Select lead agonist. Renal CP toxicity reduction will be a major driver for lead selection (50% or greater protective effects on CP renal toxicity using serum creatinine, inulin based GFR, and CP-AKI injury score) selecting a peptide if it is equal or better than rRNLS. Milestone (M1): Use the improved models including ours, to compare the ED50 dose of rRNLS and 2 RNLS peptides for ability to prevent CP caused AKI and limit progression to CKD; M2: Compare rRNLS and 2 RNLS peptides in multiple dosing studies to decrease CP toxicity in our improved model and assess serum chemistries, hematology, clinical signs, body and organ weights, behavioral/physiological observations (Irwin tests), acoustic startle response, and gross autopsy observations. M3: Determine pharmacokinetics on effective agonists with longer T1/2 and greater AUC desirable. M4: Select
Select lead agonist. Renal CP toxicity reduction will be a major driver for lead selection (50% or greater protective effects on CP renal toxicity using serum creatinine, inulin based GFR, and CP-AKI injury score) selecting a peptide if it is equal or better than rRNLS. Milestone (M1): Use the improved models including ours, to compare the ED50 dose of rRNLS and 2 RNLS peptides for ability to prevent CP caused AKI and limit progression to CKD; M2: Compare rRNLS and 2 RNLS peptides in multiple dosing studies to decrease CP toxicity in our improved model and assess serum chemistries, hematology, clinical signs, body and organ weights, behavioral/physiological observations (Irwin tests), acoustic startle response, and gross autopsy observations. M3: Determine pharmacokinetics on effective agonists with longer T1/2 and greater AUC desirable. M4: Select