Avagacestat (BMS-708163) is an oral gamma secretase inhibitor designed for selective inhibition of amyloid beta (Aβ) synthesis. Avagacestat was in development by Bristol-Myers Squibb for the treatment of Alzheimer's disease (AD). Avagacestat is a potent, selective, orally bioavailable γ-secretase inhibitor of Aβ40 and Aβ42 with IC50 of 0.3 nM and 0.27 nM, demonstrating a 193-fold selectivity against Notch. In November 2012, Bristol-Myers Squibb terminated clinical trials of the drug and announced its decision to end further development of avagacestat

Atopaxar, also known as E 5555 is a novel reversible protease-activated receptor-1 (PAR-1) thrombin receptor antagonist. The inhibition of thrombin-mediated platelet activation by means of protease-activated receptor-1 inhibitors represents an attractive therapeutic option for patients with atherothrombotic disease processes. In preclinical studies, atopaxar demonstrated inhibition of thrombin receptor-activating peptides (TRAP)- and thrombin-induced platelet aggregation. Atopaxar was being developed by Eisai for acute coronary syndromes (ACS) and coronary disorders, including atherothrombosis, unstable angina pectoris and myocardial infarction. Atopaxar was in phase II clinical development in the US, EU and Japan. However, development was discontinued in May 2012.

Abexinostat (PCI-24781) is a novel, second-generation phenyl hydroxamic acid–based, orally bioavailable HDAC inhibitor that has previously been shown to have activity in vitro and in vivo against a broad array of cancers, including hematopoietic malignancies and bone and soft-tissue sarcomas. Abexinostat is a pan-HDAC inhibitor mostly targeting HDAC1 with Ki of 7 nM, modest potent to HDACs 2, 3, 6, and 10 and greater than 40-fold selectivity against HDAC8. Abexinostat exhibits potent antitumor activity against a variety of tumor cell lines with GI50 ranging from 0.15 uM to 3.09 uM. PCI-24781 also has an antiproliferative effect on HUVEC endothelial cells with GI50 of 0.43 uM. Abexinostat treatment causes dose-dependent accumulation of both acetylated histones and acetylated tubulin in HCT116 or DLD-1 cells, induces expression of p21, and leads to PARP cleavage and accumulation of the γH2AX. It has also shown good tolerability and activity in Phase I and II clinical trials against lymphoma, as well as against solid tumors in Phase-I trials. Additionally, it acts as a potent radiosensitizing agent and is synergistic with cytotoxic chemotherapy, such as doxorubicin in preclinical models.

Raxatrigine also known as GSK1014802 and CNV-1014802, is a novel analgesic under development by Convergence Pharmaceuticals for the treatment of lumbosacral radiculopathy (sciatica) and trigeminal neuralgia (TGN). It is a novel state dependent small molecule sodium channel blocker that preferentially inhibits the Nav 1.7 ion channel, a therapeutic target implicated by genetics in human pain conditions. Raxatrigine is thought to penetrate the central nervous system and block Nav channels in a novel manner. CNV1014802 was granted orphan drug designation in 2013 by the US Food and Drug Administration (FDA) for the treatment of trigeminal neuralgia.

Intepirdine, also known as SB-742457, RVT-101, was originally developed by GlaxoSmithKline (GSK) as an antagonist of the serotonin receptor 6 (5-HT6). GSK sold the rights for further study of this drug to Axovant Sciences in 2014. Intepirdine is in phase 3 clinical trial for Alzheimer's and in a phase 2 trial for dementia with Lewy bodies.

Ameltolide (ADD 75073, LY 201116) is a 4-aminobenzamide anticonvulsant patented by Research Corporation Technologies in the USA. Ameltolide is a sodium channel antagonist, it represents a potential therapy for the treatment of epilepsy. Ameltolide had been in phase I clinical trials by Research Corporation Technologies for the treatment of epilepsy. However, this research has been discontinued.

Afuresertib (GSK2110183 ) is an orally bioavailable inhibitor of the serine/threonine protein kinase Akt (protein kinase B) with potential antineoplastic activity. Afuresertib binds to and inhibits the activity of Akt, which may result in inhibition of the PI3K/Akt signaling pathway and tumor cell proliferation and the induction of tumor cell apoptosis. Activation of the PI3K/Akt signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K/Akt signaling may contribute to tumor resistance to a variety of antineoplastic agents. Preclinically, AKT inhibition by afuresertib can reverse platinum resistance in ovarian cancer cell lines isolated from patients with platinum-resistant ovarian cancer. Afuresertib is well tolerated and demonstrates clinical activity as monotherapy in heavily pretreated MM patients. Is in phase II clinical trials for Chronic lymphocytic leukaemia; Haematological malignancies; Histiocytosis.

Dofequidar (MS-209), a quinolone-derived sphingomyelin synthase inhibitor that blocks P-glycoprotein and multidrug resistance-associated protein-1, is under development by Schering for the potential treatment of multidrug resistant tumors. MS-209 had been in phase III clinical trials for the treatment of breast cancer and non-small lung cancer. But this research was discontinued in 2004. Detected adverse events are: nausea, vomiting, leukopenia, neutropenia, anorexia, constipation.

Balicatib is a potent cathepsine K inhibitor that was developed for the treatment of knee osteoarthritis. The development of Balicatib was terminated in phase II due to the occurrence of skin rashes and rarer incidences of morphea-like skin changes.

SGI-1776 is a PIM-kinase inhibitor, developed by SuperGen Inc. SGI-1176 was tested in clinical trials against relapsed/refractory leukemias, prostate cancer and Non Hodgkin's Lymphoma, but the dose limiting toxicity of cardiac QTc prolongation was identified and clinical development of SGI-1776 was terminated.