The in vitro activity of ABT-773 was evaluated against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis isolates. ABT-773 was the most active antimicrobial tested against S. pneumoniae. ABT-773 and azithromycin were equivalent in activity against H. influenzae and M. catarrhalis and more active than either clarithromycin or erythromycin.

The anti-apoptotic proteins Bcl-XL and Bcl-2 are abundantly expressed in hematopoietic stem cells and/or progenitor cells. Furthermore, leukemic cells expressing these proteins are enriched in minimal residual disease cell populations. This prompted us to test the BH3-mimetic compound ABT-737 for its ability to eradicate putative leukemic stem cells. ABT-737 demonstrated potent cytotoxic effect...

Chronic lymphocytic leukemia (CLL) characteristically maintains high levels of the anti-apoptotic protein Bcl-2, thus protecting them from apoptotic death and leading to an accumulation of mature resting B cells. Many other hematopoietic malignancies including acute promyelocytic leukemia (APL) also depend upon Bcl-2 family proteins for survival, suggesting that Bcl-2 proteins are excellent tar...

To understand the molecular basis for variable sensitivity to the BH3 mimetic drug ABT-737, the abundance of Bcl-2 family members was assayed in a panel of small cell lung cancer cell lines whose sensitivity varied over a 2-log range. Elevated Noxa and Bcl-2 levels directly correlated with sensitivity to ABT-737, whereas Mcl-1 levels were similar in all cell lines tested regardless of sensitivi...

Despite clinical efficacy, current approved agents targeting EGFR are associated with on-target toxicities as a consequence of disrupting normal EGFR function. MAb 806 is a novel EGFR antibody that selectively targets a tumor-selective epitope suggesting that a mAb 806-based therapeutic would retain antitumor activity without the on-target toxicities associated with EGFR inhibition. To enable c...

PURPOSE Microtubules play a critical role in many cellular functions, including cell division and mitosis. ABT-751 is a novel sulfonamide antimitotic that binds to the colchicine site on beta-tubulin that leads to a block in the cell cycle at the G2M phase, resulting in cellular apoptosis. ABT-751 was investigated in this phase 1 trial designed to assess its maximum tolerated dose (MTD), dose-l...

Vicinally disubstituted pyridazinones act as potent and selective COX-2 inhibitors. Compound, ABT-963, (2-(3,4-difluoro-phenyl)-4-(3-hydroxy-3-methyl-butoxy)-5-(4-methanesulfonyl-phenyl)-2H-pyridazin-3-one) has an excellent selectivity (ratio of 276, COX-2/COX-1), improved aqueous solubility compared with celecoxib and rofecoxib, high oral anti-inflammatory potency and gastric safety in the ani...

PURPOSE The effective treatment of ovarian cancer is hampered by the development of drug resistance, which may be mediated by members of the Bcl-2 family of apoptosis regulators. ABT-737 is a recently described inhibitor of members of this family. We investigated whether this compound could sensitize ovarian cancer cells to chemotherapeutic agents. EXPERIMENTAL DESIGN The sensitivity of ovari...

Cure rates for acute myeloid leukemia (AML) remain suboptimal; thus new treatment strategies are needed for this deadly disease. Poor clinical outcomes have been associated with overexpression of the anti-apoptotic Bcl-2 family proteins Bcl-2, Bcl-xL, and Mcl-1, which have garnered great interest as therapeutic targets. While the Bcl-2-selective inhibitor ABT-199 has demonstrated promising prec...