Pyrrolo[2,3-d]pyrimidines containing an extended 5-substituent as potent and selective inhibitors of lck I.

doi:10.1016/S0960-894X(00)00441-8

Paper

Pyrrolo[2,3-d]pyrimidines containing an extended 5-substituent as potent and selective inhibitors of lck I.

Published Oct 2, 2000 · Lee D. Arnold, D. J. Calderwood, Richard W. Dixon

Bioorganic & medicinal chemistry letters

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90

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1

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Abstract

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Study Snapshot

Pyrrolo[2,3-d]pyrimidines with a 5-(4-phenoxyphenyl) substituted are potent and selective inhibitors of LCK and IL2 production in cells.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Pyrrolo[2,3-d]pyrimidines containing an extended 5-substituent as potent and selective inhibitors of lck I.

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References

Structural analysis of the lymphocyte-specific kinase Lck in complex with non-selective and Src family selective kinase inhibitors.

The crystal structures of Lck kinase domains reveal that kinase selectivity can be achieved using small-molecule inhibitors that exploit subtle topological differences among protein kinases.

Crystal structure of Hck in complex with a Src family-selective tyrosine kinase inhibitor.

The crystal structure of Hck in complex with PP1 suggests a potential route for developing inhibitors specific for inactive Src family kinases.

T cell antigen receptor signal transduction.

Recent advances in TCR signal transduction include understanding the structure and function of ZAP-70, elucidating downstream substrates and pathways, and identifying molecules that negatively regulate TCR signaling.

Crystal structure of the Src family tyrosine kinase Hck

The crystal structure of Hck reveals that inhibition of enzymatic activity occurs through intramolecular interactions of SH2 and SH3, with catalytic domain elements displacement.

Three-dimensional structure of the tyrosine kinase c-Src

The structure of c-Src reveals how cellular signals or transforming mutations can break these interactions, resulting in an open, active kinase.

Citations

The preclinical discovery and development of zanubrutinib for the treatment of chronic lymphocytic leukemia.

Zanubrutinib is a 2nd generation covalent BTK inhibitor with superior efficacy and tolerability, making it a preferred treatment choice for chronic lymphocytic leukemia.

Membrane-bound Merkel cell polyomavirus middle T protein constitutively activates PLCγ1 signaling through Src-family kinases

The Merkel cell polyomavirus middle T protein activates PLC1 signaling through Src-family kinases, leading to inflammatory cell signaling in Merkel cell carcinomas.

ATP-site inhibitors induce unique conformations of the acute myeloid leukemia-associated Src-family kinase, Fgr.

ATP-site inhibitors A-419259 and TL02-59 induce unique conformations of Fgr, which may help design anti-leukemic agents.

Zap70 Regulates TCR-Mediated Zip6 Activation at the Immunological Synapse

Zap70 plays a crucial role in regulating T-cell responses by regulating the interaction between Zip6-mediated zinc influx and TCR activation in human CD4+ T cells.

PD-1 suppresses TCR-CD8 cooperativity during T-cell antigen recognition

PD-1 inhibits T-cell activation by disrupting the cooperative TCR-pMHC-CD8 trimolecular interaction, explaining its potent inhibitory function and value as a target for clinical intervention.