The present invention relates to small molecule antagonists of Bcl-2 family proteins such as Bcl-2 and/or Bcl-X.sub.L. In particular, the present invention provides non-peptide cell permeable small molecules (e.g., tricyclo-dibenzo-diazocine-dioxides) that bind to a pocket in Bcl-2/Bcl-X.sub.L that block the anti-apoptotic function of these proteins in cancer cells and tumor tissues exhibiting Bcl-2 protein overexpression. In preferred embodiments, the small molecules of the present invention are active at the BH3 binding pocket of Bcl-2 family proteins (e.g., Bcl-2, Bcl-X.sub.L, and Mcl-1). The compositions and methods of the present invention are useful therapeutics for cancerous diseases either alone or in combination with chemotherapeutic or other drugs.
This application claims priority to U.S. Provisional Patent Applications 60/330,865 filed Nov. 1, 2001, and No. 60/363,836, filed Mar. 2, 2002. The disclosures of these applications are specifically incorporated herein in their entireties.
