LFM-A13

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种高度特异性的 BTK 抑制剂，Ki 为 1.4 uM，IC50 为 17.2 uM。

A highly specific inhibitor of BTK with Ki of 1.4 uM, IC50 of 17.2 uM; shows no activity against EGFR, IRK, JAK1, JAK3, or HCK; enhances the sensitivity to ceramide- or vincristine-induced apoptosis in BTK+ B-lineage leukemic cells; prolongs the median survival time of VPL-treated mice; also inhibits Plk3 with IC50 of 61 uM, prevented bipolar mitotic spindle assembly in human breast cancer cells and glioblastoma cells, delays tumor progression in MMTV/neu transgenic mouse model of HER2 positive breast cancer.

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. 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. 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.

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.) attenuatesmammary tumorigenesis in mice. LFM-A13 alone or in combination with paclitaxel shows marked effect on the 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. 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.

LFM A13 | LFM-A13 | LFM A13

Tyrosine Kinase

BTK

BTK

Cancer

——

244240-24-2

360.0014

C11H8Br2N2O2

>98% (HPLC)

DMSO: ≥ 42 mg/mL

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

2-Butenamide, 2-cyano-N-(2,5-dibromophenyl)-3-hydroxy-,(2Z)-

(-20℃)

With Ice Pack

≥ 2 years