LYN - SPR Binding Assay

Our service for comprehensive kinetic characterization of your small molecule kinase inhibitors

Theoretical background: Lyn is a Src family kinase primary expressed in hematopoietic cells, predominantly in B cells. The modular structure is formed by an N-terminal tail, a Src homology 3 (SH3) domain, a SH2 domain, the catalytic core and a C-terminal negative regulatory domain. Lyn is associated with the BCR in resting cells and serves upon antigen binding and BCR aggregation to phosphorylate tyrosine containing ITAM motifs on Ig-α/β. Furthermore, Lyn activation results in CD22 phosphorylation and the recruitment and activation of the tyrosine phosphatase SHP-1, which downmodulates BCR-mediated signaling. Lyn is an important candidate target for specific therapy of prostate cancer, colon cancer and acute myeloid leukemia.

 

Lyn and inhibitors: The pyrazolo-pyrimidines PP1 and the related compound PP2 are widely used ATP competitive Src family kinase inhibitors showing a good potency against various kinases as Src, Lck, Lyn (PP2 IC50 = 9 nM [1]) and Fyn. SU6656 is a cell permeable and potent inhibitor of Lyn (IC50 = 35 nM [1]), Fyn, Yes and Src but a rather poor inhibitor of Lck. Dasatinib, initially isolated as a dual Src/Abl inhibitor has a high affinity against Abl, Yes, Lyn (KD = 0.57 nM [2]) and Lck too and is used in several clinical trials.

 

 

Figure: Real-time kinetic analysis of kinase inhibitor Dasatinib binding to LYN using surface plasmon resonance.


[1] Williams NK et al. (2009) J Biol Chem. 2009 Jan 2;284(1):284-91.

[2] Karaman MW et al. (2008) Nat Biotechnol. 2008 Jan;26(1):127-32.

 

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