5882

PM00104 has demonstrated antiproliferative in vitro activity against a broad spectrum of human solid and non-solid tumor types. Regarding solid tumors, PM00104 exhibited in vitro antitumor activity (i.e., IC50 ≤ 10-8 M) against representative cell lines of bladder, gastric, kidney, melanoma, pancreas, prostate, sarcoma, and thyroid; similar activities were noted against leukemia and lymphoma as representatives of non-solid tumors. PM00104 also demonstrated in vitro antitumor activity, although to a lesser extent (i.e., IC50 ranging from 10-7 to 10-6 M), in representative cell lines of breast, colon, lung, prostate (DU-145), sarcoma (SK-LMS-1 and SW-684), and lymphoma (U937). In vitro activity (i.e., 10-6 to 10-5 M) was not seen, however, in a representative ovarian cell line (SK-OV-3). In vivo tumor profiling of compound PM00104 was accomplished by using a panel of six human tumor types, i.e., breast, colon, gastric, ovarian, prostate, and renal. The resulting tumor susceptibility was analyzed in xenografts grown in athymic mice when PM00104 was administered as single intravenous bolus (SIVB) injections. PM00104 demonstrated statistically significant antitumor activity against breast, gastric, and renal malignancies [i.e., lowest ratio deltaT/deltaC = -65% (on Day 9), 23% (on Day 6), 7% (on Day 6), respectively]. In colon tumors, only a trend to significance was observed after SIVB PM00104 administration [lowest ratio deltaT/deltaC = 47% (on Day 7)] for the sample size tested (i.e., N = 5). With regard to gender-specific malignancies, PM00104 significantly inhibited prostate tumors [lowest ratio ?T/?C = 1% (on Day 7)], but was inactive against ovarian tumors. In summary, PM00104 demonstrated strong antitumor activity in breast, gastric, prostate, and renal, but had a more moderate antitumorigenic profile against colon.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]