birt-377 and Inflammation

birt-377 has been researched along with Inflammation* in 2 studies

Other Studies

2 other study(ies) available for birt-377 and Inflammation

Article	Year
De novo design, synthesis, and in vitro activity of LFA-1 antagonists based on a bicyclic[5.5]hydantoin scaffold. Bioorganic & medicinal chemistry letters, 2005, Feb-15, Volume: 15, Issue:4 LFA-1 (leukocyte function-associated antigen-1), is a member of the beta(2)-integrin family and is expressed on all leukocytes. The LFA-1/ICAM interaction promotes tight adhesion between activated leukocytes and the endothelium, as well as between T cells and antigen-presenting cells. Evidence from both animal models and clinical trials provides support for LFA-1 as a target in several different inflammatory diseases. This paper describes the de novo design, synthesis and in vitro activity of LFA-1 antagonists based on a bicyclic[5.5]hydantoin scaffold. Topics: Bridged Bicyclo Compounds, Heterocyclic; Drug Design; HeLa Cells; Humans; Hydantoins; Inflammation; Inhibitory Concentration 50; Intercellular Adhesion Molecule-1; Lymphocyte Function-Associated Antigen-1; Molecular Conformation; Protein Binding; Structure-Activity Relationship	2005
The role of leukocyte function-associated antigen-1 in animal models of inflammation. European journal of pharmacology, 2001, Oct-19, Volume: 429, Issue:1-3 Both preclinical and clinical data have identified leukocyte function-associated antigen-1 (LFA-1) as an important component of inflammatory disease states. We evaluated small molecule inhibitors of this glycoprotein in several animal models in which the inflammatory process is dependent on human or non-human primate LFA-1. (R)-5(4-bromobenzyl)-3(3,5-dichlorophenyl)-1,5-dimethylimidazolidine-2,4-dione, BIRT 377, effectively suppressed the production of human immunoglobulin (IgG) following reconstitution of severe combined immunodeficient (SCID) mice with human peripheral blood mononuclear cells. The BIRT 377 analog, BIX 642, inhibited the cellular infiltrate and increase in skin thickness associated with the delayed-type hypersensitivity reaction in previously immunized squirrel monkeys challenged with antigen. BIX 642 also inhibited the trans-vivo delayed-type hypersensitivity response in the footpads of SCID mice injected with human peripheral blood mononuclear cells and donor-sensitive antigen. These results demonstrate the efficacy of small molecule inhibitors of LFA-1 in preclinical models of inflammation dependent on human or non-human primate LFA-1. Topics: Animals; Disease Models, Animal; Humans; Hypersensitivity, Delayed; Imidazoles; Imidazolidines; Immunoglobulin G; Immunosuppressive Agents; Inflammation; Leukocytes, Mononuclear; Lymphocyte Function-Associated Antigen-1; Male; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, SCID; Saimiri	2001

Article

Year

De novo design, synthesis, and in vitro activity of LFA-1 antagonists based on a bicyclic[5.5]hydantoin scaffold.

Bioorganic & medicinal chemistry letters, 2005, Feb-15, Volume: 15, Issue:4

LFA-1 (leukocyte function-associated antigen-1), is a member of the beta(2)-integrin family and is expressed on all leukocytes. The LFA-1/ICAM interaction promotes tight adhesion between activated leukocytes and the endothelium, as well as between T cells and antigen-presenting cells. Evidence from both animal models and clinical trials provides support for LFA-1 as a target in several different inflammatory diseases. This paper describes the de novo design, synthesis and in vitro activity of LFA-1 antagonists based on a bicyclic[5.5]hydantoin scaffold.

Topics: Bridged Bicyclo Compounds, Heterocyclic; Drug Design; HeLa Cells; Humans; Hydantoins; Inflammation; Inhibitory Concentration 50; Intercellular Adhesion Molecule-1; Lymphocyte Function-Associated Antigen-1; Molecular Conformation; Protein Binding; Structure-Activity Relationship

2005

The role of leukocyte function-associated antigen-1 in animal models of inflammation.

European journal of pharmacology, 2001, Oct-19, Volume: 429, Issue:1-3

Both preclinical and clinical data have identified leukocyte function-associated antigen-1 (LFA-1) as an important component of inflammatory disease states. We evaluated small molecule inhibitors of this glycoprotein in several animal models in which the inflammatory process is dependent on human or non-human primate LFA-1. (R)-5(4-bromobenzyl)-3(3,5-dichlorophenyl)-1,5-dimethylimidazolidine-2,4-dione, BIRT 377, effectively suppressed the production of human immunoglobulin (IgG) following reconstitution of severe combined immunodeficient (SCID) mice with human peripheral blood mononuclear cells. The BIRT 377 analog, BIX 642, inhibited the cellular infiltrate and increase in skin thickness associated with the delayed-type hypersensitivity reaction in previously immunized squirrel monkeys challenged with antigen. BIX 642 also inhibited the trans-vivo delayed-type hypersensitivity response in the footpads of SCID mice injected with human peripheral blood mononuclear cells and donor-sensitive antigen. These results demonstrate the efficacy of small molecule inhibitors of LFA-1 in preclinical models of inflammation dependent on human or non-human primate LFA-1.

Topics: Animals; Disease Models, Animal; Humans; Hypersensitivity, Delayed; Imidazoles; Imidazolidines; Immunoglobulin G; Immunosuppressive Agents; Inflammation; Leukocytes, Mononuclear; Lymphocyte Function-Associated Antigen-1; Male; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, SCID; Saimiri

2001