SF-2558HA(SF-2558HA) - 药物靶点：HDACs x PI3Kα_在研适应症：肿瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名

PI3K/HDAC inhibitor (SignalRx)、SRX-3636、SF-2558HA

靶点

HDACs x PI3Kα

作用机制

HDAC抑制剂(组蛋白去乙酰化酶家族抑制剂)、PI3Kα抑制剂(磷脂酰肌醇3-激酶α抑制剂)

治疗领域

肿瘤

在研适应症

肿瘤

非在研适应症-

原研机构

SignalRx Pharmaceuticals, Inc.

在研机构

SignalRx Pharmaceuticals, Inc.

非在研机构-

最高研发阶段药物发现

首次获批日期-

最高研发阶段(中国)-

特殊审评-

关联

100 项与 SF-2558HA 相关的临床结果

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100 项与 SF-2558HA 相关的转化医学

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100 项与 SF-2558HA 相关的专利（医药）

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326

项与 SF-2558HA 相关的文献（医药）

2024-12-31·JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY

Design and synthesis of triazolopyridine derivatives as potent JAK/HDAC dual inhibitors with broad-spectrum antiproliferative activity

Article

作者: Xu, Zhengshui ; Chen, Xin ; Ye, Changchun ; Liu, Shiyuan ; Wang, Xingjie ; Chen, Zilu ; Kong, Ranran ; Shi, Jing

A series of triazolopyridine-based dual JAK/HDAC inhibitors were rationally designed and synthesised by merging different pharmacophores into one molecule. All triazolopyridine derivatives exhibited potent inhibitory activities against both targets and the best compound 4-(((5-(benzo[d][1, 3]dioxol-5-yl)-[1, 2, 4]triazolo[1, 5-a]pyridin-2-yl)amino)methyl)-N-hydroxybenzamide (19) was dug out. 19 was proved to be a pan-HDAC and JAK1/2 dual inhibitor and displayed high cytotoxicity against two cancer cell lines MDA-MB-231 and RPMI-8226 with IC₅₀ values in submicromolar range. Docking simulation revealed that 19 fitted well into the active sites of HDAC and JAK proteins. Moreover, 19 exhibited better metabolic stability in vitro than SAHA. Our study demonstrated that compound 19 was a promising candidate for further preclinical studies.

2024-12-01·Molecular biology reports

PXMP4 promotes gastric cancer cell epithelial-mesenchymal transition via the PI3K/AKT signaling pathway

Article

作者: Wang, Beixi ; Mi, Yongrun ; Zhang, Jingyu ; Li, Ruiyuan ; Li, Na ; Wan, Zhidan ; He, Guoyang ; Dong, Xiangyang ; Wang, Wenxin ; Li, Wei ; Xu, Zishan

BACKGROUND:

Peroxisomal membrane protein 4 (PXMP4), a member of the peroxisome membrane protein PXMP2/4 family, participates in the progression of several malignant cancers. Nevertheless, the effect of PXMP4 in the development of gastric cancer (GC) is still unknown. As a result, the focus of this investigation was to elucidate the potential mechanisms of PXMP4 in GC.

METHODS AND RESULTS:

Firstly, bioinformatics analysis results showed higher expression of PXMP4 in GC tissues. Secondly, clinical analysis of 57 patients with GC revealed correlations between PXMP4 expression and differentiation, depth of invasion, as well as TNM stage. Furthermore, individuals with elevated PXMP4 expression in GC exhibited an unfavorable prognosis. In vitro data showed the involvement of knockdown/overexpression of PXMP4 in the proliferation, invasion, and migration of GC cells, and triggering the epithelial-mesenchymal transition (EMT) of GC cells through the activation of the PI3K/AKT signaling pathway. LY294002, a PI3K/AKT inhibitor, inhibited the expression of PI3K/AKT-related proteins but did not affect the expression of PXMP4.

CONCLUSIONS:

These findings indicate that PXMP4 potentially functions as an upstream molecule in the PI3K/AKT pathway, governing the EMT process in GC.

2024-11-01·EUROPEAN JOURNAL OF PHARMACOLOGY

The efficacy and safety of PI3K and AKT inhibitors for patients with cancer: A systematic review and network meta-analysis

Review

作者: Xun, Fanghua ; Hui, Fuhai ; Song, Aigang ; Wang, Chengkang ; Xu, Ziang ; Ren, Tianshu ; Wang, Shuai ; Xu, Chang ; Hou, Shanbo ; Zhang, Yingshi ; Zhao, Qingchun ; Zheng, Fangyuan ; Xu, Xiangbo ; Geng, Hefeng ; Zhang, Tianqi ; Yang, Kaisi

BACKGROUND:

Inhibiting PI3K/AKT pathway activation may hinder the occurrence and progression of cancer. The aim of this study was to evaluate the efficacy and safety of the PI3K/AKT inhibitors and determine the most appropriate inhibitor for different cancer types.

METHODS:

Electronic databases up to June 2024 were used to examine the efficacy and safety of PI3K inhibitors (alpelisib, copanlisib, duvelisib, and idelalisib) and AKT inhibitors (capivasertib, ipatasertib and MK-2206) for the treatment of cancer. Data was assessed with a random-effect pairwise and network meta-analysis. Randomized controlled trials and retrospective studies were eligible if they compared PI3K or AKT inhibitors with non-PI3K/AKT controls with no restriction.

RESULTS:

The results were based on 34 studies from 34 published articles and 6 online registration trials (6710 patients). According to pairwise meta-analysis, PI3K/AKT inhibitors showed to be highly effective, especially for treating mutant cancers, but had poor safety profiles. According to our network meta-analysis, PI3K/AKT inhibitors, especially the AKT inhibitor capivasertib, are effective for treating solid cancers such as breast cancer (BC). Moreover, PI3K inhibitors, especially idelalisib, were effective for treating hematologic cancers such as chronic lymphocytic leukemia (CLL).

CONCLUSIONS:

The PI3K/AKT inhibitors are effective in patients with genetic mutations. For solid cancers such as BC, capivasertib was efficacy and safety. For hematological cancers represented by CLL, idelalisib was efficacy and safety. The above studies can be used when recommending appropriate targeted therapies for patients with different cancer types.

100 项与 SF-2558HA 相关的药物交易

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