Gopinadhan N. Anilkumar
Schering-Plough
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Publication
Featured researches published by Gopinadhan N. Anilkumar.
Journal of Inflammation | 2009
Yuanfan Wang; Long Cui; Waldemar Gonsiorek; Soo-Hong Min; Gopinadhan N. Anilkumar; Stuart B. Rosenblum; Joseph A. Kozlowski; Daniel Lundell; Jay S. Fine; Ethan P. Grant
BackgroundCCR2 plays a key role in regulating monocyte trafficking to sites of inflammation and therefore has been the focus of much interest as a target for inflammatory disease.MethodsHere we examined the effects of CCR2 blockade with a potent small molecule antagonist to determine the pharmacodynamic consequences on the peripheral blood monocyte compartment in the context of acute and chronic inflammatory processes.ResultsWe demonstrate that CCR2 antagonism in vivo led to a rapid decrease in the number of circulating Ly6Chi monocytes and that this decrease was largely due to the CXCR4-dependent sequestration of these cells in the bone marrow, providing pharmacological evidence for a mechanism by which monocyte dynamics are regulated in vivo. CCR2 antagonism led to an accumulation of circulating CCL2 and CCL7 levels in the blood, indicating a role for CCR2 in regulating the levels of its ligands under homeostatic conditions. Finally, we show that the pharmacodynamic changes due to CCR2 antagonism were apparent after chronic dosing in mouse experimental autoimmune encephalomyelitis, a model in which CCR2 blockade demonstrated a dramatic reduction in disease severity, manifest in a reduced accumulation of monocytes and other cells in the CNS.ConclusionCCR2 antagonism in vivo has tractable pharmacodynamic effects that can be used to align target engagement with biologic effects on disease activity.
Biochemical and Biophysical Research Communications | 2010
Soo-Hong Min; Yuanfan Wang; Waldemar Gonsiorek; Gopinadhan N. Anilkumar; Joseph A. Kozlowski; Daniel Lundell; Jay S. Fine; Ethan P. Grant
Neutrophils and monocytes are abundantly represented in the synovial fluid and tissue in rheumatoid arthritis patients. We therefore explored the effects of small molecule chemokine receptor antagonists to block migration of these cells in anti-collagen antibody-induced arthritis. Targeting neutrophil migration with the CXCR2/CXCR1 antagonist SCH563705 led to a dose-dependent decrease in clinical disease scores and paw thickness measurements and clearly reduced inflammation and bone and cartilage degradation based on histopathology and paw cytokine analyses. In contrast, targeting monocyte migration with the CCR2 antagonist MK0812 had no effect on arthritis disease severity. The pharmacodynamic activities of both SCH563705 and MK0812 were verified by assessing their effects on the peripheral blood monocyte and neutrophil populations. SCH563705 selectively reduced the peripheral blood neutrophil frequency, and caused an elevation in the CXCR2 ligand CXCL1. MK0812 selectively reduced the peripheral blood monocyte frequency, and caused an elevation in the CCR2 ligand CCL2. The much greater impact of CXCR2/CXCR1 antagonism relative to CCR2 antagonism in this model of arthritis highlights the therapeutic potential for targeting CXCR2/CXCR1 in human arthritides.
Bioorganic & Medicinal Chemistry Letters | 2009
Brian F. Mcguinness; Carolyn DiIanni Carroll; Lisa Guise Zawacki; Guizhen Dong; Cangming Yang; Doug W. Hobbs; Biji Jacob-Samuel; James W. Hall; Chung-Her Jenh; Joseph A. Kozlowski; Gopinadhan N. Anilkumar; Stuart B. Rosenblum
High-throughput screening of an encoded combinatorial aryl piperazine library led to the identification of a novel series of potent piperazinyl-piperidine based CXCR3 antagonists. Analogs of the initial hit were synthesized via solid and solution phase methods to probe the influence of structure on the CXCR3 binding of these molecules. Various functional groups were found to contribute to the overall potency and essential molecular features were identified.
Archive | 2006
Brian F. Mcguinness; Stuart B. Rosenblum; Joseph A. Kozlowski; Gopinadhan N. Anilkumar; Seong Heon Kim; Neng-Yang Shih; Chung-Her Jenh; Paul J. Zavodny; Douglas W. Hobbs; Guizhen Dong; Yuefei Shao; Lisa Guise Zawacki; Changmeng Yang; Carolyn Dilanni Carroll
Archive | 2006
Gopinadhan N. Anilkumar; Qingbei Zeng; Stuart B. Rosenblum; Joseph A. Kozlowski; Brian F. Mcguinness; Douglas W. Hobbs
Archive | 2006
Seong Heon Kim; Gopinadhan N. Anilkumar; Michael K. C. Wong; Qingbei Zeng; Stuart B. Rosenblum; Joseph A. Kozlowski; Yuefei Shao; Brian F. Mcguinness; Douglas W. Hobbs
Archive | 2006
Wensheng Yu; Seong Heon Kim; Gopinadhan N. Anilkumar; Stuart B. Rosenblum; Bandarpalle B. Shankar; Brian F. Mcguinness; Douglas W. Hobbs; Yuefei Shao
Archive | 2006
Stuart B. Rosenblum; Seong Heon Kim; Qingbei Zeng; Michael K. C. Wong; Gopinadhan N. Anilkumar; Yueheng Jiang; Wensheng Yu; Joseph A. Kozlowski; Neng-Yang Shih; Bandarpalle B. Shankar; Brian F. Mcguinness; Guizhen Dong; Lisa Guise Zawacki; Douglas W. Hobbs; John J. Baldwin; Yuefei Shao
Archive | 2008
Frank Bennett; Qingbei Zeng; Srikanth Venkatraman; Mousumi Sannigrahi; Kevin X. Chen; Gopinadhan N. Anilkumar; Stuart B. Rosenblum; Joseph A. Kozlowski; F. George Njoroge
Archive | 2008
Gopinadhan N. Anilkumar; Stuart B. Rosenblum; Srikanth Venkatraman; F. George Njoroge; Joseph A. Kozlowski