dosing regimens was less significant than in experiments with SNK-411.
V. V. Zakusov Research Institute of Pharmacology, Moscow, Russian Federation. kovalenko.larisa@mail.ru.
L P
LP
Kovakenko
V. V. Zakusov Research Institute of Pharmacology, Moscow, Russian Federation.
O S
OS
Kuznetsova
V. V. Zakusov Research Institute of Pharmacology, Moscow, Russian Federation.
A V
AV
Tallerova
V. V. Zakusov Research Institute of Pharmacology, Moscow, Russian Federation.
S V
SV
Nikitin
V. V. Zakusov Research Institute of Pharmacology, Moscow, Russian Federation.
A D
AD
Durnev
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage; D004354:Drug Screening Assays, Antitumor; D007274:Injections, Intraperitoneal; D008297:Male; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011743:Pyrimidines / Q000008:administration & dosage*; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage; D047368:Tumor Burden / Q000187:drug effects
C000612850:2-isobutyl-4,6-dimethyl-5-hydroxypyrimidine; D000970:Antineoplastic Agents; D011743:Pyrimidines; D005641:Tegafur; D004317:Doxorubicin
2-isobutyl-4,6-dimethyl-5-hydroxypyrimidine; Lewis lung carcinoma; antitumor activity; immunotherapy of tumors