Identification of a non peptidic RANTES antagonist.
A series of phenothiazines demonstrating inhibition of RANTES binding to THP-1 cell membranes has been identified. The lead compound RP23618 (IC50 = 3 microM) was found to inhibit specific binding of 125I-RANTES, but not 125I-MCP-1 to THP-1 cell membranes and furthermore to antagonize RANTES, but not MCP-1-induced chemotaxis of THP-1 cells.
Bright
C
C
Rhône-Poulenc Rorer, Dagenham Research Centre, Dagenham, Essex, UK.
Brown
T J
TJ
Cox
P
P
Halley
F
F
Lockey
P
P
McLay
I M
IM
Moore
U
U
Porter
B
B
Williams
R J
RJ
D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors*; D015195:Drug Design; D006801:Humans; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D007700:Kinetics; D015394:Molecular Structure; D010640:Phenothiazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D018932:Chemokine CCL2; D018946:Chemokine CCL5; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D010640:Phenothiazines; C116623:RP 23618