December 17, 2012 -- LP-44, a highly potent, selective 5-HT7 agonist for unravelling neuronal functioning and neuropsychiatric disease
Abcam today announced signing a licence with the University of Bari to offer LP-44 – a novel, selectve 5-HT7 agonist. This life sciences tool, new to the Abcam Biochemicals range, is set to aid neuronal research into various neuropsychiatric diseases.
5-HT7 receptors are present in various regions of the central nervous system indicating a potential for therapeutic intervention in various neuropsychiatric diseases. Expression in brain regions (suprachiasmatic nuclei) involved in circadian rhythms may point to an involvement in sleep disorders. Many promising 5-HT7 compounds have failed to meet expectations of potency, selectivity and metabolic stability and few agonists have been reported. LP-44 and LP-12, identified from chemical screens, show high selectivity and potency for 5-HT7, at nanomolar concentrations in in vitro binding assays.
Steve Roome, Abcam Biochemical’s General Manager explains, “It is very exciting to finally see a selective 5-HT7 receptor agonist with the potential to enhance behaviour and circadian rhythm. The addition of these new selective tools really enhances the power of serotonin research in the field.”
LP-44 - Shows >200 and >1000-fold selectivity for 5-HT7 over 5-HT1A and 5-HT2A receptors (Ki values are 0.22, 52.7 and 326 nM respectively). Supresses REM sleep.
LP-12 - 5-HT7 agonist. Selective over D2, 5-HT1A and 5-HT2A receptors (Ki values are 0.13, 224, 60.9 and >1000 nM respectively). Shows pro-nociceptive effect.
References
Leopoldo M, et al. Structure-affinity relationship study on N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinealkylamides, a new class of 5-hydroxytryptamine7 receptor agents. J Med Chem 47(26):6616-24 (2004). Monti JM, et al. The serotonin 5-HT7 receptor agonist LP-44 microinjected into the dorsal raphe nucleus suppresses REM sleep in the rat. Behav Brain Res 191(2):184-9 (2008).
Xu Y, et al. Corticosterone induced morphological changes of hippocampal and amygdaloid cell lines are dependent on 5-HT7 receptor related signal pathway. Neuroscience 182:71-81 (2011).
About Abcam plc
Abcam is a producer and distributor of high quality protein research tools. These tools enable life scientists to analyse components of living cells at the molecular level, which is essential in understanding health and disease. Headquartered in Cambridge (UK), Abcam has subsidiary offices in Bristol (UK), Cambridge, MA (USA), Eugene, OR (USA), San Francisco, CA (USA), Tokyo (Japan), Hangzhou and Hong Kong (both in China), allowing it to serve a global customer base in over 130 countries. Abcam employs over 600 staff across its eight operating companies.
Abcam now has an online catalogue of over 100,000 products sourced from over 400 suppliers. The catalogue includes a growing range of non-primary antibody products such as secondaries, proteins, peptides, lysates, immunoassays and other kits. Products are available for life science research and distributed to academic and commercial users. A highly developed eCommerce platform, which includes regional websites for the Chinese and Japanese markets, allows customers to access up-to-date and detailed technical product data sheets at the Company’s website www.abcam.com
Abcam Biochemicals
Abcam Biochemicals is a range of exceptional quality and high performance biochemicals. The range includes high purity agonists, antagonists, channel blockers, enzyme inhibitors and signaling tools for life science researchers.
Contacts:
Dr Steve Roome
General Manager
Abcam Biochemicals
Phone: +44 (0)117 982 9988
steve.roome@abcam.co.uk
