id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-006104-f9000hjy	Morgan, B. Paul	Complement, a target for therapy in inflammatory and degenerative diseases	2015-10-23		.txt	text/plain	16338	695	37	Complement provides numerous options for drug development as it is a proteolytic cascade that involves nine specific proteases, unique multimolecular activation and lytic complexes, an arsenal of natural inhibitors, and numerous receptors that bind to activation fragments. The wealth of structural information now available in the field, including snapshots of convertase enzymes and MAC precursor complexes captured in active conformations, unmasks the precise nature of these protein-protein interactions and identifies sites that are key to the interaction that can be targeted with small molecules or biologicals using structure-based drug design 43, 44 . In vitro studies more than 35 years ago showed that modest (around 10% above baseline) increases in the concentrations of the complement regulators FH and FI markedly reduced plasma alternative-pathway activity, provoking the suggestion that augmentation of these proteins might be of therapeutic benefit 74 ; however, large (and probably frequent) doses will be required to substantially alter the levels of these abundant proteins. Design and development of TT30, a novel C3d targeted C3/C5 convertase inhibitor for treatment of human complement alternative pathway-mediated diseases	./cache/cord-006104-f9000hjy.txt	./txt/cord-006104-f9000hjy.txt