Amitivir [LY217896], an amino thiadiazole derivative, is an inhibitor of the enzyme inosine monophosphate dehydrogenase. Amitivir has activity against several influenza A and B viruses. Amitivir possesses broad antiviral activity in vitro and in animal models against or thomyxo-and paramyxoviruses. In phase I studies with healthy volunteers, single doses of up to 500 mg were well tolerated and had predictable pharmacokinetics. Oral LY217896 was in trial for prevention of experimental influenza A virus infection and illness in humans. LY217896 was associated with asymptomatic rises in serum uric acid levels and was ineffective in modifying the virologic or clinical course of experimental influenza A (H1N1) virus infection. Amitivir development was 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.

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

Enzastaurin is a serine/threonine kinase inhibitor that showed antiangiogenic, antiproliferative, and proapoptotic properties in vitro and antitumor activity in vivo in a xenograft Waldenström macroglobulinemia (WM) model. Enzastaurin (LY317615) is a potent PKCβ selective inhibitor. Enzastaurin suppresses angiogenesis and was advanced for clinical development based upon this antiangiogenic activity. Enzastaurin suppresses tumor growth through multiple mechanisms: direct suppression of tumor cell proliferation and the induction of tumor cell death coupled to the indirect effect of suppressing tumor-induced angiogenesis. Enzastaurin is an orally administered drug that was intended for the treatment of solid and haematological cancers. Enzastaurin had shown encouraging preclinical results for the prevention of angiogenesis, inhibition of proliferation and induction of apoptosis as well as showing limited cytotoxicity within phase I clinical trials. However, during its assessment in phase II and III clinical trials the efficacy of enzastaurin was poor both in combination with other drugs and as a single agent. Eli Lilly discontinued development of enzastaurin after top-line data from the double-blind, international Phase III PRELUDE trial in 758 DLBCL patients showed that enzastaurin missed the primary endpoint of improving DFS vs. placebo.

Nisoxetine, 3-(o-methoxyphenoxy)-3-phenyl-N-methyl-propyl-amine, is a most active and selective inhibitor of norepinephrine uptake, which was developed by Eli Lilly as an antidepressant drug. It was shown that nisoxetine dose-dependently reduced acute food intake and the additive effect of it was preserved in obese mice. In addition, was revealed that nisoxetine produced local but not systemic analgesia against cutaneous nociceptive stimuli in rodents. However, this drug has no clinical applications in humans.

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.

Etalocib (LY-293111 or VML 295) is a potent and orally active leukotriene B4 receptor antagonist of the biphenylphenol class. It efficiently blocks neutrophil activation and subsequent inflammation. Additionally, it exerts antineoplastic properties through induction of cell cycle arrest and apoptosis in tumor cells. Etalocib was being developed for the treatment of inflammatory diseases and solid tumors.

Enviradene (LY 127123) is a benzimidazole antiviral compound. It inhibited picornavirus replication and infection in vitro.

LY-2090314 is a GSK-3alpha and GSK-3beta inhibitor developed by Eli Lilly. Phase 2 clinical trials of LY-2090314 as a signle agenst against acute leukemia did not show clinical benefit. LY-2090314 was studied in combination pemetrexed and carboplatin against solid tumors, and in combination with FOLFOX, gemcitabine, and nab-paclitaxel against pancreatic cancer.

Calcimycin is an ionophore, polyether antibiotic from Streptomyces chartreusensis. It binds and transports calcium and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems. Calcimycin has antibiotic properties against gram-positive bacteria and fungi. Inex Pharmaceuticals Corporation (Canada) reported an innovative application of Calcimycin. "Inex" used Calcimycin as a molecular tool in order to make artificial liposomes loaded with anti-cancer drugs such as Topotecan. In in vitro fertilization (IVF) field, Ca Ionophore can be used in case of low fertilization rate after ICSI procedure, particularly with Globozoospermia (Round Head sperm syndrome), Ca Ionophore plays role in oocyte activation after ICSI. Recommended use is 0.5 microgram/ml twice for 10 min interrupted with fresh media with 30 min incubation, followed with regular injected eggs culture for IVF