June 2008 Drug Protein Targets
amine oxidase (flavin containing) domain 2
This nuclear protein, also known as AOF2, is a component of several histone deacetylase complexes. It is also a histone demethylase activity (it demethylates the 'Lys-4' of histone H3) and this is believed to be responsible for an ability to silence genes. Research suggests that inhibition of AOF2 can reactivate genes normally suppressed during cancer.
- Progen is developing compounds that inhibit AOF2 as anticancers, they are part of Progen's epigenetics programme.
- AOF2 belongs to the Enzyme Target Family Group and its EC number is 1.4.3.4. Its Entrez Gene ID is 23028.
keratin 6A
More commonly known as KRT6A this type II cytokeratin is the most abundant isoform of keratin 6. It is present in the epithelial lining of oral mucosa, oesophagus, hair follicules, palm and sole epidermis, epithelial cells of the nail bed and the filiform papillae of the tongue. Mutations in KRT6A are known to lead to pachyonychia congenital type 1.
- TD-101 is a short interfering RNA (siRNA) specific for the N171K point mutation in the keratin 6A gene, under develpment by TransDerm for the treatment of pachyonychia congenita.
- Its Entrez Gene ID is 3853.
glutamate receptor, metabotropic 7
Glutamate receptor, metabotropic 7 (GRM7) belongs to the Group III family of metobotropicglutamate recptors which are known to be linked to inhibition of the cyclic AMP cascade. It is expressed in many areas of the brain and may act presynaptically to regulate neurotransmission in the hippocampus and play a role in learning and memory.
- Addex is developing GRM7 negative allosteric modulators (NAM) for the treatment of depression and post-traumatic stress syndrome.
- MGLUR7 belongs to the Receptor>GPCR>Metabotropic glutamte Target Family Groups. Its Entrez Gene ID is 2917.
klotho beta
Klotho beta (KLB) is a member of the glycosidase I superfamily. It is expressed in the liver, pancreas and adipose tissue and is thought to negatively regulate bile acid synthesis through mediating the interaction of fibroblast growth factor (FGF)- 15 with FRG receptor 4. Research has also suggested a role in lipid metabolism as a cofactor for the interaction of FGF-21 with FGF Receptor 1c in adipocytes.
- Amgen is developing recombinant FGF-21 which activates FGF receptor tyrosine kinase and beta klotho for the treatment of obesity, steatohepatitis and insulin resistance.
- Klotho beta belongs to the Enzyme Target Family Group. Its Entrez Gene ID is 152831.
Pharmaprojects - New protein targets for drug development
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