LFM-A13 is a potent and selective inhibitor of Bruton's tyrosine kinase (BTK). LFM-A13 inhibits recombinant BTK with an IC50 value of 2.5 μM and has no activity on other protein kinases ( including JAK1, JAK3, HCK, EGFR kinase and insulin receptor kinase) at concentrations of up to 278 μM. In BCL-1 cells, NALM-6 cells, or normal BALB/c splenocytes, LFM-13 inhibits the enzymatic activity of BTK in BCL-1 cells without affecting the BTK protein expression levels. In human neutrophils, LFM-A13 decreases the tyrosine phosphorylation induced by fMet-Leu-Phe and inhibits the production of superoxide anions and the stimulation of adhesion, chemotaxis, and phospholipase D activity. In vivo, LFM-A13 inhibits osteoclast activity in primary myeloma-bearing SCID-rab mice, prevents myeloma-induced bone resorption and suppresss myeloma growth.
|Animal models||BALB/c mice bearing BCL-1 leukemia|
|Formulation||Suspended in 10% DMSO in PBS|
|Dosages||50 mg/kg/day, twice daily|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
|Solubility||DMSO: ≥ 40 mg/mL warmed|
Role of Bruton's tyrosine kinase in myeloma cell migration and induction of bone disease.
Bam R, et al. Am J Hematol. 2013 Jun;88(6):463-71. PMID: 23456977.
Subtlety of the structure-affinity and structure-efficacy relationships around a nonpeptide oxytocin receptor agonist.
Frantz, et al. J Med Chem. 2010;53: 1546. PMID: 20104850.
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.
Uckun FM, et al. Clin Cancer Res. 2002 May;8(5):1224-33. PMID: 12006542.
|Related BTK Products|
Remibrutinib (LOU064) is a potent and highly selective covalent Inhibitor of Bruton's Tyrosine Kinase (BTK) with IC50 value of 1 nM.
Tolebrutinib, also known as SAR442168, is a Bruton tyrosine kinase (BTK) inhibitor, with IC50 values of 0.4 nM and 0.7 nM in Ramos B cells and HMC microglia cells, respectively.
Orelabrutinib is an orally active and irreversible inhibitor of Bruton's tyrosine kinase (BTK).
Zanubrutinib (BGB-3111) is a potent and highly selective small molecule inhibitor of Bruton's tyrosine kinase (BTK).
ARQ 531 is a potent reversible inhibitor of BTK (IC50 = 0.85 nM), exhibits potent antitumor activity in ibrutinib-resistant diffuse large B-cell lymphoma.
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