Lysergide (LSD) is a semi-synthetic hallucinogen and is one of the most potent drugs known. Recreational use became popular between the 1960s to 1980s, but is now less common. LSD was first synthesized by Albert Hoffman while working for Sandoz Laboratories in Basel in 1938. Some years later, during a re-evaluation of the compound, he accidentally ingested a small amount and described the first ‘trip’. During the 1950s and 1960s, Sandoz evaluated the drug for therapeutic purposes and marketed it under the name Delysid®. It was used for research into the chemical origins of mental illness. Recreational use started in the 1960s and is associated with the ‘psychedelic period’. LSD possesses a complex pharmacological profile that includes direct activation of serotonin, dopamine and norepinephrine receptors. In addition, one of its chief sites of action is that of compound-specific (“allosteric”) alterations in secondary messengers associated with 5HT2A and 5HT2C receptor activation and changes in gene expression. The hallucinogenic effects of LSD are likely due to agonism at 5HT2A and 5HT2C receptors. LSD is also an agonist at the majority of known serotonin receptors, including 5HT1A, 5HT1B, 5HT1D, 5HT5A, 5HT6 and 5HT7 receptors. During the 1960s, LSD was investigated for a variety of psychiatric indications, including the following: as an aid in treatment of schizophrenia; as a means of creating a "model psychosis"; as a direct antidepressant; and as an adjunct to psychotherapy. LSD is listed in Schedule I of the United Nations 1971 Convention on Psychotropic Substances.

Edaglitazone have a clear PPAR-gamma agonist profile, with predominant PPAR-gamma activity and little PPAR-alpha activity. Edaglitazone was reported to significantly improve insulin sensitivity and enhance the rate of glucose oxidation in both the presence and absence of insulin. Additional studies have shown that edaglitazone affects muscle glucose metabolism by additional mechanisms other than PPAR-gamma activation. Phase I clinical studies have revealed that edaglitazone is well-tolerated and capable of significantly improving glucose homeostasis. Edaglitazone had been in phase II clinical trials for the treatment if type 2 diabetes. However, this research has been discontinued.

Anisodamine is a naturally occurring atropine derivative that has been isolated, synthesized and characterized by scientists in the People's Republic of China. Anisodamine is a non-specific cholinergic antagonist. Anisodamine has been shown to interact with and disrupt liposome structure which may reflect its effects on cellular membranes. Experimental evidence implicates anisodamine as an anti-oxidant that may protect against free radical-induced cellular damage. Its cardiovascular properties include depression of cardiac conduction and the ability to protect against arrhythmia induced by various agents. Anisodamine is a relatively weak alpha(1) adrenergic antagonist which may explain its vasodilating activity. Its anti-thrombotic activity may be a result of inhibition of thromboxane synthesis. Numerous therapeutic uses of anisodamine have been proposed including treatment of septic shock, various circulatory disorders, organophosphorus (OP) poisoning, migraine, gastric ulcers, gastrointestinal colic, acute glomerular nephritis, eclampsia, respiratory diseases, rheumatoid arthritis, obstructive jaundice, opiate addiction, snake bite and radiation damage protection. The primary therapeutic use of anisodamine has been for the treatment of septic shock. Several mechanisms have been proposed to explain its beneficial effect though most mechanisms are based upon the assumption that anisodamine ultimately acts by an improvement of blood flow in the microcirculation. Preliminary studies suggest another important therapeutic use of anisodamine is for the treatment of OP poisoning. Anisodamine has been employed therapeutically since 1965 in the People’s Republic of China primarily to improve blood flow in circulatory disorders such as septic shock, disseminated intravascular coagulation (DIC) and as an antidote to organophosphate poisoning.

8-Chloroadenosine-3',5'-cyclic-monophosphate (8-Cl-cAMP), an analog of c-AMP, is a novel antineoplastic agent. It has been shown to be effective against different human cancer cell lines modulating the cellular signal transduction pathway, thereby causing growth inhibition, cell differentiation, and apoptosis. 8-Cl-cAMP preferentially binds to the R2 subunit of protein kinase A (PKA) and induces rapid R2 up-regulation and eventual R1 subunit down-regulation. It has potent inhibitory effects on a wide variety of human cancer cell lines, with an IC50 ranging from 0.1 to 20 uM. The IC50 falls with the length of drug exposure. It can suppress c-myc and c-ras proto-oncogenes in vitro and in vivo. It was shown that 8-Cl-cAMP induces cell growth inhibition through AMP-activated protein kinase (AMPK) activation with p38 MAPK acting downstream of AMPK in this signaling pathway. 8-Cl-cAMP induced apoptosis, apparently through activation of the p38 MAPK pathway by inducing progressive phosphorylation of the p38 mitogen-activated protein kinase (MAPK), via activation of AMPK by its metabolite 8-Cl-adenosine. 8-Cl-cAMP does not significantly inhibit the growth of NIH 3T3 cells, rat kidney fibroblasts, mammary epithelial cells, or peripheral blood lymphocytes, nor does it inhibit the growth of parental cells whose progeny have been transformed. Such selectivity makes it an attractive candidate for cancer therapy suggesting that it should not cause the toxicity of conventional cytotoxic agents but should inhibit tumor growth. 8-Cl-cAMP has been evaluated in phase I/II clinical trials.

Ormaplatin (NSC 363812, tetraplatin) is a stable platinum (IV) analog. Ormaplatin alkylates DNA, forming both inter- and intra-strand platinum-DNA crosslinks, which result in inhibition of DNA replication and transcription and cell-cycle nonspecific cytotoxicity. Ormaplatin showed marked antitumor activity both in vitro and vivo. The severe, cumulative and irreversible peripheral neurotoxicity observed in phase I studies resulted in termination of further clinical development of ormaplatin.

Sanguinarine is an extract of the bloodroot plant Sanguinaria canadensis, a member of the poppy family. It is an inhibitor of protein phosphatases PP1, PP2C and PP2B in vitro. Also inhibits mitogen-activated protein kinase phosphatase-1 (MKP-1) and other enzymes. Sanguinarine exerts a protective effect in cerebral ischemia, and this effect is associated with its anti-inflammatory and anti-apoptotic properties. It was clinically tested as an agent against gingivitis and tooth plaques.

Lefradafiban, an orally active prodrug of fradafiban, is a novel glycoprotein (IIb/IIIa) inhibitor for the treatment of unstable angina. The pharmacokinetic and pharmacodynamic properties of lefradafiban were assessed in 130 healthy male volunteers who received a single dose of 10, 50, 75, 100, or 150 mg or multiple doses of 25, 50, 60, 75, 90, or 100 mg three times daily for one week. After both single and multiple doses, receptor occupancy and plasma lefradafiban levels correlated with platelet aggregation. Lefradafiban had been in phase II clinical trials by Boehringer Ingelheim for the treatment of thrombosis. However, it has been terminated.

Ormaplatin (NSC 363812, tetraplatin) is a stable platinum (IV) analog. Ormaplatin alkylates DNA, forming both inter- and intra-strand platinum-DNA crosslinks, which result in inhibition of DNA replication and transcription and cell-cycle nonspecific cytotoxicity. Ormaplatin showed marked antitumor activity both in vitro and vivo. The severe, cumulative and irreversible peripheral neurotoxicity observed in phase I studies resulted in termination of further clinical development of ormaplatin.

Fluorocyclopentenylcytosine (RX-3117) is a novel small molecule nucleoside compound that is incorporated into DNA or RNA of cancer cells and inhibits both DNA and RNA synthesis which induces apoptotic cell death of tumor cells. Fluorocyclopentenylcytosine also mediates the down-regulation of DNA methyltransferase 1 (DNMT1), an enzyme responsible for the methylation of cytosine residues on newly synthesized DNA and also a target for anticancer therapies. Preclinical studies have shown Fluorocyclopentenylcytosine to be effective in both inhibiting the growth of various human cancer xenograft models, including colon, lung, renal and pancreas, as well as overcoming chemotherapeutic drug resistance. Fluorocyclopentenylcytosine has demonstrated a broad spectrum anti-tumor activity against 50 different human cancer cell lines and efficacy in 12 different mouse xenograft models. The efficacy in the mouse xenograft models was superior to that of gemcitabine. In addition, in human cancer cell lines made resistant to the anti-tumor effects of gemcitabine, Fluorocyclopentenylcytosine still retains its full anti-tumor activity. In August 2012, Rexahn reported the completion of an exploratory Phase I clinical trial of Fluorocyclopentenylcytosine in cancer patients conducted in Europe, to investigate the oral bioavailability, safety and tolerability of the compound. In this study, oral administration of Fluorocyclopentenylcytosine demonstrated an oral bioavailability of 34-58% and a plasma half-life (T1/2) of 14 hours. In addition, Fluorocyclopentenylcytosine was safe and well tolerated in all subjects throughout the dose range tested. Fluorocyclopentenylcytosine is in phase I/II clinical trials by Rexahn for the treatment of bladder cancer and pancreatic cancer. This compound was granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with pancreatic cancer in September 2014.

Poziotinib is an inhibitor of EGFR tyrosine kinase family. The drug is being tested in phase II of clinical trials for different cancers: breast cancer, lung adenocarcinoma, head and neck squamous cell carcinoma, HER-2 positive advanced gastric cancer (in combination with Paclitaxel and Trastuzumab).