Epelsiban (GSK557296), a pyridyl-2,5-diketopiperazine, is a potent, highly selective, and orally bioavailable non-peptide oxytocin receptor antagonist. GlaxoSmithKline was developing epelsiban for the treatment of women infertility due to adenomyosis and premature ejaculation.

Ralimetinib (LY2228820), a trisubstituted imidazole derivative, is a potent and selective, ATP-competitive inhibitor of the α- and β-isoforms of p38 mitogen-activated protein kinase. LY2228820 produced significant tumor growth delay in multiple in vivo cancer models (melanoma, non-small cell lung cancer, ovarian, glioma, myeloma, breast). Eli Lilly is developing ralimetinib for the treatment of cancer.

Libecillide is a specific monovalent penicilloyl hapten inhibitor of allergic reactions to penicillin. A depression of skin hypersensitivity to PPL and/or penicillin and penicillin derivatives sometimes persisting for weeks and months was obvious in numerous allergic patients submitted to combined libecillide-penicillin treatment. A depressing effect on antipenicillin antibody titers detected by passive hemaglutination was also manifest in some patients. The overall tolerance of libecillide in allergic patients has been very good. Nevertheless, the major obstacle to a wider general use of libecillide at the present time appears to be the occurrence of positive skin reactions to that compound in approximately 5 percent of patients allergic to penicillin.

Mapracorat (BAY-865319, BOL-303242-X or ZK-245186) is a selective non-steroid glucocorticoid receptor agonist exerting anti-inflammatory activity. Mapracorat showed partial attenuation of the classical NF-κB pathway, consistent with traditional steroids. However, mapracorat uniquely potentiated a novel anti-inflammatory mechanism through rapid upregulation of RelB, an anti-inflammatory member of the NF-κB alternative pathway. Mapracorat was being studied in the treatment of ocular and skin inflammatory diseases.

Pytamine is a nitrosamine derivative patented by Hercules Powder Co. as antioxidants, stabilizers, rubber additives, insecticides, fungicides, bactericides, and pharmaceutical intermediates. In preclinical trials Pytamine shows potent psychotropic effects associated modulation of GABAA receptors.

Fospirate is an organophosphorus insecticide used in veterinary as an anthelmintic agent.

Gomisin A (BESIGOMSIN/GA) one of the major dibenzocyclooctadiene lignans isolated from Schisandra chinensis Baill, has proved to possess a variety of pharmacological effects. It has been found to promote hepatocyte growth factor, limit lipid peroxidation, and inhibit apoptosis in acute hepatic injury animal models. Besigomsine also acts as an anti-inflammatory by preventing the release of arachidonic acid in macrophages in vitro. Laboratory evidence suggests that Besigomsine may have anticarcinogenic effects. Chronic administration of Gomisin A had an antihypertensive effect in AngII-induced hypertensive mice. Gomisin A may exert neuroprotective effects by attenuating the microglia-mediated neuroinflammatory response via inhibiting the TLR4-mediated NF-κB and MAPKs signaling pathways. Also it induces marked protective effects against hepatic and renal injury induced by CCl(4) exposure through differential regulation of the MAPK signal transduction pathway.

Adibendan [BM 14478] is a phosphodiesterase inhibitor that increases the calcium sensitivity of the myocardium. Adibendan selectively inhibited phosphodiesterase III (PDE III) activity concentration-dependently (IC50 = 2.0 umol/l). The IC50 values for the inhibition of PDE I or II were more than 60-fold higher. Adibendan has both vasodilator and positive inotropic properties. Adibendan was investigated as the potential treatment of heart failure and ischaemic heart disorders. However, research has been discontinued at phase II of development.

Sonolisib (PX-866) is a small-molecule inhibitor of the alpha, gamma, and delta isoforms of phosphoinositide 3-kinase (PI3K) with potential antineoplastic activity. Sonolisib inhibits the production of the secondary messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3) and activation of the PI3K/Akt signaling pathway, which may result in inhibition of tumor cell growth and survival in susceptible tumor cell populations. Inhibition of the PI3K pathway with Sonolisib leads to inhibition of cell growth and decreased activation of downstream targets in GBM, both in vitro and in vivo, using U87–tumor-bearing mice, including Akt, S6, and mTOR. Sonolisib was in phase II clinical trials by Oncothyreon for the treatment of glioblastoma multiforme and castration-resistant prostate cancer (CRPC). It was in phase I/II clinical trials for the treatment of malignant melanoma, non-small cell lung cancer and Head and neck cancer. In clinical trials, Sonolisib was well tolerated, with common side effects being diarrhea, nausea, vomiting, and elevated liver enzymes. However, no recent development has been reported.

Inecalcitol is a calcitriol analog with potential antineoplastic activity patented by a global pharmaceutical company Laboratoire Theramex. Inecalcitol is a potent agonist of vitamin D receptor (VDR). Inecalcitol was shown to be more potent than calcitriol in decreasing tumor cell growth and inducing apoptosis in a number of different model systems including models of breast cancer, prostate cancer, and squamous cell cancer. Importantly, at the doses shown to induce tumor regression in the animal models investigated, Inecalcitol had no major effect on blood calcium levels. In this phase I study, Inecalcitol was found to be well tolerated. Currently, Inecalcitol in combination with the cytotoxic drug, decitabine is undergoing a phase II clinical trial in patients with acute myeloid leukemia who are unfit to receive standard chemotherapy.