SER-100 (previously known as ZP120, Ac-RYYRWKKKKKKK-NH2) is a peripherally acting orphanin FQ/nociceptin (ORL-1) receptor agonist that is in development with Serodus Pharmaceuticals for the treatment of Isolated systolic hypertension. SER-100 is a peripherally acting, highly potent and selective NOP receptor partial agonist, which was developed by coupling a chain of six lysine residues to an existing NOP receptor partial agonist hexapeptide, Ac-RYYRWK-NH2 to improve meta-bolic stability. SER-100 has sodium-potassium-sparing aquaretic and anti-natriuretic activity. SER-100 exerts a chronic hypotensive and bradycardic effects in rodents, including models of systemic and pulmonary hypertension. SER-100 produces its cardiovascular effects, at least in part, by inhibition of cardiac and vascular sympathetic activity. In terms of clinical evaluation, SER-100 was originally assessed in a randomized, double-blind, placebo controlled Phase II trial as add-on therapy in patients with sub-acute decompensated chronic heart failure (NCT00283361); how-ever, the clinical development of the peptide for this indication was terminated prematurely due to significant hypotensive activity, primarily on systolic blood pressure (SBP). Nonetheless, as a result of this profound drop in SBP, SER-100 (10 mg, s.c., bid) was investigated in a randomized, placebo-controlled study in patients with treatment-resistant isolated systolic hypertension (NCT01987284) and found to produce a meaningful and long lasting drop in SBP(~7 mmHg) and diastolic (~4 mmHg) blood pressure (DBP),as well as being safe and well-tolerated. FDA has granted an Orphan Drug Designation for SER-100 in pulmonary arterial hypertension (PAH).