信号传导抑制剂治疗骨髓增生异常综合征。

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Bachegowda L, Gligich O, Mantzaris我Schinke C, Wyville D, Carrillo T,布伦瑞克我,Steidl U,胆量

信号传导抑制剂治疗骨髓增生异常综合征。

J内科杂志杂志。2013年7月10,骑车。doi: 10.1186 / 1756-8722-6-50。

PubMed ID

23841999 (在PubMed

]

文摘

骨髓增生异常综合征(MDS)是一组血液疾病的特点是无效造血作用,减少血液中计数结果。虽然MDS转化为白血病,大部分的发病率,这些患者是由于长期的低血液计数。传统的细胞毒性药物用于治疗MDS取得了一些令人鼓舞的结果,但有许多不利影响主要是老年患者人群。有针对性的干预措施,旨在扭转骨髓衰竭,增加外周血计数将在这群患者是有利的。研究已经证明over-activated信号myelo-suppressive及等细胞因子tnf和干扰素在MDS造血干细胞。针对这些信号级联可能会在MDS的治疗。p38激酶途径地图,在MDS持续激活,是细胞因子刺激激酶,促进异常的一个例子在MDS干细胞和祖细胞的凋亡。进行469 - 614和新办- p38 MAPK抑制剂已用于临床试验,显示活动MDS患者的一个子集。及信号已经被小分子抑制剂的治疗目标及受体激酶,ly - 2157299,鼓励临床结果。除了受体激酶抑制,及超级的家人和BMP配体也被配体陷阱的目标化合物像Sotatercept (ace - 011)和ace - 536。 The multikinase inhibitor, ON-01910.Na (Rigosertib) has demonstrated early signs of efficacy in reducing the percentage of leukemic blasts and is in advanced stages of clinical testing. Temsirolimus, Deforolimus and other mTOR inhibitors are being tested in clinical trials and have shown preclinical efficacy in CMML. EGF receptor inhibitors, Erlotinib and Gefitinib have shown efficacy in small trials that may be related to off target effects. Cell cycle regulator inhibitors such as Farnesyl transferase inhibitors (Tipifarnib, Lonafarnib) and MEK inhibitor (GSK1120212) have shown acceptable toxicity profiles in small studies and efforts are underway to select mutational subgroups of MDS and AML that may benefit from these inhibitors. Altogether, these studies show that targeting various signal transduction pathways that regulate hematopoiesis offers promising therapeutic potential in this disease. Future studies in combination with high resolution correlative studies will clarify the subgroup specific efficacies of these agents.

DrugBank数据引用了这篇文章

药物靶点

药物	目标	类	生物	药理作用	行动
Ridaforolimus	丝氨酸/ threonine-protein激酶mTOR	蛋白质	人类	是的	抑制剂	细节