2,2′-biphenazine compounds and methods useful for treating disease
The invention relates to a chemotherapeutic cancer treatment in which compounds (BH3Is) are administered to a mammal to treat B-cell Lymphoma or other hematopoietic cancers, including diseases associated with MCL-1. The invention also provides a method for treating types of hematopoietic cancers, such as B-cell lymphoma, using a combination of one or more disclosed compounds in combination with other therapies, for example, 26S proteosome inhibitors, such as, for example, Bortezomib. The invention also relates to autoimmune treatment with pharmaceutical compositions comprising one or more disclosed compounds. The invention also relates to methods for identifying compounds, for example, compounds of the BH3 mimic class, that have unique in vitro properties that predict in vivo efficacy against B-cell lymphoma tumors and other cancers as well as autoimmune disease. Illustrative compounds are those of Formula II:
1. A compound selected from dimethyl 4,4′-diformyl-1,1′,3,3′,6,6′-hexahydroxy-[2,2′-biphenazine]-9,9′-dicarboxylate and dimethyl 1,1′,3,3′,6,6′-hexahydroxy-4,4′-bis(hydroxymethyl)-[2,2′-biphenazine]-9,9′-dicarboxylate.
2. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
3. A compound, wherein the compound is dimethyl 4,4′-diformyl-1,1′,3,3′,6,6′-hexahydroxy-[2,2′-biphenazine]-9,9′-dicarboxylate.
4. A pharmaceutical composition comprising the compound of claim 3 and a pharmaceutically acceptable carrier.
5. A compound, wherein the compound is dimethyl 1,1′,3,3′,6,6′-hexahydroxy-4,4′-bis(hydroxymethyl)-[2,2′-biphenazine]-9,9′-dicarboxylate.
6. A pharmaceutical composition comprising the compound of claim 5 and a pharmaceutically acceptable carrier.