A novel antitumor compound, N-[4-(5-bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2-nitrobenzoyl )
urea (HO-221) was evaluated for its antitumor activity in experimental
tumor models.
HO-221 preparation was given orally to
tumor-bearing animals. The compound exhibited significant effects against various
tumors such as P388 and L1210
leukemias; M5076
reticulum-cell sarcoma; colon 38
carcinoma; human xenografts MX-1, LX-1, GA-1, and Co-1;
Lewis lung carcinoma;
sarcoma 180; and Walker 256
carcinosarcoma and was especially effective against solid
tumors. However, its effect on murine
B16 melanoma was moderate. Intermittent administration of
HO-221 produced better results. The effects of
HO-221 on human
tumor xenografts were compared with those of other
antitumor agents.
HO-221 showed activity against LX-1 lung and Co-1 gastrointestinal
tumor and was also effective against advanced-stage
L1210 leukemia and
Lewis lung carcinoma. Furthermore, the effect of
HO-221 on
drug-resistant
tumors was examined using murine
leukemias L1210 and P388. It showed no cross-resistance with the known
antitumor agents Adriamycin (ADM),
daunomycin (DM),
vincristine (VCR),
mitomycin C (MMC),
cisplatin (CDDP),
5-fluorouracil (5-FU),
cytosine arabinoside (
Ara-C),
methotrexate (MTX),
cyclophosphamide (CPA), or
carboquone (CQ), and collateral sensitivity to
HO-221 was found in MMC-, CDDP-, and CPA-resistant sublines.
HO-221 exhibits significant reproducible, broad-spectrum antitumor activity against experimental
tumors as well as human
neoplasms.