A dual function anti-leukemic agent with anti-thrombotic activity.
Here we report that treatment with the anti-leukemic compound, LFM-A13 resulted in SYK kinase activation and caused distinct shape changes in platelets. Also provided is electron microscopic evidence that similar shape changes are observed in platelets from XID mice. We propose that LFM-A13 induces a conformational change in the PH domain of BTK and causes BTK to associate with PIP2 which effects actin bundling and shape change.
Tibbles
Heather
H
Parker Hughes Cancer Center, Parker Hughes Institute, St Paul, MN 55113, USA.
Vassilev
Alexei
A
Uckun
Fatih M
FM
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000577:Amides / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004792:Enzyme Precursors / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007938:Leukemia / Q000188:drug therapy*; D009570:Nitriles / Q000494:pharmacology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000072377:Syk Kinase
D000577:Amides; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D005343:Fibrinolytic Agents; D047908:Intracellular Signaling Peptides and Proteins; C118451:LFM A13; D009570:Nitriles; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C000625951:Btk protein, mouse; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse