Gunnels Wood Road
Gunnels Wood Road
Brown J.R.,Glaxosmithkline |
Magid-Slav M.,709 Swedeland Road |
Sanseau P.,Gunnels Wood Road |
Rajpal D.K.,Moore Research
Drug Discovery Today | Year: 2011
The proliferation of genomic platform data, ranging from silencing RNAs through mRNA and microRNA expression to proteomics, is providing new insights into the interplay between human and pathogen genes during infection: the so-called 'host-pathogen interactome'. Exploiting the interactome for novel human drug targets could provide new therapeutic avenues towards the treatment of infectious disease, which could ameliorate the growing clinical challenge of drug-resistant infections. Using the hepatitis C virus interactome as an example, here we suggest a computational biology framework for identifying and prioritizing potential human host targets against infectious diseases. © 2011 Elsevier Ltd. All rights reserved.
Procopiou P.A.,Gunnels Wood Road |
Browning C.,Respiratory Biology |
Buckley J.M.,Gunnels Wood Road |
Clark K.L.,Respiratory Biology |
And 14 more authors.
Journal of Medicinal Chemistry | Year: 2011
A series of potent phthalazinone-based human H1 and H 3 bivalent histamine receptor antagonists, suitable for intranasal administration for the potential treatment of allergic rhinitis, were identified. Blockade of H3 receptors is thought to improve efficacy on nasal congestion, a symptom of allergic rhinitis that is currently not treated by current antihistamines. Two analogues (56a and 56b) had slightly lower H1 potency (pA2 9.1 and 8.9, respectively, vs 9.7 for the clinical gold-standard azelastine, and H3 potency (pK i 9.6 and 9.5, respectively, vs 6.8 for azelastine). Compound 56a had longer duration of action than azelastine, low brain penetration, and low oral bioavailability, which coupled with the predicted low clinical dose, should limit the potential of engaging CNS-related side-effects associated with H 1 or H3 antagonism. © 2011 American Chemical Society.