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KF-1607, a novel pan src kinase inhibitor, attenuates obstruction-induced tubulointerstitial fibrosis in mice
- KF-1607, a novel pan src kinase inhibitor, attenuates obstruction-induced tubulointerstitial fibrosis in mice
- Dorotea D.; Lee S.; Lee S.J.; Lee G.; Son J.B.; Choi H.G.; Ahn S.-M.; Ha H.
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- Biomolecules and Therapeutics
- Biomolecules and Therapeutics vol. 29, no. 1, pp. 41 - 51
- Chronic kidney disease; Renal fibrosis; Src kinase; Src kinase inhibitor; Ureteral obstruction
- Korean Society of Applied Pharmacology
- SCIE; SCOPUS; KCI
- Document Type
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- Src family kinases (SFKs), an important group of non-receptor tyrosine kinases, are suggested to be excessively activated during various types of tissue fibrosis. The present study investigated the effect of KF-1607, an orally active and a newly synthesized Src kinase inhibitor (SKI) with proposed low toxicity, in preventing the progression of renal interstitial fibrosis. Unilateral ureteral obstruction (UUO) surgery was performed in 6-week-old male C57BL/6 mice to induce renal interstitial fibrosis. Either KF-1607 (30 mg/kg, oral gavage) or PP2 (2 mg/kg, intraperitoneal injection), a common experimental SKI, was administered to mice for seven days, started one day prior to surgery. UUO injury-induced SFK expression, including Src, Fyn, and Lyn kinase. SFK inhibition by KF-1607 prevented the progression of tubular injury in UUO mice, as indicated by decreases in albuminuria, urinary KIM-1 excretion, and kidney NGAL protein expression. Renal tubulointerstitial fibrosis was attenuated in response to KF-1607, as shown by decreases in α-SMA, collagen I and IV protein expression, along with reduced Masson’s trichrome and collagen-I staining in kidneys. KF-1607 also inhibited inflammation in the UUO kidney, as exhibited by reductions in F4/80 positive-staining and protein expression of p-NFκB and ICAM. Importantly, the observed effects of KF-1607 were similar to those of PP2. A new pan Src kinase inhibitor, KF-1607, is a potential pharmaceutical agent to prevent the progression of renal interstitial fibrosis. © 2021 The Korean Society of Applied Pharmacology.
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