Targeting the PH/DH Domain of Tiam1 for the Treatment and/or Prevention of Bone Metastases

Case ID:
UA13-105
Invention:

Tiam1 is a highly conserved exchange factor that is over-expressed in many cancers, including prostate cancer (CRPCA). Increase in Tiam1 expression is associated with increased metastases and correlates with poor PCA patient survival prognosis. This patented technology has identified a novel compound which exhibits the ability to reduce prostate cancer bone metastasis by binding to the cPH domain of Tiam1 and inhibiting its cellular functions.
 

Background:
Prostate Cancer (PCA) is a heterogeneous disease and the 5-year survival rate for men whose cancer has metastasized at the time of diagnosis being 34%, however, if the cancer is detected prior to metastasis the 5-year survival rate increases to nearly 100%. Although most patients respond to androgen suppression by entering into clinical remission, they eventually develop more aggressive tumors that are castration-resistant PCA (CRPCA). While there are currently numerous drugs designed to inhibit metastatic cells and bone, there are currently none which target CRPCA.
 

Application: 

  • Prostate cancer - target tiam1 in order to impede tumor invasion and metastasis

Advantages:

  • In vitro assays revealed that compound TPH-9 significantly reduced the number of fillipodia:
    • At a concentration of 10 mM, TPH-9 prevented wound closure of PC-3 cells and invasion by 72.1±9.6%
    • TPH-9 induced a tumor growth delay in a PC-3 mouse xenograft study
  • Only compound which specifically targets castration-resistant prostate cancer


Patent information: issued patent #10,179,142

Patent Information:
Contact For More Information:
Tod McCauley
Assistant Director of Licensing, CALS
The University of Arizona
520-621-9493
todm@tla.arizona.edu
Lead Inventor(s):
Emmanuelle Meuillet
Sylvestor Moses
Shuxing Zhang
Keywords: