AMG-837 is an orally bioavailable partial agonist of the GPR40 (EC50 value 13.5 nM for AMG 837 stimulated Ca2 flux in CHO cells expressing human GPR40) with a superior pharmacokinetic profile. AMG837 stimulated robust glucose-dependent insulin secretion (EC50 value 142±20 nM) in isolated rodent islets, and lowered post-prandial glucose in normal rats. Acute administration of AMG-837 lowered glucose excursions and increased glucose stimulated insulin secretion during glucose tolerance tests in both normal and Zucker fatty rats. The improvement in glucose excursions persisted following daily dosing of AMG 837 for 21-days in Zucker fatty rats. Preclinical studies demonstrated that AMG-837 was a potent GPR40 partial agonist which lowered post-prandial glucose levels. AMG-837 exhibits a potential utility for the treatment of type 2 diabetes. Amgen removed AMG-837 from Phase I clinical trials due to concerns over toxicity.

Corydaline is a pharmacologically active isoquinoline alkaloid isolated from Corydalis tubers. It exhibits the antiacetylcholinesterase, antiallergic, antinociceptive, and gastric emptying activities. Corydaline exhibited strong nematocidal activity, showed little cytotoxicity and represents a potential treatment for Strongyloidiasis. Corydaline exhibits gastrointestinal modulatory, antinociceptive, anti-allergic, and anti-parasitic activities. Corydaline is currently in clinical trials as a potential treatment for functional dyspepsia. In animal models, corydaline increases gastric emptying and small intestine transit speed and induces gastric relaxation. In other animal models, corydaline inhibits chemically-induced pain. Additionally, this compound may inhibit mast cell-dependent smooth muscle contraction of the aorta. Corydaline also exhibits nematocidal activity against species of Strongyloides.

Corydaline is a pharmacologically active isoquinoline alkaloid isolated from Corydalis tubers. It exhibits the antiacetylcholinesterase, antiallergic, antinociceptive, and gastric emptying activities. Corydaline exhibited strong nematocidal activity, showed little cytotoxicity and represents a potential treatment for Strongyloidiasis. Corydaline exhibits gastrointestinal modulatory, antinociceptive, anti-allergic, and anti-parasitic activities. Corydaline is currently in clinical trials as a potential treatment for functional dyspepsia. In animal models, corydaline increases gastric emptying and small intestine transit speed and induces gastric relaxation. In other animal models, corydaline inhibits chemically-induced pain. Additionally, this compound may inhibit mast cell-dependent smooth muscle contraction of the aorta. Corydaline also exhibits nematocidal activity against species of Strongyloides.

Levovirin is a guanosine nucleoside analog and the L-enantiomer of ribavirin. It is an investigational drug for the treatment of hepatitis C virus-mediated diseases. Levovirin has a similar immunomodulatory potency to ribavirin in vitro without accumulating in red blood cells or causing hemolytic anemia, a known side effect of ribavirin. Levovirin has been shown to stimulate host immune responses (enhanced Th1 and reduced Th2 cytokine expression). Significantly improved oral absorption of levovirin was achieved following administration of a valine ester prodrug of levovirin R1518. Levovirin was found more potent to inhibit Tick-borne encephalitis virus (TBEV) on the basis of robust binding affinity between protein-drug interactions. This finding may help to understand the nature of helicase and development of specific anti-TBEV therapies.

(R)-Bambuterol is a selective β2-adrenoceptor agonist. R-Bambuterol Hydrochloride Tablets ("Laevo-Bambuterol") is categorized as a Class 1 new drug. Its preclinical studies show that it is more effective and have lower toxicity than Bambuterol, a popular asthma drug currenTLy on the market. Laevo-Bambuterol was approved by the China Food and Drug Administration for the treatment of asthma.

XK-469 (NSC 697887) is a synthetic quinoxaline phenoxypropionic acid derivative that possesses unusual solid tumor selectivity and activity against multidrug-resistant cancer cells. XK469 acts as a selective topoisomerase IIβ inhibitor. Other proposed mechanisms include XK469-induced inhibition of cyclin B1 ubiquitination and apoptosis via binding of the peripheral benzodiazepine receptor. A phase I study was performed to determine the safety and pharmacokinetics of XK469R in patients with various neoplasms.

SB-271046 is one of the first selective 5-HT6 receptor antagonists to be discovered. SB-271046 is a potent, selective and orally active 5-HT6 receptor antagonist with a pKi value of 8.9. This compound provides a useful tool for further elucidating the physiological function of 5-HT6 receptors in vivo. SB-271046 was found to increase levels of the excitatory amino acid neurotransmitters glutamate and aspartate, as well as dopamine and noradrenaline in the frontal cortex and hippocampus of rats, and 5-HT6 antagonists have been shown to produce nootropic effects in a variety of animal studies. Suggested applications of SB-271046 included treatment of schizophrenia and other psychiatric disorders. A phase I clinical development of SB-271046 by GlaxoSmithKline (GSK) was discontinued due to a poor BBB permeability.

McN-5652 is one of a series of substituted pyrrolo-isoquinolines that, as a group, potently inhibit the uptake of one or more of the monoamines, norepinephrine, serotonin and dopamine. Receptor binding experiments indicated that McN-5652 has a weak affinity for serotonin 5-HT2 and alpha-1 adrenergic receptors. Abnormalities of the 5-HT transporter have been suggested in mood disorders, since it is one of the major binding sites of antidepressants. (+)-[11C]McN 5652 is an appropriate radiotracer to quantify 5-HT transporters in regions with relatively high concentration of 5-HT transporters, such as the midbrain, thalamus, and basal ganglia, and should prove useful in elucidating abnormalities of 5-HT transmission in neuropsychiatric conditions.

WAY-181187 is a high affinity and selective 5-HT6 agonist. It displays 60-fold selectivity over other 5-HT and monoamine receptors. WAY-181187 stimulates cAMP, ERK1/2 and Fyn kinase signaling pathway through serotonin receptor activation. WAY-181187 produced both antidepressant-like and anxiolytic-like effects in the animal model. It had been in phase I clinical trial for the treatment of anxiety disorders but this research has been discontinued.

L-822179 is a triazolophthalazine that selectively attenuates the effects of GABA at GABA(A) receptors containing an alpha5 subunit. It is an orally active, functionally selective compound, which enhances cognition in animals without anxiogenic or convulsant effects. The dose-limiting adverse event of L-822179 is dizziness and/or light-headedness. L-822179 does not improve cognitive performance in the elderly; indeed the dose of 4 mg actually significantly impairs performance. In this regard, it could therefore be considered that this study is a failed trial in so far as the positive control, lorazepam, does not show the anticipated effect.