Technology ID

Novel Therapeutic Compounds for Treatment of Cancer and Immune Disorders

Lead Inventor
Wiestner, Adrian (NHLBI)
Ye, Yihong (NIDDK)
Trenkle, William (NIDDK)
Therapeutic Areas
Infectious Disease
Development Status
Lead IC
The global market for cancer therapeutics is over $40 billion and is anticipated to continue to rise in the future. There remains a significant unmet need for therapeutics for cancers that affect blood, bone marrow, and lymph nodes and the immune system, such as leukemia, multiple myeloma, and lymphoma. The proteasome inhibitor bortezomib, which may prevent degradation of pro-apoptotic factors permitting activation of programmed cell death in neoplastic cells dependent upon suppression of pro-apoptotic pathways, has been a successful mode of treatment for such cancers. However, some patient’s cancers have been found to be resistant to the drug.

Researchers at the National Institutes of Health have developed novel hydrazone and diacyl hydrazine compounds that are inhibitors of the endoplasmic reticulum-associated protein degradation (ERAD) pathway. These compounds preferentially target the proteasome assistant ATPase p97/VCP at a site independent of nucleotide binding. The researchers have shown that these ERAD inhibitors can induce cancer cell death and can also synergize with bortezomib in cytotoxic activity. In addition to treating diseases or disorders in which inhibition of the ERAD pathway is an effective therapy, these novel compounds may also be useful in the study of protein degradation.
Commercial Applications
  • Development of therapies against tumors that are resistant to bortezomib
  • Use in therapies in combination with proteasome inhibitors
  • Development of immunosuppressive therapies that target the ubiquitin proteasome system
  • Studies of the mechanism of protein degradation and other biological processes that involve the p97 ATPase
  • Bioprobes to detect endoplasmic reticulum (ER) structures in live cells
Competitive Advantages
  • Potent anti-tumor activity
  • Simpler chemical structure makes synthesis easier and more cost-effective than previous ERAD inhibitors
  • Retain activity against bortezomib-resistant cells and can synergize with bortezomib
  • Fluorescent
  • High affinity for the ER
Licensing Contact:
Choudhry, Vidita
Phone: 301-594-4095