Background:

Description:

IC50: 17.2 μM

Bruton’s tyrosine kinase (BTK), a member of the BTK/Tec family of protein tyrosine kinases, is a cytoplasmic PTK involved in signal transduction pathways regulating growth and differentiation of B-lineage lymphoid cells. BTK participates in signal transduction pathways initiated by the binding of a variety of extracellular ligands to their cell-surface receptors. LFM-A13 is a BTK-specific tyrosine kinase inhibitor.

In vitro: LFM-A13 inhibited recombinant BTK expressed in a baculovirus expression vector system. Besides its remarkable potency in BTK kinase assays, LFM-A13 was also found to be a highly specific inhibitor of BTK. Even at very high concentrations, LFM-A13 did not affect the activity of other protein tyrosine kinases [1].

In vivo: LFM-A13 exhibited a favorable pharmacokinetic behavior which was not adversely affected by the standard chemotherapy drugs and significantly improved the chemotherapy response and survival outcome of BCL-1 leukemia cells challenged mice. While only 14% of mice treated with the standard triple-drug combination treatment became long-term survivors, 41% of mice treated with this combination plus LFM-A13 survived long-term [2].

Clinical trial: Up to now, LFM-A13 is still in the preclinical development stage.

Reference:
[1] Mahajan S, Ghosh S, Sudbeck EA, Zheng Y, Downs S, Hupke M, Uckun FM.  Rational design and synthesis of a novel anti-leukemic agent targeting Bruton's tyrosine kinase (BTK), LFM-A13 [alpha-cyano-beta-hydroxy-beta-methyl-N-(2, 5-dibromophenyl)propenamide]. J Biol Chem. 1999 Apr 2;274(14):9587-99.
[2] Uckun FM, Zheng Y, Cetkovic-Cvrlje M, Vassilev A, Lisowski E, Waurzyniak B, Chen H, Carpenter R, Chen CL.  In vivo pharmacokinetic features, toxicity profile, and chemosensitizing activity of alpha-cyano-beta-hydroxy-beta- methyl-N-(2,5-dibromophenyl)propenamide (LFM-A13), a novel antileukemic agent targeting Bruton's tyrosine kinase. Clin Cancer Res. 2002 May;8(5):1224-33.
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