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CB-839 shows efficacy
January 2015
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SOUTH SAN FRANCISCO, Calif.—Biotechnology company Calithera Biosciences Inc. has released preclinical data for CB-839, its lead anticancer therapeutic candidate. The compound is a potent, selective, orally bioavailable glutaminase inhibitor currently under investigation in Phase 1 clinical trials as a treatment for multiple myeloma. Myeloma cells that did not express high levels of pyruvate carboxylase proved sensitive to CB-839, and those CB-839-sensitive cells presented with different metabolic profiles from those of insensitive cells. Metabolic stress induced by CB-839 resulted in sustained inhibition of mTORC1 in sensitive cells, with downstream effects on protein synthesis, nucleotide production and glycolysis. In a separate preclinical study of CB-839’s anti-tumor activity in combination with pomalidomide, the combination demonstrated synergistic antiproliferative effects in IMiD-resistant cells. CB-839 also demonstrated significant single-agent antitumor efficacy and enhanced antitumor activity when combined with pomalidomide in a multiple myeloma xenograft model.
 
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