PX-102 is a methoxyphenylcyclopropane derivative patented by Phenex Pharmaceuticals AG as Farnesoid X receptor agonists useful in the treatment and prophylaxis of FXR-mediated diseases. The Farnesoid X Receptor (FXR) is a bile acid receptor which when activated by Px-102 has a profound positive impact on cholesterol, triglyceride and glucose metabolism in liver and intestine. In preclinical studies, Px-102 potently reduces intestinal uptake of neutral lipids and cholesterol and at the same time enhances the excretion of these lipid species. In addition, Px-102 improves hepatic insulin sensitivity and shows massive hepatoprotective effects in animal models of liver cirrhosis or fibrosis. Phenex Pharmaceuticals completes a phase I trial in Healthy volunteers in Germany in 2012 and no further development report has been published.

Banoxantrone (formally known as AQ4N), a bioreductive drug that is irreversibly converted to AQ4, a stable DNA affinic cytotoxic compound. Banoxantrone is activated by haem-containing reductases such as inducible nitric oxide synthase (iNOS). In hypoxic cells, AQ4N is reduced to the topoisomerase II inhibitor AQ4. By inhibition of topoisomerase II within these hypoxic areas, AQ4N has been shown to sensitize tumors to existing chemo- and radiotherapy treatments. Novacea, the company which was responsible for clinical trials for banoxantrone had decided to scale back on its clinical development, including discontinuing the clinical trial in acute lymphoblastic leukemia and delaying the planned clinical trial in B-cell lymphoma. The company decided to continue enrollment in an ongoing Phase 1b/2a clinical trial in patients with glioblastoma multiforme. However, further information about these clinical trials are not available. Some recent experiments have shown that targeting hypoxic tumors with high levels of iNOS with a combination of AQ4N and radiotherapy could be a useful clinical therapeutic strategy.

4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN), a non-neurotoxic derivative of penclomidine, is under development by Dekk-Tec for the intravenous treatment of solid tumours. DM-CHOC-PEN is a cholesterol carbonate derivative of 4-demethylpenclomedine with potential antineoplastic alkylating activity. Upon intravenous administration of 4-demethylcholesteryloxycarbonylpenclomedine, the carbonium moiety binds to and alkylates DNA at the N7 guanine position, thereby causing DNA crosslinks. This prevents DNA replication, inhibits cellular proliferation and triggers apoptosis. In addition, due to its lipophilic cholesteryl moiety this agent is able to cross the blood brain barrier (BBB) and therefore can be given intravenously compared to other alkylating agents that need to be given intra-cranially. DM-CHOC-PEN has undergone a Phase I study (allowed enrollment of subjects with advanced cancer +/- CNS involvement) and is being evaluated in a Phase II trial in subjects with advanced cancer involving the brain. DM-CHOC-PEN has completed Phase I/II trials in humans with primary and secondary tumors involving the brain with success. Complete remissions in both primary astrocytoma and metastatic lung and leukemia malignancies.Impressive objective responses and improved PFS/overall survival have been observed in subjects with NSCLC involving the CNS.

AEOL-10150 is a small-molecule antioxidant developed by Aeolus (formerly Incara) for potential subcutaneous treatment for amyotrophic lateral sclerosis (ALS), stroke, spinal cord injury, lung inflammation, and mucositis. Structurally, AEOL-10150 functions as a superoxide-dismutase mimic and contains metalloporphyrin moiety. AEOL-10150 possess high superoxide-dismutase activity as well as catalase-like activity and has the capacity to scavenge peroxynitrite and lipid peroxides. In 2017 Aeolus Pharmaceuticals has announced that the FDA has granted Fast Track designation to AEOL 10150 for the prevention of fatal respiratory failure among patients at risk for radiation pneumonitis following a radiological/nuclear incident sufficient to cause the Acute Radiation Syndrome.

PBR28 or PBR-28, a chemical substance that binds to translocator protein TSPO, also known as Peripheral-type benzodiazepine receptor (PBR). TSPO located within the cells such as macrophages reaches high levels of expression in inflammatory conditions and thus can be a biomarker of neuroinflammation. When radioactivity in the form of carbon-11 is tagged to PBR 28 and is administered, its uptake in the inflammatory body regions can be measured using positron emission tomography (PET). PBR28 now is involved in a clinical trial to evaluate the specificity of its binding in the joints of patients with inflammatory joint disease, like rheumatoid and psoriatic arthritis.