Table 1.

Lesions and findings in mice treated with sapanisertib and/or trametinib for up to 21 days.

Sapanisertib 2 mg/kg dailySapanisertib 2 mg/kg EODSapanisertib 2 mg/kg EOD trametinib 5 mg/kg daily
Lesion/feature severityaLesion/feature severityaLesion/feature severitya
No lesion++++++No lesion++++++No lesion++++++
Bone marrowHypocellularity3b2541
Renal tubulesZonal cortical degeneration/necrosis11355
Scattered isolated necrosis and regeneration51414
SpleenRed and white pulp hypocellularity12255
Lymphocytolysis5235
Lymphoid and hematopoietic hyperplasia23c235
LiverHepatocelluar vacuolation211155
  • Note: Vehicle- and trametinib-treated mice had no significant lesions. Minimal splenic hyperplasia, including well-developed marginal zones and hematopoiesis was uniformly present in these mice.

  • Abbreviation: EOD, every other day.

  • aSeverity: + minimal, ++ moderate, +++ severe.

  • bNumbers of animals with described feature/severity; n = 5 per treatment; group blank = 0.

  • cPlus evidence of cell turnover.