LFM-A13

LFM-A13 is a potent BTK, JAK2, PLK inhibitor, inhibits recombinant BTK, Plx1 and PLK3 with IC₅₀ s of 2.5 μM, 10 μM and 61 μM. LFM-A13 has antiproliferative activity and anticancer activity. LFM-A13 can be used in cancer-related research ^{[1] [3] [4]}

In Vivo, LFM-A13 (10 or 50 mg/kg; i.p.) exhibits anti-tumor effects dose dependently in the MMTV/Neu transgenic mouse model of breast cancer^[3]. FM-A13 (50 mg/kg; tiw; i.p.) attenuates DMBA-induced mammary tumorigenesis in mice by modulating a variety of factors associated with cell cycle, survival and apoptosis^[4].

In Vitro, LFM-A13 (100 μM; 4 h) inhibits Epo-induced phosphorylation of EpoR, JAK2, BTK, STAT5, and ERK1/2 in R10 cells^[2]. LFM-A13 (100 μM; transfection 48 h) inhibits the autophosphorylation of JAK2, Tec and BTK in COS cells without affecting the autophosphorylation of Lyn kinase^[2]. LFM-A13 potently inhibits Plx1 with IC₅₀ of 10 μM; also inhibits BRK, BMX, FYN and Met with IC50s of 267, 281, 240 and 215 μM, respectively^[3].

References:
[1]. Mahajan S, et al. 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.
[2]. van den Akker E, et al. The Btk inhibitor LFM-A13 is a potent inhibitor of Jak2 kinase activity. Biol Chem. 2004 May;385(5):409-13.
[3]. Uckun FM, et al. 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.
[4]. Sahin K, et al. 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.