A novel inhibitor of homeodomain interacting protein kinase 2 mitigates kidney fibrosis through inhibition of the TGF-β1/Smad3 pathway
Homeodomain interacting protein kinase 2 (HIPK2) is a critical regulator of multiple
profibrotic pathways, including that of TGF-β1/Smad3. Genetic ablation of HIPK2 was shown
previously to significantly reduce renal fibrosis in the experimental unilateral ureteral
obstruction model and Tg26 mice, a model of HIV-associated nephropathy. To develop
specific pharmacologic inhibitors of HIPK2 for antifibrotic therapy, we designed and
synthesized small molecule inhibitor compounds on the basis of the predicted structure of …
profibrotic pathways, including that of TGF-β1/Smad3. Genetic ablation of HIPK2 was shown
previously to significantly reduce renal fibrosis in the experimental unilateral ureteral
obstruction model and Tg26 mice, a model of HIV-associated nephropathy. To develop
specific pharmacologic inhibitors of HIPK2 for antifibrotic therapy, we designed and
synthesized small molecule inhibitor compounds on the basis of the predicted structure of …