LFM-A13   Click here for help

GtoPdb Ligand ID: 9262

Synonyms: α-cyano-beta-hydroxy-β-methyl-N-(2, 5-dibromophenyl)propenamide | alpha-cyano-beta-hydroxy-beta-methyl-N-(2, 5-dibromophenyl)propenamide
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: LFM-A13 is a potent, cell-permeable, reversible, substrate competitive, and specific inhibitor of Bruton's tyrosine kinase (BTK) [1]. It was the first reported BTK-selective tyrosine kinase inhibitor and the first anti-leukemic agent targeting BTK. Investigated preclinically for B-cell non-Hodgkin's lymphoma [5-6].
Structurally LFM-A13 is an analogue of a metabolite of the antirheumatic drug leflunomide. The Mahajan et al. article also reports a three-dimensional homology model suggesting an energetically favorable position of LFM-A13 docked within BTK's catalytic site [1].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

LFM-A13 is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 4
Hydrogen bond donors 2
Rotatable bonds 3
Topological polar surface area 73.12
Molecular weight 357.9
XLogP 3.13
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES CC(=C(C(=O)Nc1cc(Br)ccc1Br)C#N)O
Isomeric SMILES C/C(=C(/C(=O)Nc1cc(Br)ccc1Br)\C#N)/O
InChI InChI=1S/C11H8Br2N2O2/c1-6(16)8(5-14)11(17)15-10-4-7(12)2-3-9(10)13/h2-4,16H,1H3,(H,15,17)/b8-6-
InChI Key UVSVTDVJQAJIFG-VURMDHGXSA-N
References
1. Mahajan S, Ghosh S, Sudbeck EA, Zheng Y, Downs S, Hupke M, Uckun FM. (1999)
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, 274 (14): 9587-99. [PMID:10092645]
2. Uckun F, Dibirdik I, Sarkissian A, Qazi S. (2011)
In vitro and in vivo chemosensitizing activity of LFM-A13, a dual-function inhibitor of Bruton's tyrosine kinase and polo-like kinases, against human leukemic B-cell precursors.
Arzneimittelforschung, 61 (4): 252-9. [PMID:21650085]
3. Uckun FM. (2007)
Chemosensitizing anti-cancer activity of LFM-A13, a leflunomide metabolite analog targeting polo-like kinases.
Cell Cycle, 6 (24): 3021-6. [PMID:18073537]
4. Uckun FM, Dibirdik I, Qazi S, Vassilev A, Ma H, Mao C, Benyumov A, Emami KH. (2007)
Anti-breast cancer activity of LFM-A13, a potent inhibitor of Polo-like kinase (PLK).
Bioorg Med Chem, 15 (2): 800-14. [PMID:17098432]
5. Uckun FM, Tibbles H, Venkatachalam T, DuMez D, Erbeck D. (2007)
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).
Arzneimittelforschung, 57 (1): 31-46. [PMID:17341007]
6. Uckun FM, Zheng Y, Cetkovic-Cvrlje M, Vassilev A, Lisowski E, Waurzyniak B, Chen H, Carpenter R, Chen CL. (2002)
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, 8 (5): 1224-33. [PMID:12006542]