Identification of a non peptidic RANTES antagonist

C Bright; T J Brown; P Cox; F Halley; P Lockey; I M McLay; U Moore; B Porter; R J Williams

doi:10.1016/s0960-894x(98)00094-8

Identification of a non peptidic RANTES antagonist

Bioorg Med Chem Lett. 1998 Apr 7;8(7):771-4. doi: 10.1016/s0960-894x(98)00094-8.

Authors

C Bright¹, T J Brown, P Cox, F Halley, P Lockey, I M McLay, U Moore, B Porter, R J Williams

Affiliation

¹ Rhône-Poulenc Rorer, Dagenham Research Centre, Dagenham, Essex, UK.

PMID: 9871539
DOI: 10.1016/s0960-894x(98)00094-8

Abstract

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.

MeSH terms

Cell Membrane / drug effects
Cell Membrane / metabolism
Chemokine CCL2 / metabolism
Chemokine CCL5 / antagonists & inhibitors*
Drug Design
Humans
Indicators and Reagents
Iodine Radioisotopes
Kinetics
Molecular Structure
Phenothiazines / chemical synthesis
Phenothiazines / chemistry
Phenothiazines / pharmacology*
Structure-Activity Relationship
Tumor Cells, Cultured

Substances

Chemokine CCL2
Chemokine CCL5
Indicators and Reagents
Iodine Radioisotopes
Phenothiazines
RP 23618