CYR-101 (MIN-101) is a cyclic amide derivative that has high equipotent affinities for 5-HT2A and sigma-2 receptors (Ki of 7.53 nM and 8.19 nM for 5-HT2A and sigma-2, respectively). MIN-101 also shows binding affinity for a1-adrenergic receptors but low or no affinity for muscarinic, cholinergic, and histaminergic receptors. MIN-101 demonstrated statistically significant efficacy in reducing negative symptoms and good tolerability in stable schizophrenia patients. The drug is in phase II clinical trials for the treatment of Schizophrenia.

MK-2206 is an oral selective allosteric inhibitor of Akt that targets all three isoforms of human Akt (Akt-1, Akt-2 and Akt-3). In a phase I study of solid tumors, MK-2206 demonstrated evidence of target modulation and anti-proliferative activity as a single agent and in combination with other agents. Current ongoing trials of MK-2206 include monotherapy and combination therapy in breast cancer, colorectal cancer, haematological malignancies, non-small cell lung cancer and other. Detected treatment-related adverse event are: rash, fatigue, hyperglycemia.

ABT-751 is an orally bioavailable antimitotic sulfonamide, which binds to the colchicine-binding site on beta-tubulin and inhibits the polymerization of microtubules, leads to a block in the cell cycle at the G2M phase, resulting in cellular apoptosis. ABT-751 had been in phase Ⅱ clinical studies for the treatment of breast cancer; colorectal cancer; non-small cell lung cancer; renal cancer, prostate cancer, but these researches have been discontinued.

BGT 226 is an orally available, small molecule, the dual inhibitor of mammalian target of rapamycin (mTOR) and phosphatidylinositol 3'kinase (PI3K), developed by Novartis for the treatment of solid tumors, including advanced breast cancer. A phase I/II trial was completed in the US, Canada, and Spain, and a phase I trial was completed in Japan. However, development appears to have been discontinued.

CUDC-101 is a multi-targeted agent designed to inhibit epidermal growth factor receptor (EGFR), human epidermal growth factor receptor Type 2 (Her2) and histone deacetylase (HDAC). This drug synergistically blocked key regulators of EGFR/HER2 signaling pathways, also attenuating multiple compensatory pathways, such as AKT, HER3, and MET, which enable cancer cells to escape the effects of conventional EGFR/HER2 inhibitors. Thus, a single compound may offer greater therapeutic benefits, which is verified in clinical trial phase I for the treatment patients with advanced head and neck, gastric, breast, liver, and non-small cell lung cancer tumors. In April 2013, CURIS, INC determined that they would discontinue enrolling patients in phase 1 expansion trial of the intravenous formulation of CUDC-101, and that the future development of CUDC-101 would be dependent on our ability to successfully develop an oral formulation of CUDC-101. However, the efforts to develop an effective oral formulation with improved bioavailability have not resulted in significant improvements when compared to the intravenous formulation of CUDC-101. As a result, at this time CURIS no longer plan to make material investments in this program.

LY2886721 is a BACE inhibitor used for the treatment of Alzheimer's Disease. LY2886721 did not inhibit other aspartyl proteases such as cathepsin D, pepsin, and renin, and reduced Aβ in a dose-dependent manner in HEK293Swe cells and in primary neurons from PDAPP transgenic mice. LY2886721 was the first BACE inhibitor to reach Phase 2 clinical research. Lilly completed six Phase 1 studies of LY2886721’s safety, tolerability, and pharmacology in a total of 150 healthy volunteers and people with Alzheimer’s disease at doses of 1–70 mg. Single and multiple ascending oral dosing was accompanied by repeat CSF sampling in the hours and days thereafter. This was done to assess CSF penetration and target engagement by way of measuring levels of the drug, BACE1 substrate, and BACE1 cleavage products. The compound lowered CSF Aβ40, Aβ42, and sAPPβ concentrations while increasing sAPPα, consistent with expectations for BACE1 inhibition. Fourteen days of daily dosing reduced BACE1 activity by 50–75 percent, and CSF Aβ42 by 72 percent. No safety concerns were apparent in dosing up to six weeks

Oleandrin is a toxic cardiac glycoside found in oleander (Nerium oleander L.). Along with neandrin it is primarily responsible for the toxicity of the sap of oleander. Oleandrin has been used for many years in China and Russia for its properties as a cardiac glycoside, for both suicidal and therapeutic purposes as in treatment of cardiac insufficiency. Because of its properties as a cardiac glycoside, oleandrin interferes in some essential processes within the cell, the most important of these being the inhibition of the Na-K ATPase. This protein enables the cell to exchange the cations Na+ and K+ between the intercellular and extracellular spaces by which, for instance, electronic signaling is made possible in nerve cells. Oleandrin binds to specific amino acids in the protein, causing it to lose its function. After depolarization of the cell in which Na+ flows into the cell, the Na+ cannot be transported back into the extracellular membrane, causing the sodium gradient to disappear. This gradient is the driving force for other transport proteins, such as the sodium-calcium exchanger, which plays an important role in cardiomyocytes. To make muscle contraction possible, a calcium influx from the extracellular fluid into the cell is crucial. After the muscle contraction, the calcium is normally pumped out of the cell and exchanged for sodium. When the sodium gradient is depleted, calcium cannot be pumped back and, as a consequence, accumulates in the cardiomyocyte. As a result of the high calcium concentration, actin and myosin filaments will bind stronger, unable to relax properly to make a new contraction possible. This may result in cardiac arrhythmias, in the worst case decreasing cardiac output and causing a shortage in oxygen supply in vital tissues. Apart from being a potent toxic compound, it may also be used in therapeutic ways. Both oleandrin and oleandrigenin, as well as their relatives, may be able to inhibit proliferation of tumor cells and stimulate their apoptosis as a result of the high concentration of intracellular calcium. In addition, it inhibits excretion of fibroblast growth factor 2 through membrane interaction and through inhibition of the Na,K-ATPase pump. However, there are no results from clinical testing on humans that support any use as a cancer treatment. Oleandrin has been reported to be lethal, but exact dosages are not fully documented. The fatal blood concentration of oleandrin has been estimated for humans to be approximately 20 ng/ml in decreased blood by extrapolation of intoxication symptoms. Symptoms present in poisoned animals include bloody diarrhea and colic, the latter especially in horses. Because the leaf itself is quite bitter, only starving animals will be likely to eat the plant. The lethal dosage for animals is estimated to be about 0.5 mg/kg.

Motolimod (VTX-2337) is a small molecule, selective Toll-like receptor (TLR) 8 agonist has been used in trials studying phase II for the treatment of peritoneal carcinoma, Ovarian Cancer, Fallopian Tube Cancer, B-cell lymphoma, squamous cell carcinoma of the head and neck among others. Motolimod is designed to mobilize a patient's immune system by directly activating myeloid dendritic cells, monocytes, and natural killer cells. This activation results in the production of a high level of mediators known to orchestrate the integration of both the innate and adaptive anti-tumor responses to a number of cancers.

LANOPEPDEN is an inhibitor of peptide deformylase, a bacterial enzyme required for protein maturation. It was in development for the treatment of complicated bacterial skin infection and hospitalized community-acquired pneumonia.