PPA24(PPA24) - 药物靶点：PP2A_在研适应症：黑色素瘤，结肠癌_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

PP2A

作用机制

PP2A刺激剂(蛋白质磷酸酶2A刺激剂)

治疗领域

肿瘤消化系统疾病皮肤和肌肉骨骼疾病

在研适应症

黑色素瘤结肠癌

非在研适应症-

原研机构

Penn State Hershey College of Medicine

在研机构

Penn State Hershey College of Medicine

非在研机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C22H27BrClN5S

InChIKeyUXJLBJDEPANSAH-UHFFFAOYSA-M

CAS号3035032-77-7

关联

100 项与 PPA24 相关的临床结果

登录后查看更多信息

100 项与 PPA24 相关的转化医学

登录后查看更多信息

100 项与 PPA24 相关的专利（医药）

登录后查看更多信息

1

项与 PPA24 相关的文献（医药）

2024-10-24·Journal of Medicinal Chemistry

Identification of a Novel Protein Phosphatase 2A Activator, PPA24, as a Potential Therapeutic for FOLFOX-Resistant Colorectal Cancer

Article

作者: Sha, Congzhou M. ; Sharma, Arun K. ; Dokholyan, Nikolay V. ; Johnson, Hannah ; Singh, Amandeep ; Nair, Haritha ; Wang, Jian ; Raza, Asif ; Li, Chenglong ; Shen, Zhihang ; Narayan, Satya ; Gowda, Krishne

A series of compounds were designed utilizing molecular modeling and fragment-based design based upon the known protein phosphatase 2A (PP2A) activators, NSC49L and iHAP1, and evaluated for their ability to inhibit the viability of colorectal cancer (CRC) and folinic acid, 5-fluorouracil, and oxaliplatin (FOLFOX)-resistant CRC cells. PPA24 (19a) was identified as the most cytotoxic compound with IC₅₀ values in the range of 2.36-6.75 μM in CRC and FOLFOX-resistant CRC cell lines. It stimulated PP2A activity to a greater extent, displayed lower binding energies through molecular docking, and showed higher binding affinity through surface plasmon resonance for PP2A catalytic subunit α than the known PP2A activators. PPA24 dose-dependently induced apoptosis and oxidative stress, decreased the level of c-Myc expression, and synergistically potentiated cytotoxicity when combined with gemcitabine and cisplatin. Furthermore, a PPA24-encapsulated nanoformulation significantly inhibited the growth of CRC xenografts without systemic toxicities. Together, these results signify the potential of PPA24 as a novel PP2A activator and a prospective therapeutic for CRC and FOLFOX-resistant CRC.

100 项与 PPA24 相关的药物交易

登录后查看更多信息