MK-912 is non-specific alpha-2 adrenergic receptor antagonist, with high affinity for the alpha-2-A, alpha-2B, and alpha-2C variants. Originally developed by Merk & Co, it has been investigated for potential therapeutic properties for the treatment of depression and diabetes. MK-912 is also regularly used as a molecular probe in biomedical studies seeking information about alpha-2 adrenergic receptors.

D-Galacturonic acid is the main constituent of pectin, a naturally abundant compound. It is the monobasic acid resulting from oxidation of the primary alcohol group of D-galactose to carboxyl. D-Galacturonic acid prepared from pectin can be used to synthesize vitamin C. Native pectin is a mixture of polysaccharides, with the major component a polymer of -D-galacturonic acid. Pectin has numerous other medical and pharmaceutical uses, for example in combination with plant hemicelluloses and lignin, may be useful dietary constituents in preventing coronary heart disease, diverticular disease, ulcerative colitis, and a variety of other Western diseases. Pectin, a representative diety fibre, is a gelatinous substance derived from the cell walls of fruits and some plants and contains galacturonan, consisting of mostly long-chain D-galacturonic acids combined into units by α-1,4 linkages. As a kind of soluble dietary fiber, pectin has been proved of controlling glucose and blood lipids. It slows rapid infusion of the liquid meal into the gut by delaying gastric emptying.

PRT062607 (BIIB-057; P 50515 PRT-2607; PRT062607) is a highly specific and potent inhibitor of spleen tyrosine kinase (Syk). PRT062607 (BIIB-057) has a desirable pharmacokinetics profile and is capable of safely, potently, and selectively suppressing SYK kinase function in humans following once-daily oral dosing. The compound is being evaluated for the treatment of chronic inflammatory diseases; including rheumatoid arthritis, systemic lupus erythematosus, non-Hodgkin's lymphoma and chronic lymphocytic leukaemia. Phase I development is underway in the US and the UK for the treatment of patients with inflammation and cancer. Phase I development is also being conducted in rheumatoid arthritis and systemic lupus erythematosus, presumably in the US.

Ellipticine (5,11-dimethyl-6H-pyrido[4,3-b]carbazole), an alkaloid isolated from Apocyanaceae plants (i.e. Ochrosia borbonica, Excavatia coccinea), and several its derivatives exhibit significant antitumor and anti-HIV activities. This compound is one of the simplest naturally occurring alkaloids, having a planar structure. It was first isolated in 1959 from the leaves of the evergreen tree Ochrosia elliptica, which grows wild in Oceania. Ellipticine and its more soluble derivatives (9-hydroxyellipticine, 9-hydroxy-N2-methylellipticinium, 9-chloro-N2 -methylellipticinium and 9-methoxy-N2 -methylellipticinium) exhibit promising results for the treatment of osteolytic breast cancer metastases, kidney cancer, brain tumors and acute myeloblastic leukemia. The main reason for the interest in ellipticine and its derivatives for clinical purposes is their high efficiencies against several types of cancer, their rather limited toxic side effects and their complete lack of hematological toxicity. Nevertheless, the mutagenicity of ellipticines should be evaluated as a potential risk factor for these anticancer agents. Most ellipticines are mutagenic to Salmonella typhimurium Ames tester strains, bacteriophage T4, Neurospora crassa, and mammalian cells and induce prophage lambda in Escherichia coli. The anti-tumor therapeutic ellipticine and its derivatives act as potent anticancer agents via a combined mechanism involving cell cycle arrest and induction of apoptosis. Cell death induced by ellipticine has been shown to engage a p53-dependent pathway, cell cycle arrest, interaction with several kinases and induction of the mitochondrial pathway of apoptotic cell death. Cell cycle arrest was shown to result from DNA damage caused by a variety of tumor chemotherapeutic agents; this is also the case for ellipticines. The prevalent DNA-mediated mechanisms of anti-tumor, mutagenic and cytotoxic activities of ellipticine are (i) intercalation into DNA, (ii) inhibition of DNA topoisomerase II activity, and (iii) covalent binding to DNA in vitro and in vivo after enzymatic activation by cytochrome P450 and/or peroxidase enzymes The mechanism leading to apoptosis by ellipticine is thought to also be associated with DNA damage, by inhibition of topoisomerase II and the covalent modification of DNA. In addition, the formation of ellipticine-DNA adducts ultimately can mutate cancer cells or initiate cell death.

Y-33075 is potent and selective ROCK (Rho-associated coiled-coil-forming protein kinase) inhibitor, developed by Yoshitomi Pharmaceutical Industries for encephalomyelitis treatment. In rabbits and in monkeys, Y-33075 lowers IOP in a dose-dependent fashion. An increase in regenerating axons of RGCs in 100 mM Y-33075-treated eyes is observed compared with saline-treated eyes. Y-33075 dose-dependently increases the number of RGCs with regenerating axons. Both Y-33075 induces a concentration-dependent relaxation in rabbit ciliary arteries precontracted with a high-potassium (high-K) solution. The amplitude of relaxation induced by Y-33075 is not affected by either 100 μM N (G)-nitro-L: -arginine methyl ester (L: -NAME) or 10 μM indomethacin. In Ca2 -free solution, Y-27632 and Y-39983 significantly inhibit the transient contraction of ciliary arteries induced by 10 μM histamine. However, neither Y-27632 nor Y-39983 affects the elevation of [Ca2 ](i) induced by high-K solution and histamine.

FK-960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel putative anti-dementia drug of piperazine derivative, ameliorates memory deficits in a variety of animal models of dementia in rats and monkeys, and also augments long-term potentiation (LTP) in the mossy fiber-CA3 pathway in guinea-pig hippocampal slices. FK-960 acts as Serotonin modulator. FK-960 had been in phase II clinical trials by Fujisawa Pharmaceutical (now Astellas) for the treatment of Alzheimer's disease (AD). However this study was suspended. In 2003 Phase-II for Alzheimer's disease in USA was discontinued and in Jul 2004 - Phase-II for Cognition disorders in Europe.

The investigational psychopharmacologic drug candidate CP 615003 (NGD 91-3) is a potent subtype-selective partial agonist at the GABA-A receptor complex. It was designed to be fast acting without causing the sedation, memory impairment, addiction or potentiation of effects of alcohol associated with conventional anti-anxiety medication. Tissue distribution studies conducted during early clinical development of CP 615003 suggested limited brain penetration. In the Phase II clinical study, subjects tested at the high dose of NGD 91-3 showed a trend toward efficacy that did not achieve statistical significance.

SB-743921 is a synthetic small molecule with potential antineoplastic properties. SB-743921 selectively inhibits the ATP-binding domain of the kinesin spindle protein (KSP), an important protein involved in the early stages of mitosis that is expressed in proliferating cells. Inhibition of KSP results in inhibition of mitotic spindle assembly and interrupts cell division, thereby causing cell cycle arrest and induction of apoptosis. SB-743921 has greater than 40,000 fold selectivity for KSP over other kinesins. SB-743921 has demonstrated promising anti-cancer activity in a variety of in vivo and in vitro human cancer models in preclinical studies. Furthermore, anti-cancer effect has been demonstrated in taxane-refractory malignancies with SB-743921. Toxicity studies demonstrated predictable neutropenias and gastrointestinal toxicities without clear evidence of neurotoxicity. The recommended phase II dose for SB-743921 as a 1-h infusion every 21 days is 4 mg/m2.

The selective serotonin reuptake inhibitor fluoxetine consists of equal amounts of R and S stereoisomers (antidepressant Prozac (racemic fluoxetine). Binding to the transporter confirmed selectivity of R- and S-fluoxetine for the 5-HT transporter versus the dopamine (DA) and norepinephrine (NE) human transporters. In addition, receptor binding studies demonstrated significant affinity of R-fluoxetine, but not S-fluoxetine, for human 5-HT(2A) and 5-HT(2C) receptor subtypes. R-fluoxetine acts as an antagonist at 5-HT(2A) and 5-HT(2C) receptors. The attempt to develop a single-enantiomer formulation of fluoxetine for the treatment of depression was unsuccessful. Eli Lilly has terminated its licensing and development agreement with Marlborough, Mass.-based Sepracor for (R)-fluoxetine, the single-isomer version of Lilly's antidepressant Prozac.R-enantiomer of fluoxetine, at its highest administered dose, led to statistically significant prolongation of cardiac repolarization in phase II studies; the studies were subsequently stopped.

PNU-142633 is selective 5HT1D partial agonist, developed by Pharmacia & Upjohn, Inc. It failed in phase II clinical trials against acute migraine, and its development was discontinued.