Abstract: TH-PO1140
A FAK-FAT Inhibitor, UA-2012, Reduces Renal Fibrotic Remodeling in an Angiotensin II-Induced Fibrotic Model
Session Information
- CKD: Mechanisms, AKI, and Beyond - 1
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Patschke, Sasha W, The University of Arizona College of Medicine Phoenix, Phoenix, Arizona, United States
- O'Brien, Hunter, The University of Arizona College of Medicine Phoenix, Phoenix, Arizona, United States
- Jorgensen, Ashton, The University of Arizona College of Medicine Phoenix, Phoenix, Arizona, United States
- Nelson, Ronald Alvin, Faknostics, LLC, Phoenix, Arizona, United States
- Green, Brad R., Faknostics, LLC, Phoenix, Arizona, United States
- Marlowe, Timothy, The University of Arizona College of Medicine Phoenix, Phoenix, Arizona, United States
- Hale, Taben M, The University of Arizona College of Medicine Phoenix, Phoenix, Arizona, United States
Background
There are currently no drug treatments for renal fibrosis, a main pathological feature of chronic kidney disease (CKD). Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase and a key factor in the formation of Focal adhesions (FAs). FAK plays a role in cell adhesion, migration, and proliferation, and is overexpressed in both cancerous and fibrotic conditions. FAK-kinase inhibitors have had limited success as a monotherapy in clinical trials, but our group has been able to produce an inhibitor targeting the Focal Adhesion Targeting (FAT) domain of the protein, which is crucial in FA recruitment and signal transduction. Due to FAK’s pivotal role in major fibrotic processes, we hypothesize that the FAK-FAT inhibitor, UA-2012, could prove effective in disrupting fibrotic remodeling.
Methods
Rats were induced with fibrosis using an Angiotensin II (ANG II) model over 28 days. Three treatment groups were formed, with one control, one test group with ANG II, and one with ANG II dosed with UA-2012 q.o.d after 14 days. Post-sacrifice, rat body weights, tibia lengths, and kidney weights were taken. Sirius Red-stain kidney slides were analyzed to assess collagen deposition.
Results
Analysis of Sirius Red-stained tissues showed significantly reduced collagen deposition in the ANG II + UA-2012 group compared to ANG II + vehicle group in both glomerular and tubulointerstitial regions. Both post-sacrifice metrics, tibia length and body weight, showed no significant difference between control and treatment groups, reinforcing UA-2012 safety.
Conclusion
These data indicate a significant effect of UA-2012 on ANG II induced renal fibrosis and showed no significant effects on subject body weight or bone growth. Further western and PCR testing will be useful to elucidate the mechanisms involved. Target genes for RT-qPCR include but are not limited to Col1α1, Col3α1, Fn1, Actn1, MCP-1, SPP1, and Mas1, while target proteins will include TLN-1, VIN-1, PXN-1, and pFAK. Further testing including evaluation of plasma biomarkers is also planned to further elucidate drug efficacy.
Funding
- Other NIH Support