Table 1.

In vivo activity of PHA-739358

ModelDose and scheduleMaximal TGI, % (day)Maximal weight loss (%)
A2780 human ovarian carcinoma xenograft in nude mice30 mg/kg i.v. qD, D1–1080 (19)18
HCT-116 human colon carcinoma xenograft in nude mice30 mg/kg i.v. bd, D1–566 (17)22
HL-60 human acute myelogenous leukemia xenograft in SCID mice30 mg/kg i.v. bd, D1–598 (22)*16
DMBA-induced mammary carcinoma in rat25 mg/kg i.v. bd, D1–3 q wk × 275 (10)10
MMTV-RAS transgenic mammary carcinoma in mice30 mg/kg i.v. bd, D1–3 q wk × 268 (23)15
TRAMP transgenic prostate carcinoma in mice30 mg/kg i.v. bd, D1–53/16 PRND
10/16 SD
3 progressions
  • NOTE: n = 8–10 animals/study. The TGI (%) was calculated according to the equation % TGI = 100 − (mean tumor weight of treated group/mean tumor weight of control group) × 100.

  • Abbreviations: ND, not determined; qD, once a day.

  • * Two of eight animals showed complete regression.

  • One of 10 animals showed complete regression; 1/10 death at day 5.