LFM-A13性质、用途与生产工艺
LFM-A13是一种特异性布鲁顿氏酪氨酸激酶(BTK),IC50为2.5 μM,选择性比其他蛋白激酶,包括JAK1,JAK2,HCK,EGFR,和 IRK高100多倍。
In BTK+ B-lineage leukemic cells, LFM-A13 enhances their sensitivity to ceramide- or vincristine-induced apoptosis. In BCL-1 cells, NALM-6 cells, or normal BALB/c splenocytes, LFM-13 inhibits the enzymatic activity of BTK in BCL-1 cells without affecting the BTK protein expression levels In human neutrophils, LFM-A13 decreases the tyrosine phosphorylation induced by fMet-Leu-Phe and inhibits the production of superoxide anions and the stimulation of adhesion, chemotaxis, and phospholipase D activity.
In BALB/c mice bearing BCL-1 leukemia, combination of LFM-A13 (50 mg/kg/day i.p.) and the standard triple-drug VPL prolongs the median survival time. In primary myeloma-bearing SCID-rab mice, LFM-A13 inhibits osteoclast activity, prevents myeloma-induced bone resorption and suppresss myeloma growth.
LFM-A13是一种特异性布鲁顿氏酪氨酸激酶(BTK)抑制剂,IC50为2.5 μM,选择性比其他蛋白激酶,包括JAK1,JAK2,HCK,EGFR,和 IRK高100多倍。
Target | Value |
BTK
(cell-free assay)
|
1.4 μM(Ki)
|
在BTK+ B系白血病细胞中,LFM-A13增强它们对神经酰胺或长春新碱诱导的细胞凋亡的敏感性。在BCL-1细胞,NALM-6细胞,或正常BALB/c脾细胞,LFM-13抑制BCL-1细胞中BTK的酶活性,而不影响BTK蛋白表达水平。在人嗜中性粒细胞中,LFM-A13降低fMet-Leu-Phe诱导的酪氨酸磷酸化,并抑制超氧阴离子的产生和粘附,趋化的刺激,以及磷脂酶D活性。
在负荷BCL-1白血病的BALB/c小鼠体内,LFM-A13 (50 mg/kg/day i.p.)与标准三联药物VPL结合延长平均存活时间。在负荷原代骨髓瘤的SCID-rab小鼠体内,LFM-A13抑制破骨细胞活性,防止骨髓瘤诱导的骨吸收,并抑制骨髓瘤的生长。
LFM-A13
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