Home
Resources
Publications
Preclinical Toxicity and Pharmacokinetics of the Bruton's Tyrosine Kinase-Targeting Anti-Leukemic Drug Candidate, alpha-cyano-beta-hydroxy-beta-methyl-N- (2,5-dibromophenyl) Propenamide (LFM-A13)

Preclinical Toxicity and Pharmacokinetics of the Bruton's Tyrosine Kinase-Targeting Anti-Leukemic Drug Candidate, alpha-cyano-beta-hydroxy-beta-methyl-N- (2,5-dibromophenyl) Propenamide (LFM-A13)

Fatih M Uckun, Heather Tibbles, Taracad Venkatachalam, Darin DuMez, Douglas Erbeck

Arzneimittelforschung. 2007;57(1):31-46.

PMID: 17341007

Abstract:

The leflunomide (CAS 75706-12-6) metabolite (LFM) analog alpha-cyano-beta-hydroxy-beta-methyl-N-(2,5-dibromophenyl)-propenamide (LFM-A13, DDE-28, CAS 244240-24-2) is a rationally-designed specific inhibitor of the TEC family protein tyrosine kinase, Bruton's tyrosine kinase (BTK). LFM-A13 exhibited favorable pharmacokinetics in CD-1 mice, BALB/c mice, rats, and dogs. The intraperitoneal bioavailability was estimated to be -100%, while the oral bioavailability was -30%. LFM-A13 enters, but does not bind to multiple tissues followed by a rapid elimination from most of the tissues. Limited distribution of LFM-A13 to extravascular tissues and its corresponding low volume of distribution could be attributed to its plasma protein binding. LFM-A13 was not toxic to mice, rats, or dogs at daily dose levels as high as 100 mg/kg. LFM-A13 formulated as a suspension and hard gelatin capsules for oral administration showed a rapid absorption and favorable pharmacokinetic features. These preclinical research studies provide the basis for future pre-IND studies and clinicaldevelopment of LFM-A13 as an intravenously or orally administered new anti-leukemia agent targeting BTK.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP62004357	LFM-A13 - CAS 62004-35-7		62004-35-7	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: