New biologically active molecules in milligram quantities

The sigma-1 receptor is a transmembrane protein expressed in many different tissue types. It is particularly concentrated in certain regions of the central nervous system. It has been implicated in myriad phenomena, including cardiovascular function, schizophrenia, clinical depression, the effects of cocaine abuse, and cancer. Much is known about the binding affinity of hundreds of synthetic compounds to the sigma-1 receptor.

The alpha-7 nicotinic receptor, also known as the α7 receptor, is a type of nicotinic acetylcholine receptor, consisting entirely of α7 subunits. Recent work has demonstrated its potential role in reducing inflammatory neurotoxicity in stroke, MI, sepsis, and Alzheimer's disease.

Acetyl-CoA acetyltransferase is an enzyme that in humans is encoded by the ACAT1 (Acetyl-Coenzyme A acetyltransferase 1) gene. Defects in this gene are associated with 3-ketothiolase deficiency, an inborn error of isoleucine catabolism characterized by urinary excretion of 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, tiglylglycine, and butanone.

Janus kinase 3 is a tyrosine kinase that belongs to the Janus family of kinases. Activating mutations in JAK1, JAK2, and JAK3 have been identified as causes of hematological cancers, while inactivating mutations of JAK3 are known causes of immune deficiency.

References:

1. B. Wünsch.  The σ1 Receptor Antagonist S1RA Is a Promising Candidate for the Treatment of Neurogenic Pain.  J. Med. Chem. (2012), 55, 8209-8210
2. Faghih et al. Discovery of 4-(5-(4-Chlorophenyl)-2-methyl-3-propionyl-1H-pyrrol-1-yl)benzenesulfonamide (A-867744) as a Novel Positive Allosteric Modulator of the r7 Nicotinic Acetylcholine Receptor. J. Med. Chem. (2009), 52, 3377–3384
3. Ikenoya et al. A selective ACAT-1 inhibitor, K-604, suppresses fatty streak lesions in fat-fed hamsters without affecting plasma cholesterol levels. Atherosclerosis 191 (2007) 290–297
4. Thoma et al. Identification of a potent Janus kinase 3 inhibitor with high selectivity within the Janus kinase family. J. Med. Chem. (2010), 54, 284