GFB-8438 (30 mg/kg; s.c.; daily for 3 weeks) is efficacious in a hypertensive deoxycorticosterone acetate (DOCA)-salt rat model of focal segmental glomerulosclerosis (FSGS), significantly reducing both total protein and albumin concentrations in urine[1]. GFB-8438 (1 mg/kg; i.v.) treatment shows the Cl, VSS, and t1/2 were 31 mL/min/kg, 1.17 L/kg, and 0.5 hours, respectively[1]. Animal Model: Sprague Dawley rats (DOCA-salt rat model of FSGS)[1] Dosage: 30 mg/kg Administration: s.c.; daily for 3 weeks Result: Significant reduction in urine protein concentrations. Animal Model: 6-8 weeks old male SD rats[1] Dosage: 1 mg/kg Administration: i.v. (Pharmacokinetic Analysis) Result: The Cl, Vss, and t1/2 were 31 mL/min/kg, 1.17 L/kg, and 0.5 hours, respectively.
In Vitro
Pretreatment of mouse podocyte with GFB-8438 (1 μM for 30 min), followed by incubation with protamine sulfate, effectively blocked synaptopodin loss and cytoskeletal remodeling[1].
Kinase Assay
Cell Assay
Animal Administration
References
[1]. Yu M, et al.Discovery of a Potent and Selective TRPC5 Inhibitor, Efficacious in a Focal Segmental Glomerulosclerosis Model.ACS Med Chem Lett. 2019 Oct 22;10(11):1579-1585.
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