Igmesine is a sigma-1 receptor agonist. It was assayed in clinical trials targeting major depressive disorder. Igmesine is the only antisecretory agent that we have tested to date that inhibits both cholera toxin and the E. coli enterotoxins. Sigma receptors are known to be present on nerves in the enteric nervous system and this would seem to be a potentially useful class of drugs to pursue for the treatment of secretory diarrhoea in humans. It was shown that when Alzheimer's disease rats were submitted to the conditioned fear stress test, igmesine can significantly reduce the stress-induced motor suppression, indicating exogenous σ-1 receptor agonists may alleviate Alzheimer's disease-associated depressive symptoms.

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.

Ezatiostat (TLK199) [γ-glutamyl-S-(benzyl)cysteinyl-R-phenyl glycine diethyl ester] is an inhibitor of Glutathione S-transferase P1–1 (GSTπ). The drug is a peptidomimetic of GSH (glutathione), esterified to enhance cellular uptake and designed to bind to the “G-site” of GSTP1–1. Independent of catalysis inhibition, TLK199 also disrupts the protein:protein interaction site(s) between GSTP1–1 and JNK1. Telik Inc was developing TLK-199 for the potential prevention of myelosuppression in blood diseases, namely myelodysplastic syndrome.

Droxacin is quinolone antibiotic. It is topoisomerase inhibitor.

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.

Adaprolol is a beta-adrenergic antagonist that is being developed as a topical agent to treat glaucoma. Adaprolol demonstrated a safer cardiovascular profile, especially in the population over 70 years old. It was in Phase II clinical trials for the treatment of glaucoma. This research has been discontinued.

Xenbucin is an antihyperlipidemic agent. Information about the current use of this agent is not available.

Declopramide is an apoptosis inducer. Also, it inhibits NFkappaB activation by inhibition of IkappaBbeta breakdown. In preclinical research, Declopramide demonstrated strong antitumor properties. It had been in phase II clinical trials for the treatment of colorectal cancer. However, this research has been discontinued.

Imiloxan is a highly selective alpha2B adrenoceptor antagonist and was developed for depression in the 1980s. In Phase 1 clinical trials imiloxan dosing led to hypersensitivity reactions; the molecule's development was discontinued.

Canfosfamide is a modified glutathione analogue and nitrogen mustard prodrug, with potential antineoplastic activity. Canfosfamide is selectively activated by glutathione S-transferase P1-1 an enzyme that is over-expressed in many human cancers including ovarian cancer. GST P1-1-mediated cleavage leads to an active cytotoxic phosphorodiamidate alkylating metabolite that forms covalent linkages with nucleophilic centers in tumor cell DNA, which may induce a cellular stress response and cytotoxicity, and decrease tumor cell proliferation. Preclinical studies showed that canfosfamide inhibited the growth and was cytotoxic to a wide range of established cancer cell lines including those derived from ovarian cancer (OVCAR3, HEY, SK-OV-3). Canfosfamide treatment inhibited cancer cell proliferation and induced apoptosis through the activation of the cellular stress response kinase pathway. The cytotoxic activity of canfosfamide correlated with the expression of GST P1-1. Cancer cells in which GST expression levels were increased by transfection with the GST P1-1 gene, were more sensitive to the cytotoxic effects of canfosfamide than the parental cell lines Canfosfamide in combination with pegylated liposomal doxorubicin is well tolerated and active in platinum and paclitaxel refractory or resistant ovarian cancer.