In vivo toxicity and antithrombotic profile of the oral formulation of the antileukemic agent, LFM-A13-F.

Abstract

The specific inhibitor of the protein tyrosine kinase, Bruton's tyrosine kinase (BTK), alpha-cyano-beta-hydroxy-beta-methyl-N-(2,5-dibromophenyl)-propenamide (LFM-A13, CAS 244240-24-2), is a chemosensitizing antileukemic agent with antithrombotic properties. Oral formulation of LFM-A13 (LFM-A13-F) did not cause acute, subacute or chronic toxicity in mice at dose levels up to 200 mg/kg. The in vivo antithrombotic activity of LFM-A13 was studied in a mouse model of collagen-induced fatal thromboembolism. Oral doses of LFM-A13-F dose dependently prevented collagen-induced thromboembolism in mice without causing bleeding. LFM-A13 could be combined with dipyridamole (CAS 58-32-2) without side effects. These results indicate that LFM-A13 may be particularly useful in the treatment of leukemia patients who are at risk for thromboembolic complications.

• Authors: Heather E Tibbles, Peter Samuel, Doug Erbeck, Sandeep Mahajan, Fatih M Uckun
• Journal: Arzneimittel-Forschung (Arzneimittelforschung) Vol. 54 Issue 6 Pg. 330-9 ( 2004) ISSN: 0004-4172 [Print] Germany
• PMID: 15281619 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Amides
• Fibrinolytic Agents
• LFM A13
• Nitriles
• Platelet Aggregation Inhibitors
• Dipyridamole
• Collagen

Topics

• Administration, Oral
• Amides (pharmacology, toxicity)
• Animals
• Bleeding Time
• Blood Cell Count
• Blood Coagulation (drug effects)
• Collagen
• Dipyridamole (pharmacology)
• Female
• Fibrinolytic Agents
• Mice
• Mice, Inbred BALB C
• Nitriles (pharmacology, toxicity)
• Platelet Aggregation Inhibitors (pharmacology)
• Thromboembolism (chemically induced)