RelMD  
   
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Fig. 2.  Rel-MD targets the “Rel” family of proteins within the NF-kB signaling circuit.    NF-kB consists of Rel dimers via Rel Homology Domain (RHD).  Heterodimers that signal through the canonical path include  p65/p50, c-Rel/p50; through the non-canonical path: RelB/p52, p65/p52, c-Rel/p52

 

The abnormal activation of the NF-kB signaling circuit within a cell has been implicated in cancer, inflammation, infectious and some neurological diseases (figure 1).   At the base of this circuit is a family of 5 Rel proteins (RelA, RelB, c-Rel, p50 and p52) that bind directly to DNA and regulate the transcription of target genes (figure 2).  rel-MD, Inc. is a start-up biotechnology company that develops small molecule drugs that inhibit these Rel proteins.  The company believes that such inhibitors will offer new opportunities for effective intervention in cancer, inflammation and other diseases where dysregulation of NF-kB has been implicated.

 

To validate the target and the inhibitors, rel-MD, Inc. has developed a network of academic collaborations to test its compounds in animal models of cancer and inflammation. To date, our compounds have demonstrated efficacy in in vitro and in vivo model systems of:

  • Multiple myeloma (Dr. Ken Anderson, Dana Farber Cancer Institute, Harvard University)
  • Lung cancer (Dr. Charles Sawyers, Memorial Sloan-Kettering Cancer Center)
  • Rheumatoid arthritis (Dr. Salvotore Cuzzocria, University of Messina)
  • Radio sensitization (Dr. Barbara Durkacz, Newcastle University)
  • Infection with human T-cell lymphotrophic virus type 1 (HTLV-1) (Dr. Steve Jacobson, NINDS, NIH)
  • Blocking HIV replication (Dr. Tim Fouts, Profectus BioSciences)

 

Motivated by these results, rel-MD, Inc. has secured the exclusive worldwide rights to several families of compounds specific for the various Rel proteins.  

 

Targeting the NF-kB circuit through Rel offers several advantages.  NF-kB signaling can occur through two pathways, the canonical and noncanonical paths.  Pharmaceutical companies today have focused their efforts on developing inhibitors of the kinase proteins, such as IKKb, that regulates the NF-kB canonical pathway.  The upstream kinases are more likely to cross-react with other pathways to cause untoward side effects.  The Rel proteins, on the other hand, are the down-stream final “executors” of the NF-kB pathway.  With only 5 family members, the Company’s Rel inhibitors can be used to block signaling through either or both the canonical and non-canonical NF-kB pathway.  The selectivity of our candidates and the limited number of Rel protein targets gives rel-MD, Inc. significant advantages to develop therapeutic options that are novel, selective, and effective.