LFM-A13
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MedKoo CAT#: 401531

CAS#: 244240-24-2

Description: LFM-A13 is a potent and selective inhibitor of Bruton's tyrosine kinase (BTK). LFM-A13 may be useful as a new class of chemosensitizing and apoptosis-promoting antileukemic agents for treatment of patients with chemotherapy-resistant B-lineage leukemias or lymphomas.

Chemical Structure

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LFM-A13
CAS# 244240-24-2
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 401531
Name: LFM-A13
CAS#: 244240-24-2
Chemical Formula: C11H8Br2N2O2
Exact Mass: 357.90
Molecular Weight: 360.005
Elemental Analysis: C, 36.70; H, 2.24; Br, 44.39; N, 7.78; O, 8.89

Price and Availability

Size Price Availability Quantity
50mg USD 250 2 Weeks
100mg USD 400 2 Weeks
200mg USD 650 2 Weeks
500mg USD 950 2 Weeks
1g USD 1450
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Synonym: LFM A13; LFM-A13; LFM A13

IUPAC/Chemical Name: 2-Cyano-N-(2,5-dibromophenyl)-3-hydroxy-2-butenamide

InChi Key: UVSVTDVJQAJIFG-VURMDHGXSA-N

InChi Code: 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-

SMILES Code: C/C(O)=C(C#N)/C(NC1=CC(Br)=CC=C1Br)=O

Appearance: Solid powder

Purity: >98%

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >5 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

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Product Data:
Product Data
Instruction:
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Biological target: LFM-A13 is a potent BTK, JAK2, PLK inhibitor, inhibits recombinant BTK, Plx1 and PLK3 with IC50s of 2.5 μM, 10 μM and 61 μM.
In vitro activity: Human osteoclast precursors also expressed BTK and cell-surface CXCR4 and migrated toward SDF-1. LFM-A13 suppressed migration and differentiation of osteoclast precursors as well as bone-resorbing activity of mature osteoclasts. Reference: Am J Hematol. 2013 Jun;88(6):463-71. https://pubmed.ncbi.nlm.nih.gov/23456977/
In vivo activity: At the molecular level, the administration of LFM-A13 hindered mammary gland carcinoma development by regulating the expression of PLK1, cell cycle-regulating proteins cyclin D1, cyclin dependent kinase-4 (CDK-4), and the CDK inhibitor, p21. Moreover, LFM-A13 treatment upregulated the levels of IκB, the pro-apoptotic proteins Bax, and caspase-3, and down-regulated p53 and the antiapoptotic protein Bcl-2 in mammary tumors. Reference: Invest New Drugs. 2018 Jun;36(3):388-395. https://pubmed.ncbi.nlm.nih.gov/29139009/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 20.0 55.55
DMF:PBS (pH 7.2) (1:2) 0.3 0.83
DMSO 26.0 72.22

Preparing Stock Solutions

The following data is based on the product molecular weight 360.01 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Bam R, Ling W, Khan S, Pennisi A, Venkateshaiah SU, Li X, van Rhee F, Usmani S, Barlogie B, Shaughnessy J, Epstein J, Yaccoby S. Role of Bruton's tyrosine kinase in myeloma cell migration and induction of bone disease. Am J Hematol. 2013 Jun;88(6):463-71. doi: 10.1002/ajh.23433. Epub 2013 Mar 28. PMID: 23456977; PMCID: PMC3971999. 2. van den Akker E, van Dijk TB, Schmidt U, Felida L, Beug H, Löwenberg B, von Lindern M. The Btk inhibitor LFM-A13 is a potent inhibitor of Jak2 kinase activity. Biol Chem. 2004 May;385(5):409-13. doi: 10.1515/BC.2004.045. PMID: 15196000. 3. Sahin K, Tuzcu M, Yabas M, Orhan C, Sahin N, Ozercan IH. LFM-A13, a potent inhibitor of polo-like kinase, inhibits breast carcinogenesis by suppressing proliferation activity and inducing apoptosis in breast tumors of mice. Invest New Drugs. 2018 Jun;36(3):388-395. doi: 10.1007/s10637-017-0540-2. Epub 2017 Nov 15. PMID: 29139009. 4. Uckun FM, Dibirdik I, Qazi S, Vassilev A, Ma H, Mao C, Benyumov A, Emami KH. Anti-breast cancer activity of LFM-A13, a potent inhibitor of Polo-like kinase (PLK). Bioorg Med Chem. 2007 Jan 15;15(2):800-14. doi: 10.1016/j.bmc.2006.10.050. Epub 2006 Oct 26. PMID: 17098432.
In vitro protocol: 1. Bam R, Ling W, Khan S, Pennisi A, Venkateshaiah SU, Li X, van Rhee F, Usmani S, Barlogie B, Shaughnessy J, Epstein J, Yaccoby S. Role of Bruton's tyrosine kinase in myeloma cell migration and induction of bone disease. Am J Hematol. 2013 Jun;88(6):463-71. doi: 10.1002/ajh.23433. Epub 2013 Mar 28. PMID: 23456977; PMCID: PMC3971999. 2. van den Akker E, van Dijk TB, Schmidt U, Felida L, Beug H, Löwenberg B, von Lindern M. The Btk inhibitor LFM-A13 is a potent inhibitor of Jak2 kinase activity. Biol Chem. 2004 May;385(5):409-13. doi: 10.1515/BC.2004.045. PMID: 15196000.
In vivo protocol: 1. Sahin K, Tuzcu M, Yabas M, Orhan C, Sahin N, Ozercan IH. LFM-A13, a potent inhibitor of polo-like kinase, inhibits breast carcinogenesis by suppressing proliferation activity and inducing apoptosis in breast tumors of mice. Invest New Drugs. 2018 Jun;36(3):388-395. doi: 10.1007/s10637-017-0540-2. Epub 2017 Nov 15. PMID: 29139009. 2. Uckun FM, Dibirdik I, Qazi S, Vassilev A, Ma H, Mao C, Benyumov A, Emami KH. Anti-breast cancer activity of LFM-A13, a potent inhibitor of Polo-like kinase (PLK). Bioorg Med Chem. 2007 Jan 15;15(2):800-14. doi: 10.1016/j.bmc.2006.10.050. Epub 2006 Oct 26. PMID: 17098432.

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1: Uckun F, Dibirdik I, Sarkissian A, Qazi S. 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. 2011;61(4):252-9. doi: 10.1055/s-0031-1296196. PubMed PMID: 21650085.

2: Uckun FM. Chemosensitizing anti-cancer activity of LFM-A13, a leflunomide metabolite analog targeting polo-like kinases. Cell Cycle. 2007 Dec 15;6(24):3021-6. Epub 2007 Sep 26. PubMed PMID: 18073537.

3: DuMez D, Venkatachalam TK, Uckun FM. Large-scale synthesis of GMP grade alpha-cyano-beta-hydroxy-beta-methyl-N-(2,5-dibromophenyl) propenamide (LFM-A13), a new anti-cancer drug candidate. Arzneimittelforschung. 2007;57(3):155-63. PubMed PMID: 17469650.

4: Uckun FM, Tibbles H, Venkatachalam T, DuMez D, Erbeck D. 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. 2007;57(1):31-46. PubMed PMID: 17341007.

5: Uckun FM, Dibirdik I, Qazi S, Vassilev A, Ma H, Mao C, Benyumov A, Emami KH. Anti-breast cancer activity of LFM-A13, a potent inhibitor of Polo-like kinase (PLK). Bioorg Med Chem. 2007 Jan 15;15(2):800-14. Epub 2006 Oct 26. PubMed PMID: 17098432.

6: Tibbles HE, Samuel P, Erbeck D, Mahajan S, Uckun FM. In vivo toxicity and antithrombotic profile of the oral formulation of the antileukemic agent, LFM-A13-F. Arzneimittelforschung. 2004;54(6):330-9. PubMed PMID: 15281619.

7: van den Akker E, van Dijk TB, Schmidt U, Felida L, Beug H, Löwenberg B, von Lindern M. The Btk inhibitor LFM-A13 is a potent inhibitor of Jak2 kinase activity. Biol Chem. 2004 May;385(5):409-13. PubMed PMID: 15196000.

8: Uckun FM, Vassilev A, Bartell S, Zheng Y, Mahajan S, Tibbles HE. The anti-leukemic Bruton's tyrosine kinase inhibitor alpha-cyano-beta-hydroxy-beta-methyl-N-(2,5-dibromophenyl) propenamide (LFM-A13) prevents fatal thromboembolism. Leuk Lymphoma. 2003 Sep;44(9):1569-77. PubMed PMID: 14565661.

9: Gilbert C, Levasseur S, Desaulniers P, Dusseault AA, Thibault N, Bourgoin SG, Naccache PH. Chemotactic factor-induced recruitment and activation of Tec family kinases in human neutrophils. II. Effects of LFM-A13, a specific Btk inhibitor. J Immunol. 2003 May 15;170(10):5235-43. PubMed PMID: 12734372.

10: Uckun FM, Zheng Y, Cetkovic-Cvrlje M, Vassilev A, Lisowski E, Waurzyniak B, Chen H, Carpenter R, Chen CL. 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. 2002 May;8(5):1224-33. PubMed PMID: 12006542.

11: Mahajan S, Ghosh S, Sudbeck EA, Zheng Y, Downs S, Hupke M, Uckun FM. 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. 1999 Apr 2;274(14):9587-99. PubMed PMID: 10092645.