GFB-8438

GFB-8438 is a potent and subtype selective TRPC5 inhibitor, with IC50s of 0.18 and 0.29 μM of hTRPC5 and hTRPC4, respectively. GFB-8438 shows excellent selectivity against TRPC6, other TRP family members, NaV 1.5, as well as limited activity against the hERG channel. GFB-8438 protects mouse podocytes from injury induced by protamine sulfate model[1].

Signaling Pathways >> Membrane Transporter/Ion Channel >> TRP Channel

Research Areas >> Others

hTRPC5:0.18 μM (IC50)

hTRPC4:0.29 μM (IC50)

rTRPC5:0.18 μM (IC50)

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].

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.

[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.