Edivoxetine (LY-2216684) is a highly selective norepinephrine reuptake inhibitor. It is under development as adjunctive or monotherapy of disorders believed to be associated with alterations in norepinephrine transmission within the central nervous system. Currently, edivoxetine is being studied in the treatment of attention-deficit hyperactivity disorder. Edivoxetine development in the treatment of major depressive disorder has been discontinued.

Semagacestat (LY-450139) was a gamma secretase inhibitor being developed as a treatment for Alzheimer's disease by Eli Lilly. It was hoped that the drug would help to delay the onset of severe Alzheimer's disease, and thereby help preserve cognitive and executive functioning and in turn improve patient quality of life. Semagacestat (LY-450139) is designed to inhibit gamma secretase, an enzyme that is involved in the cleavage of APP to beta-amyloid. By decreasing production of beta-amyloid, it is hoped that gamma secretase inhibitors will exert a disease-modifying effect in Alzheimer's disease and thus slow or halt the destruction of nerve cells – the final stage in the amyloid cascade hypothesis. In March 2008 semagacestat (LY-450139) advanced to Phase III development, where it was evaluated in the IDENTITY (Interrupting Alzheimer's Dementia by EvaluatiNg Treatment of AmyloId PaThologY) trial, the first Phase III trial for this new anti-dementia drug. In August 2010, Eli Lilly announced its decision to halt the development of Semagacestat. The decision was taken after analysing the preliminary results of the second Phase III clinical trial of the drug, which indicated that semagacestat failed to slow disease progression. The drug, in fact, worsened cognition and the ability to perform day-to-day activities.

Tazomeline (also known as LY 287041), a neuropsychiatric agent, is a muscarinic M1 acetylcholine receptor agonist that was studied in patients with cognitive dysfunction. Tazomeline participated in clinical trials for the treatment of Alzheimer’s disease and dementia. However, all these studied were discontinued for unknown reasons.

Ruboxistaurin is an orally bioavailable, selective, potent inhibitor of protein kinase C β developed for treating diabetic retinopathy. In vitro and in vivo non-clinical models have demonstrated that Ruboxistaurin decreases PKC β activity and ameliorates many of the effects of PKC β on pathologic processes in the retina. Ruboxistaurin prevents the slowing of retinal blood flow that is observed by fluorescein video angiography in the eyes of diabetic rats. It is also reported to cause regression of retinal neovascularization produced by laser-induced major branch vein occlusions in a porcine model. Ruboxistaurin positively affected the diabetes-induced retinal blood flow abnormalities in a Phase Ib study in diabetic patients. Ruboxistaurin is in phase III clinical trials for the treatment of diabetic nephropathy and diabetic macular edema. Eli Lilly had submitted Ruboxistaurin for approval in the US and the EU; however, the company subsequently discontinued development as it was unable to demonstrate sufficient efficacy

LANEPITANT is a selective nonpeptide antagonist for the neurokinin-1 receptor. It inhibits neurogenic dural inflammation. LANEPITANT was under development as a potential analgesic drug for the treatment of migraine, arthritis and diabetic neuropathy. However, it failed to show sufficient efficacy to support further development.

LY377604 is a human β3-adrenergic receptor agonist and β1- and β2-adrenergic receptor antagonist with no sympathomimetic activity at the β1- and β2-adrenergic receptors. Combination of LY377604 and a norepinephrine-serotonin uptake inhibitor (sibutramine) was studied in the treatment of obesity. LY377604 would ameliorate side effect of sibutramine treatment (increase in blood pressure and heart rate due to activation of the sympathetic nervous system).

LY404039 [(-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]-hexane-4,6-dicarboxylic acid] is an agonist of orthosteric metabotropic glutamate receptor (mGluR)2/3. In addition, it acts as an agonist at dopamine D2 receptors. LY404039 demonstrated broad antipsychotic and anxiolytic efficacy across multiple animal models. LY-2140023 is a methionine amide prodrug of LY-404039 being developed by Eli Lilly & Co for the potential oral treatment of schizophrenia.

Tasisulam sodium, previously known as LY573636, were initially recognized by Eli Lilly for their significant antiproliferative activities in solid tumor cell lines, but their mechanism of action was unknown. Subsequent studies have revealed that LY573636 induces apoptosis via a mitochondrial-mediated mechanism that appears unique among other anti-cancer compounds. This drug was in the phase III clinical trial for the treatment of Metastatic Melanoma and in phase II for the treatment Non-Small-Cell Lung Cancer, breast cancer, ovarian cancer, but these studies were discontinued. In vivo pharmacokinetic studies in rats and dogs indicate that tasisulam is metabolized primarily by the liver, and has low total plasma clearance with a relatively long half-life. In addition, there was preclinical evidence of a correlation between the maximum plasma concentration (Cmax) of tasisulam and toxicity.

Galunisertib is a potent inhibitor of TGF beta type 1 receptor. The drug is under clinical development for the treatment of different cancers: pancreatic, hepatocellular, breast, rectal, prostate etc. and reached phase 2/3 in patients with myelodysplastic syndromes.

Ruboxistaurin is an orally bioavailable, selective, potent inhibitor of protein kinase C β developed for treating diabetic retinopathy. In vitro and in vivo non-clinical models have demonstrated that Ruboxistaurin decreases PKC β activity and ameliorates many of the effects of PKC β on pathologic processes in the retina. Ruboxistaurin prevents the slowing of retinal blood flow that is observed by fluorescein video angiography in the eyes of diabetic rats. It is also reported to cause regression of retinal neovascularization produced by laser-induced major branch vein occlusions in a porcine model. Ruboxistaurin positively affected the diabetes-induced retinal blood flow abnormalities in a Phase Ib study in diabetic patients. Ruboxistaurin is in phase III clinical trials for the treatment of diabetic nephropathy and diabetic macular edema. Eli Lilly had submitted Ruboxistaurin for approval in the US and the EU; however, the company subsequently discontinued development as it was unable to demonstrate sufficient efficacy