Bionovo, Inc. (Nasdaq: BNVI) today announced the publication in the peer-reviewed, open-access journal Public Library of Science One (PLoS ONE) of a paper describing the molecular mechanisms underlying the selective cytotoxic activity of its drug candidate BN108 and its active compound, timosaponin AIII.
The mTOR complex regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and transcription. The disregulation of the mTOR pathway is implicated as a contributing factor in various cancers which makes mTORC1 an attractive therapeutic target. The endoplasmic reticulum (ER) serves many general functions, including the facilitation of protein folding and the transport of synthesized proteins to the cell membrane. ER stress is elicited by a wide variety of conditions including nutrient deprivation, impaired protein degradation or secretion, calcium imbalance and treatment with some chemotherapeutic drugs. By inhibiting mTORC1 and inducing ER stress BN108 and TAIII activate cell suicide, or apoptosis. Because these drugs do not inhibit mTORC1 and induce little ER stress in normal cells, they selectively kill tumor cells. In addition, BN108 is administered orally, which should increase its utility as an agent that can be given for extended durations for the treatment of various cancers.