NPS-2143 is a novel potent and selective antagonist of Ca(2+) receptor with IC50 of 43 nM. Blockage of CaSR with NPS-2143 has being shown to prevent the development of pulmonary hypertension and right ventricular hypertrophy in animal models of pulmonary hypertension. The use of calcilytics, antagonists of CaSR, may be a novel therapeutic approach for PAH patients. Calcilytic drugs have been researched as potential treatments for osteoporosis, and as the first such compound developed, NPS-2143 is still widely used in research into the CaSR receptor as well as design of newer calcilytic agents. When administered together with an antiresorptive agent (estradiol), NPS 2143 causes an increase in trabecular bone volume and bone mineral density in osteopenic rats.

R-1485 is a lead candidate identified from Roche Pharmaceuticals research programme for the treatment of Alzheimer's disease. Selective and high affinity 5-HT6 antagonist; displays low hERG inhibition. Exhibits >100 fold selectivity against a panel of 50 targets including other 5-HT receptor subtypes. R-1485 is currently in Phase I trials at Roche for the treatment of Alzheimer’s type dementia. This compound showed a pKi value of 9.3 when it was tested for inhibition of [3H]-LSD binding to human 5-HT6 receptors expressed in HEK293 cells. In addition, it was also found that in rats this agent has good BBB permeability.

GW0742, also known as GW610742, is a potent and highly selective PPARβ/δ agonist, with IC50 of 1 nM, with 1000-fold selectivity over hPPARα and hPPARγ. GW0742 treatment has a prominent anti-inflammatory effect in 5XFAD mice and suggests that PPARδ agonists may have therapeutic utility in treating AD. GW0742 has the ability to improve glucose homeostasis in diabetic rats through activation of PPAR-δ. Therefore, PPAR-δ is a good target for the development of antidiabetic drugs in the future.

Caprospinol, also known as SP-233, a spirostenol derivative, protects neuronal cells against β-Amyloid (Abeta(1-42)) protein toxicity by binding to and inactivating this peptide. It was shown, that caprospinol crossed the blood-brain barrier, accumulated in the brain, and restored cognitive impairment in a pharmacological rat model of Alzheimer's disease. It was suggested, that the drug could be considered as a promising drug for Alzheimer's disease treatment.

AK-7 is a brain penetrant selective SIRT2 inhibitor. AK-7 exerts neuroprotective properties in vitro and in vivo models of neurodegenerative diseases (Huntington’s, Parkinson’s and Alzheimer’s disease).

A-582941 was found to exhibit high-affinity binding and agonism at alpha-7 nicotinic acetylcholine receptor (α7-nAChR), with acceptable pharmacokinetic properties and excellent distribution to the central nervous system. In vitro and in vivo studies indicated that A-582941 activates signaling pathways known to be involved in cognitive function such as ERK1/2 and CREB phosphorylation. A-582941 enhanced cognitive performance in behavioral assays including the monkey delayed matching-to-sample, rat social recognition, and mouse inhibitory avoidance models that capture domains of working memory, short-term recognition memory, and long-term memory consolidation, respectively. AbbVie is developing α7-nAChR agonists including A-582941 as neuroprotective agents for the treatment of cognitive disorders such as Alzheimer's disease and schizophrenia. Development is at the preclinical stage.

BAY-73-6691 is a novel, potent, and selective PDE9 inhibitor that was developed by Bayer for the treatment of Alzheimer's disease. The PDE9A enzyme is expressed primarily in the brain, with high concentrations in the cerebellum, neocortex, striatum, and hippocampus, and acts to limit the cGMP-mediated signal transduction which occurs following glutamate binding to NMDA receptors. Consequently, selective PDE9A inhibitors were predicted to prolong intracellular responses to glutamate and enhance glutamate signaling, and since this process is known to be involved in learning and memory, PDE9A inhibitors should have a nootropic effect and may be useful in the treatment of Alzheimer's. Animal studies have confirmed these expectations, and BAY 73-6691 has been shown to improve learning and memory in rats. As the first selective PDE9A inhibitor to be developed, it is also widely used in research into the function of this enzyme subtype. However pre-clinical research is at an early stage and it is not yet known whether BAY 73-6691 will prove suitable to progress to human trials, or if it will remain merely a laboratory research tool.

Eleutheroside E is one of the active constituents of the Eleutherococcus senticosus (Rupr. & Maxim.) is also called Harms (ES), Acanthopanax senticosus, Siberian ginseng, or Gasiogapi in Korea. It is a diastereoisomer of Eleutheroside D. Eleutheroside E (EE) significantly decreased the inflammatory cell infiltration, pannus formation, cartilage damage, and bone erosion of collagen-induced arthritis mice, highlighting Eleutheroside E as a potential therapeutic agent for rheumatoid arthritis. Treatment of rat mesangial cells with Eleutheroside E markedly attenuated high glucose induced cells proliferation and in a dose-dependent manner. Intervention with EE also significantly blocked high glucose induced intracellular ROS production by decreasing NADPH oxidase activity. Intervention with EE also significantly blocked high glucose induced intracellular ROS production by decreasing NADPH oxidase activity. EE mediates the hyperglycemic effects of Eleutherococcus senticosus by regulating insulin signaling and glucose utilization. The beneficial effects of EE may provide an effective and powerful strategy to alleviate diabetes. Eleutheroside E exhibited weak inhibition against CYP2C9, CYP2E1 activity, and no effect on CYP2D6 and CYP3A4. The inhibition can result in the increase of the plasma concentration and toxicity of concomitant drugs, especially for those with narrow therapeutic windows such as warfarin, phenobarbital and phenytoin.

Evodiamine, a naturally occurring indole alkaloid, is one of the main bioactive ingredients of Evodia Rutaecara, the dried unripe fruit of which is also known as Wu zhu yu (Wu Zhu Yu, interchangeably) or Evodia Fruit. Evodia Fruit used in Traditional Chinese Medicine for the purposes of warmth, intestinal comfort (specifically; to alleviate abdominal pain, acid regurgitation, nausea and diarrhea), dysmenorrheal, and fighting inflammation and infections. With respect to the pharmacological actions of evodiamine, more attention has been paid to beneficial effects in insults involving cancer, obesity, nociception, inflammation, cardiovascular diseases, Alzheimer's disease, infectious diseases and thermo-regulative effects. Evodiamine has evolved a superior ability to bind various proteins including TRPV1, the aryl hydrocarbon receptor (AhR), and topoisomerases I and II. There are currently no human studies on evodia rutaecarpa berries or evodiamine.

HX630 is a synthetic RXR pan-agonist. HX-630 has bein shown to exert anti-proliferative and pro-apoptotic effects in murine pituitary corticotroph tumor AtT20 cells, making HX-630 a new therapeutic candidate for Cushing’s disease. It might also serve as potential pharmacological tool for treating retina degenerative diseases and Alzheimer's disease.