MK-1903 is a potent and selective hydroxycarboxylic acid receptor 2 (HCA2, GPR109A) full agonist. Exhibits no binding at the GRP109B receptor. This drug had been in phase II clinical trial for the treatment of atherosclerosis and Dyslipidemia. But then, according to Merck, elevation of HDL cholesterol relative to placebo did not meet the trial's pre-specified primary objective for efficacy; no safety signals were implicated as drivers of the decision to discontinue development.

MK 3577 is an orally active glucagon receptor antagonist which was under development by Merck & Co for the treatment of type 2 diabetes mellitus. MK 3577 demonstrate activity in cellular models and preclinical trials. In phase II clinical trials MK 3577 shows good efficacy and acceptable level of adverse events, but no further development reports were published.

(S,R)-3-Phenyl-4,5-dihydro-5-isoxasole acetic acid (VGX-1027, GIT-027) is an isoxazole compound that exhibits various immunomodulatory properties. This compound reduced the secretion of IL-1beta, TNF-alpha and IL-10 from purified murine macrophages stimulated "in vitro" with lipopolysaccharide (LPS), and it also modified the signaling pathways induced in these cells by LPS entailing reduced activation of NF-kappaB and p38 MAP kinase pathways along with up-regulation of ERK pathways. The animals receiving VGX-1027 exhibited reduced production of the proinflammatory mediators tumor necrosis factor-alpha, IL-1beta, macrophage migration inhibitory factor, and inducible nitric-oxide synthase-mediated nitric oxide generation in both pancreatic islets and peripheral compartments. Inovio Pharmaceuticals is developing VGX-1027 for the treatment of inflammatory conditions such as rheumatoid arthritis, type 1 diabetes mellitus, uveitis and ulcerative colitis.

PL-3994 is a novel natriuretic cyclic peptide. It is a receptor-A (NPR-A) and receptor-C (NPR-C) agonist. PL-3994 has high affinity for recombinant human, dog, or rat NPR-As. PL-3994 produced concentration-dependent relaxation of pre-contracted guinea-pig trachea. PL-3994 elicited a potent, concentration-dependent but small relaxation of pre-contracted human precision-cut lung slices. Intratracheal PL-3994 produced a dose-dependent inhibition of the bronchoconstrictor response evoked by aerosolized methacholine, but was without significant effect on cardiovascular parameters. PL-3994 was resistant to degradation by human neutral endopeptidase. PL-3994 was well tolerated in subjects with controlled hypertension. A phase I and phase II trial have been successfully completed with PL-3994 with no safety concerns identified. In phase II study in subjects with hypertension who were receiving >1 antihypertensive medications, a significant reduction in blood pressure compared with placebo was observed. It appears that PL-3994 works synergistically with ACE inhibitors.

MK-6325 is a potent HCV NS3/4A protease inhibitor patented by Merck Sharp & Dohme Corp for treating or preventing HCV infections. In 2011 MK-6325 was studied in phase I clinical trials but no further development reports were published.

PBT-1033, also known as PBT-2, is a neural protective agent potentially for the treatment of Alzheimer's disease and Huntington's Disease. PBT-1033 is a moderate-affinity 8-hydroxyquinoline transition metal-ligand that acts as a synthetic chaperone, re distributing copper, zinc, and iron from locations where they are abundant to subcellular locations where they might be deficient. Delivery of copper and zinc by PBT-1033 into the cytoplasm deactivates the kinase glycogen synthase kinase 3β and the phosphatase calcineurin, both potential targets for Huntington’s disease. In aged wild-type mice, PBT-1033 improves cognitive ability and markers of neuronal plasticity and function. In Alzheimer’s disease mouse models, PBT-1033 inhibits the accumulation of amyloid β, attenuates neuropathological effects of amyloid β, including amyloid-β-induced hyperphosphorylation of tau, and improves cognition. In a 12-week, phase 2a, randomized, double-blind, placebo-controlled trial in 78 individuals with mild Alzheimer’s dementia, PBT-1033 was safe and well tolerated and significantly reduced concentrations of amyloid β42 in CSF.

Othera Pharmaceuticals originally developed OT-730 (now known as QLT 091568) as an oculoselective beta-blocker for reducing the elevated intraocular pressure associated with glaucoma. OT-730 was involved in phase II clinical trial in patients with ocular hypertension or open-angle glaucoma. However, these studies were discontinued. At December 30, 2009, QLT Inc. acquired OT-730.