| 摘要 |
PROBLEM TO BE SOLVED: To provide therapeutic use of an intracellular kinase inhibitor in patients with T cell malignancies, B cell malignancies, autoimmune disorders and transplanted organs.SOLUTION: A protein kinase inhibitor represented by Formula (II) which binds to a DKC triad kinase active site, comprising: (a) a proton acceptor positioned within hydrogen-bonding distance to an amino group of a lysine of a catalytic dyad in the kinase active site; (b) an abstractable proton in hydrogen bonding proximity to an aspartate of the catalytic dyad in the kinase active site; (c) a leaving group where further electronic rearrangement leads to the &bgr;-elimination of the leaving group, whereby a Michael acceptor in the inhibitor is created; and (d) a kinase binding moiety with affinity for a portion of the ATP binding site selected from the group consisting of the hinge region of the kinase, several hydrophobic residues, hydrophilic residues, and a combination thereof.SELECTED DRAWING: None |
