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.

Namitecan (ST1968) is a camptothecin analogue being developed by sigma-tau (a subsidiary of Alfasigma) in Switzerland for the treatment of cancer. Namitecan, a novel hydrophilic camptothecin analog of the 7-oxyiminomethyl series, was selected for clinical development on the basis of its promising preclinical efficacy. Namitecan is a topoisomerase I inhibitor. Namitecan exhibited an acceptable toxicity profile, with neutropenia being the dose-limiting toxic effect, and clinical benefit was appreciable in patients with different tumor types, particularly bladder and endometrium carcinomas.

Prenoverine is diphenylmethanol derivative patented by Andreu, Dr. S. A. as a muscle relaxant. Prenoverine shows good multidrug resistance-reversal activity.

Azanator (previously known as Sch 15280), a bronchodilator and an antihistamine drug that acts via a non-adrenergic mechanism to block both histaminergically and cholinergically mediated responses in the tracheobronchial tree. Besides, the drug inhibits cyclic CMP phosphodiesterase. Azanator can have a therapeutic application in cases of chronic cough and cystic fibrosis in man.

Camiverine is phenylacetate derivative with cardio-vascular. Its antispasmodic action was 1/16 that of atropine (for the acetylcholine spasm) and 6.7-19.4 times that of papaverine for the BaCl2 and the histamine spasm, both tests in vitro. No chronic toxicity was observed for the oral dose of 50-100 mg/kg daily for 60 days in rats.

Trecadrine is a beta3-adrenergic agonist. Trecadrine could have normalized the oxygen consumption by the liver, in which other metabolic pathways could be involved. The administration of Trecadrine produced a statistically significant decrease in glucose levels, which is not related to changes in insulin levels. Trecadrine administration to animals significantly inhibited galactose intestinal absorption, which was independently confirmed by additional in-vitro studies and decreased disaccharidase activities. Trecadrine enhance glucose storage in liver, probably through a non-insulin dependent mechanism of action. Trecadrine administration may have a therapeutic potential in disorders associated with hypertriglyceridemia such as obesity and some types of hyperlipidaemias. Trecadrine shows a potent hypoglycaemic effect in the alloxan-induced model of diabetes in rats by decreasing hepatic glucose output and improving muscle glucose uptake.

LAGOCICLOVIR is a nucleoside reverse transcriptase inhibitor with activity against human immunodeficiency virus and hepatitis B virus.

FLUDALANINE, an analog of D-alanine, is an anti-bacterial agent active against gram-negative and gram-positive bacteria. The antibacterial action results from a sequential blockade of the D-alanine biosynthesis by irreversible inhibition of bacterial alanine racemase. Thus, FLUDALANINE blocks incorporation of D-alanine into the bacterial cell wall.

Furafylline is a methylxanthine derivative that was introduced as a long-acting replacement for theophylline in the treatment of asthma, it was a bronchodilator with extended duration compared to theophylline, but then subsequently reported the adverse side effects the inhibition of the oxidation of caffeine, a reaction catalyzed by CYP1A2. Furafylline is now widely used in biochemical studies as a selective mechanism-based inhibitor of cytochrome p450 1A2.

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.