Matches in SemOpenAlex for { <https://semopenalex.org/work/W2943505387> ?p ?o ?g. }
- W2943505387 endingPage "2003" @default.
- W2943505387 startingPage "1989" @default.
- W2943505387 abstract "Abstract P2X4 is a ligand-gated ion channel implicated in neuropathic pain. Drug discovery efforts targeting P2X4 have been unsuccessful largely because of the difficulty in engineering specificity and selectivity. Here, we describe for the first time the generation of a panel of diverse monoclonal antibodies (mAbs) to human and mouse P2X4, capable of both positive and negative modulation of channel function. The affinity-optimised anti-P2X4 mAb IgG#151-LO showed exquisite selectivity for human P2X4 and induced potent and complete block of P2X4 currents. Site-directed mutagenesis of P2X4 revealed the head domain as a key interaction site for inhibitory mAbs. Inhibition of spinal P2X4 either by intrathecal delivery of an anti-P2X4 mAb or by systemic delivery of an anti-P2X4 bispecific mAb with enhanced blood–spinal cord barrier permeability produced long-lasting (>7 days) analgesia in a mouse model of neuropathic pain. We therefore propose that inhibitory mAbs binding the head domain of P2X4 have therapeutic potential for the treatment of neuropathic pain." @default.
- W2943505387 created "2019-05-09" @default.
- W2943505387 creator A5005026100 @default.
- W2943505387 creator A5009100559 @default.
- W2943505387 creator A5014196259 @default.
- W2943505387 creator A5015060303 @default.
- W2943505387 creator A5016387491 @default.
- W2943505387 creator A5022557754 @default.
- W2943505387 creator A5024250677 @default.
- W2943505387 creator A5026721816 @default.
- W2943505387 creator A5033240222 @default.
- W2943505387 creator A5033732082 @default.
- W2943505387 creator A5036338186 @default.
- W2943505387 creator A5043770791 @default.
- W2943505387 creator A5047707308 @default.
- W2943505387 creator A5051099517 @default.
- W2943505387 creator A5064096764 @default.
- W2943505387 creator A5070176713 @default.
- W2943505387 creator A5074439039 @default.
- W2943505387 creator A5074922773 @default.
- W2943505387 creator A5075121122 @default.
- W2943505387 creator A5080629319 @default.
- W2943505387 creator A5082386427 @default.
- W2943505387 creator A5082949148 @default.
- W2943505387 date "2019-04-24" @default.
- W2943505387 modified "2023-10-14" @default.
- W2943505387 title "Antibodies binding the head domain of P2X4 inhibit channel function and reverse neuropathic pain" @default.
- W2943505387 cites W1485730287 @default.
- W2943505387 cites W1490568823 @default.
- W2943505387 cites W1555062540 @default.
- W2943505387 cites W1587106102 @default.
- W2943505387 cites W1601321038 @default.
- W2943505387 cites W1782255760 @default.
- W2943505387 cites W1826475137 @default.
- W2943505387 cites W1964053427 @default.
- W2943505387 cites W1972529974 @default.
- W2943505387 cites W1974003058 @default.
- W2943505387 cites W1984025105 @default.
- W2943505387 cites W1985748128 @default.
- W2943505387 cites W1991831286 @default.
- W2943505387 cites W1997865085 @default.
- W2943505387 cites W1999613945 @default.
- W2943505387 cites W1999700891 @default.
- W2943505387 cites W2004017460 @default.
- W2943505387 cites W2004111769 @default.
- W2943505387 cites W2005137753 @default.
- W2943505387 cites W2006174330 @default.
- W2943505387 cites W2007626882 @default.
- W2943505387 cites W2010754951 @default.
- W2943505387 cites W2011005824 @default.
- W2943505387 cites W2012649101 @default.
- W2943505387 cites W2016904568 @default.
- W2943505387 cites W2023490488 @default.
- W2943505387 cites W2027236524 @default.
- W2943505387 cites W2028489386 @default.
- W2943505387 cites W2028561217 @default.
- W2943505387 cites W2030131290 @default.
- W2943505387 cites W2032252553 @default.
- W2943505387 cites W2032901225 @default.
- W2943505387 cites W2035258850 @default.
- W2943505387 cites W2036013134 @default.
- W2943505387 cites W2039870425 @default.
- W2943505387 cites W2040545420 @default.
- W2943505387 cites W2054643756 @default.
- W2943505387 cites W2065283382 @default.
- W2943505387 cites W2067924690 @default.
- W2943505387 cites W2074339161 @default.
- W2943505387 cites W2078336096 @default.
- W2943505387 cites W2090527768 @default.
- W2943505387 cites W2092118947 @default.
- W2943505387 cites W2092307090 @default.
- W2943505387 cites W2095795382 @default.
- W2943505387 cites W2099163813 @default.
- W2943505387 cites W2104017463 @default.
- W2943505387 cites W2104818454 @default.
- W2943505387 cites W2105711740 @default.
- W2943505387 cites W2120143347 @default.
- W2943505387 cites W2123562124 @default.
- W2943505387 cites W2125421971 @default.
- W2943505387 cites W2133712572 @default.
- W2943505387 cites W2138227733 @default.
- W2943505387 cites W2166805374 @default.
- W2943505387 cites W2196308323 @default.
- W2943505387 cites W2232251872 @default.
- W2943505387 cites W2255446000 @default.
- W2943505387 cites W2280595927 @default.
- W2943505387 cites W2340170655 @default.
- W2943505387 cites W2344980370 @default.
- W2943505387 cites W2508001580 @default.
- W2943505387 cites W2513150856 @default.
- W2943505387 cites W2519597790 @default.
- W2943505387 cites W2549185398 @default.
- W2943505387 cites W2550534389 @default.
- W2943505387 cites W2559826741 @default.
- W2943505387 cites W2586627217 @default.
- W2943505387 cites W2601937854 @default.
- W2943505387 cites W2606721249 @default.
- W2943505387 cites W2767041448 @default.