N-QUINOLIN-BENZENSULFONAMIDES AND RELATED COMPOUNDS FOR THE TREATMENT OF CANCER, AUTOIMMUNE DISORDERS AND INFLAMMATION

摘要

The present invention relates to the NQBS class of molecules. It is based, at least in part, on the discovery that a representative group of compounds have been observed to inhibit nuclear translocation of NF-&kgr;&Bgr; subunits. Without being bound by any particular theory, this inhibition of nuclear translocation may be mediated by either (i) binding of the NQBS or related compound to the C-terminus of the RHD, which specifically mediates the nuclear internalization; or (ii) NQBS-mediated stabilization of the dimer/&Igr;&kgr;&Bgr; complex, disallowing dissociation of the active NF~KB monomers, and thus, inhibiting the generation of the subunits necessary to enter the nucleus. The NQBS class of molecules, and related molecules, may be used in therapeutic applications where inhibition of NF-&kgr;&Bgr; translocation is beneficial, including but not limited to the treatment of cancer, autoimmune disorders, and inflammatory states.