244240-24-2

Basic information

• Product Name: LFM-A13
• Synonyms: α-cyano-β-hydroxy-β-methyl-n-(2,5-dibromophenyl)propenamide;(Z)-2-cyano-N-(2,5-dibroMophenyl)-3-hydroxybut-2-enaMide(LFM-A13);(Z)-2-cyano-N-(2,5-dibromophenyl)-3-hydroxybut-2-enamide;(2Z)-2-Cyano-N-(2,5-dibromophenyl)-3-hydroxy-2-butenamide;a-Cyano-b-hydroxy-b-methyl-N-(2,5-dibromophenyl)propenamide;2-cyano-N-(2,5-dibromophenyl) -3-oxobutanamide
• CAS NO: 244240-24-2
• Molecular Formula: C₁₁H₈Br₂N₂O₂
• Molecular Weight: 360.00142
• Product Categories: Inhibitors
• Mol File: 244240-24-2.mol

Chemical Properties

• Appearance: white/powder
• Storage Temp.: −20°C
• Solubility: DMSO: 15 mg/mL
• Stability: Stable for 2 years from date of purchase as supplied. PROTECT FROM MOISTURE. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: LFM-A13(CAS DataBase Reference)
• NIST Chemistry Reference: LFM-A13(244240-24-2)
• EPA Substance Registry System: LFM-A13(244240-24-2)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22
• Safety Statements: 36/37
• WGK Germany: 3
• Hazardous Substances Data: 244240-24-2(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
LFM-A13 is used as an inhibitor for targeted cancer therapy, specifically for anti-breast cancer activity. Its potent inhibition of Polo-like kinase (PLK) makes it a promising candidate for the development of new treatments against breast cancer.
Used in Immunology Research:
As a specific Bruton's tyrosine kinase (BTK) inhibitor, LFM-A13 is used in the study of BTK's role in various immune system functions and related diseases. This application aids in understanding the underlying mechanisms of immune responses and the potential for developing novel therapeutic strategies for immune disorders.
Used in Drug Development:
LFM-A13's selectivity for BTK and PLK makes it a valuable tool in the development of new drugs targeting these kinases. Its use in drug development can lead to the creation of more effective and targeted treatments for various diseases, including cancer and immune system-related conditions.

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].

IC 50

17.2 μm

References

1) Vassilev et al. (1999), Bruton’s tyrosine kinase as an inhibitor of the Fas/CD95 death-inducing signaling complex; J. Biol. Chem., 274 1646 2) Mahajan et al. (1999), Rational design and synthesis of a novel-anti-leukemic agent targeting Bruton’s tyrosine kinase (BTK), LFM-A13 [α-cyano-β-hydroxy-β-methyl-N-(2,5-dibromophenyl)propenamide]; J. Biol. Chem. 274 9587 3) Uckun et al. (2007) Anti-breast cancer activity of LFM-A13, a potent inhibitor of polo-like kinase (PLK); Bioorg. Med. Chem. 15 800

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Relevant articles and documents

α-Cyano-N-(2,5-dibromophenyl)-β-hydroxybut-2-enamide

The title compound, C11H8Br2N2O2 (LFM-A13), is the first reported BTK-specific tyrosine kinase inhibitor and the first antileukemic agent targeting BTK (Bruton's tyrosine kinase). The crystal structur

Large-scale synthesis of GMP grade α-cyano-β-hydroxy-β- methyl-N-(2,5-dibromophenyl) propenamide (LFM-A13), a new anti-cancer drug candidate

The leflunomide (CAS 75706-12-6) metabolite (LFM) analog α-cyano-β-hydroxy-β-methyl-N-(2,5-dibromophenyl)-propenamide (LFM-A13, DDE-28, CAS 244240-24-2), is a rationally designed inhibitor of the anti-apoptotic enzyme Bruton's tyrosine kinase (BTK). LFM-A

Structural influence on the intermolecular/intramolecular hydrogen bonding in solid state of substituted leflunomides: Evidence by X-ray crystal structure

We report the results of an X-ray crystal structure study of nine substituted leflunomide metabolite analogs (LFM). Comparison of the hydrogen bonding characteristics exhibited by these structurally distinct LFM analogs was especially informative about the inter- and intra-molecular hydrogen bonding patterns that exist in the crystal structure of individual compounds. All compounds had the strong intramolecular hydrogen bonds. In addition, with the exception of the 2,5-difluorophenyl substituted LFM analog, all other compounds formed inter- or intra-molecular hydrogen bonds with the halogen atom and the NH group. However, we found that the presence of a fluorine atom at the 2-position on the phenyl ring of the 2,5-difluoro and 2-fluoro derivatives resulted in only one intramolecular hydrogen bond in the structural framework. Conversely, the 3,5-difluoro substituted LFM analog had an intramolecular hydrogen bond common to the other halide substituted derivatives. The anomaly exhibited by the 2,5-difluoro and the 2-fluoro substituted compounds may be owing to the smaller size of fluorine atom in comparison with the chlorine and bromine atoms in the structures of the other analogs. The presence of a fluorine at the 2-position of the phenyl ring may disrupt the intermolecular hydrogen bonding that was observed for the other derivatives due to differences in the crystal packing for these molecules.

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

The specific inhibitor of the protein tyrosine kinase, Bruton's tyrosine kinase (BTK), α-cyano-β-hydroxy-β-methyl-N-(2,5-dibromophenyl)- propenamide (LFM-A13, CAS 244240-24-2), is a chemosensitizing antileukemic agent with antithrombotic properties. Oral