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Novel selective β1-adrenoceptor antagonists for concomitant cardiovascular and respiratory disease (2017)
Journal Article
Baker, J. G., Gardiner, S. M., Woolard, J., Fromont, C., Jadhav, G. P., Mistry, S. N., …Fischer, P. M. (2017). Novel selective β1-adrenoceptor antagonists for concomitant cardiovascular and respiratory disease. FASEB Journal, 31(7), doi:10.1096/fj.201601305R. ISSN 0892-6638

β-Blockers reduce mortality and improve symptoms in people with heart disease. However, current clinically available β-blockers have poor selectivity for the cardiac β1-adrenoceptor (AR) over the lung β2-AR. Unwanted β2-blockade risks causing life-th... Read More

Salmeterol's extreme b2 selectivity is due to residues in both extracellular loops and transmembrane domains (2015)
Journal Article
Baker, J. G., Proudman, R. G., & Hill, S. J. (2015). Salmeterol's extreme b2 selectivity is due to residues in both extracellular loops and transmembrane domains. Molecular Pharmacology, 87(1), doi:10.1124/mol.114.095364. ISSN 0026-895X

Salmeterol is a long-acting b2-agonist, widely used as an inhaled treatment of asthma and chronic obstructive pulmonary disease. It has very high b2-affinity (log KD 28.95) and is very selective for the b2-adrenoceptor (1000-fold selectivity over the... Read More

Identification of key residues in transmembrane 4 responsible for the secondary, low-affinity conformation of the human 1-adrenoceptor (2014)
Journal Article
Baker, J. G., Proudman, R. G., & Hill, S. J. (2014). Identification of key residues in transmembrane 4 responsible for the secondary, low-affinity conformation of the human 1-adrenoceptor. Molecular Pharmacology, 85(5), doi:10.1124/mol.114.091587. ISSN 0026-895X

The β1-adrenoceptor exists in two agonist conformations/states: 1) a high-affinity state where responses to catecholamines and other agonists (e.g., cimaterol) are potently inhibited by β1-adrenoceptor antagonists, and 2) a low-affinity secondary con... Read More

Impact of polymorphic variants on the molecular pharmacology of the two-agonist conformations of the human β1-adrenoceptor (2013)
Journal Article
Baker, J. G., Hill, S. J., & Proudman, R. G. (2013). Impact of polymorphic variants on the molecular pharmacology of the two-agonist conformations of the human β1-adrenoceptor. PLoS ONE, 8(11), doi:10.1371/journal.pone.0077582. ISSN 1932-6203

β-blockers are widely used to improve symptoms and prolong life in heart disease primarily by inhibiting the actions of endogenous catecholamines at the β1-adrenoceptor. There are two common naturally occurring polymorphisms within the human β1-adren... Read More

Synthesis and in vitro and in vivo characterization of highly β1-Selective β-Adrenoceptor partial agonists (2013)
Journal Article
Mistry, S. N., Baker, J. G., Fischer, P. M., Hill, S. J., Gardiner, S. M., & Kellam, B. (2013). Synthesis and in vitro and in vivo characterization of highly β1-Selective β-Adrenoceptor partial agonists. Journal of Medicinal Chemistry, 56(10), doi:10.1021/jm400348g. ISSN 0022-2623

β-Adrenoceptor antagonists boast a 50-year use for symptomatic control in numerous cardiovascular diseases. One might expect highly selective antagonists are available for the human β-adrenoceptor subtype involved in these diseases, yet few truly β1-... Read More