Metynodiol, a progestin agent that has never been marketed.

BVD-523 potently and selectively inhibits ERK1 and ERK2 kinases in a reversible, ATP-competitive fashion. Consistent with its mechanism of action, BVD-523 inhibits signal transduction, cell proliferation, and cell survival, most potently in cell lines bearing mutations that activate MAPK pathway signaling. Similarly, single-agent BVD-523 inhibits tumor growth in vivo in BRAF-mutant melanoma and colorectal xenografts as well as in KRAS-mutant colorectal and pancreatic models. BioMed Valley Discoveries is developing ulixertinib, a potent and selective small molecule inhibitor of ERK 1 and 2 kinases, as an oral treatment for cancers harbouring mutations in the MAPK signaling pathway. Phase I/II development of the drug for advanced cancers including, acute myeloid leukaemia and myelodysplastic syndromes is underway in the US. A phase I trial is underway in the US for pancreatic cancer.

LXR-623 is a is a highly selective and orally bioavailable synthetic agonist of Liver X receptors (LXR) alpha and beta that has shown promise in animal models of atherosclerosis. In nonhuman primates with normal lipid levels, LXR-623 significantly reduced total (50-55%) and LDL-cholesterol (LDLc) (70-77%) in a time- and dose-dependent manner and increased expression of the target genes ABCA1 and ABCG1 in peripheral blood cells of rats, mice and monkeys. LXR-623 demonstrated efficacy for reducing lesion progression in the murine LDLR(-/-) atherosclerosis model with no associated increase in hepatic lipogenesis either in this model or Syrian hamsters and displayed a unique and favorable pharmacological profile suggesting it may be suitable for evaluation in patients with atherosclerotic dyslipidemia. Results from a single ascending-dose study of the safety, pharmacokinetics, and pharmacodynamics of LXR-623 in healthy humans confirmed the effect of LXR-623 concentration on ABCA1 and ABCG1 expression. LXR-623 was absorbed rapidly with peak concentrations (Cmax) achieved at about 2 hours and increased Cmax and area under the concentration-time curve in a dose-proportional manner. The mean terminal disposition half-life was between 41 and 43 hours independently of dose. Central nervous system—related adverse events were observed at the 2 top doses tested. LXR-623 showed brain penetration and caused tumor regression in a glioblastoma (GBM) mouse model which characterize it as a potentially potent, highly-specific anti-GBM therapy.

Arverapamil (brand name Rezular), a modulator of melatonin and serotonin receptors, was developed by Ireland-based company, AGI Therapeutics. The drug participated in phase III of clinical trials for patients to treat the irritable bowel syndrome with diarrhea, the trial was discontinued because the drug didn’t meet the primary endpoint.

CP-461 is an orally bioavailable second-generation apoptotic antineoplastic drug and analog of the nonsteroidal anti-inflammatory drug sulindac. CP-461 is an inhibitor of monophosphate-phosphodiesterase, an enzyme that inhibits the normal apoptosis signal pathway. Inhibition of cGMP-PDE permits the apoptotic signal pathway to proceed unopposed, resulting in apoptotic cell death. CP-461 was initially developed by OSI Pharmaceuticals, and in the early 2000s, CP-461 was investigated in phase I and phase 2 clinical trials for the treatment of chronic lymphocytic leukemia, Crohn's disease, malignant melanoma, renal cell carcinoma, and prostate cancer, both alone and in combination with other chemotherapeutic agents. The coadministration of CP-461 with other agents, however, did not increase the response rate. CP-461 was licensed to Celek Pharmaceuticals, where the compound was repurposed for the treatment of bladder cancer, but no development was reported.

Soravtansine (DM4-SULFO-TBA), a maytansinoid derivative, is an antineoplastic agent. Antibody–maytansinoid conjugates (like Mirvetuximab soravtansine) are in clinical trials for the treatment of various cancers. Thus, Mirvetuximab soravtansine (IMGN853) is an antibody-drug conjugate (ADC) that targets FRα (folate receptor alpha) for tumor-directed delivery of the maytansinoid DM4, a potent agent that induces mitotic arrest by suppressing microtubule dynamics.

Dioxaphetyl butyrate is a synthetic narcotic analgesic and spasmolytic agent that has no accepted medicinal value in the United States. This opioid drug under international control according to the UN Single Convention 1961 and its amendments, Schedule I.