Introduction of 244240-24-2 :
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; LFM-A13 shows no effects on JAK1 and JAK3, Src family kinase HCK, EGFR and IRK. IC50 & Target: IC50: 2.5 μM (BTK)[1], 10 μM (Plx1), 61 μM (PLK3)[4] In Vitro: LFM-A13 significantly inhibits BTK activity with an IC50 of 6.2 ± 0.3 μg/mL (= 17.2 ± 0.8 μM). The calculated Kis of LFM-A13 for BTK, JAK1, JAK3, IRK, EGFR and HCK are 1.4, 110, 148, 31.6, 166 and 214 μM. LFM-A13 (200 μM) markedly increases the chemosensitivity of ALL-1 cells to ceramide-induced apoptosis[1]. LFM-A13 (100 μM) suppresses Epo-induced phosphorylation of EpoR, Jak2, Btk, Stat5 and Erk1/2 in R10 cells. LFM-A13 (100 μM) inhibits auto-phosphorylation of Jak2, Tec and Btk rather than Lyn kinase auto-phosphorylation in COS cells[2]. LFM-A13 potently inhibits Plx1 with IC50 of 10 μM; also inhibits BRK, BMX, FYN and with IC50s of 267, 281, 240 and 215 μM[4]. In Vivo: LFM-A13 (25, 50 and 100 mg/kg) shows no apparent toxicity to rats. LFM-A13 (50 mg/kg, three times a week, i.p.) attenuates DMBA-induced mammary tumorigenesis in mice. LFM-A13 alone or in combination with paclitaxel shows marked effect on the DMBA-induced breast tumor incidence, mean tumor numbers, average tumor weight, and size in BALB/c mice. LFM-A13 (50 mg/kg, three times a week, i.p.) significantly decreases PLK1, cyclin D1, CDK-4, P53 and Bcl-2 expression, but increases the expression of p21, IκB, Bax and caspase 3 expression in mice[3]. LFM-A13 (200 mg/kg) does not cause hematologic toxicity in rats. 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[4].
