AIMSDLGAP5 plays a significant role in promoting cancer progression across various cancers. However, the specific role of DLGAP5 in neuroendocrine differentiation (NED) of prostate cancer (PCa) remains elusive. Our objective is to explore the mechanism by which DLGAP5 mediates NED in PCa.MATERIALS AND METHODSUtilizing diverse public databases, we conducted bioinformatics analysis to examine DLGAP5 expression in PCa. We confirmed aberrant DLGAP5 expression in various PCa cell lines through Western blotting. Functional assays both in vivo and in vitro have validated the oncogenic role of DLGAP5 in PCa. Furthermore, we sought to identify downstream key genes to elucidate the mechanisms underlying DLGAP5-mediated NED in PCa. We also identified a small molecule drug, AAPK-25, which specifically targets DLGAP5.KEY FINDINGSDLGAP5 was highly expressed in NEPC. The suppression of AR signaling promoted DLGAP5 transcription. DLGAP5 endowed PCa cells with a robust ability to proliferate and migrate. E2F1 was an important downstream target of DLGAP5. DLGAP5 mediated the NED of PCa through E2F1. AAPK-25, as an inhibitor of DLGAP5, inhibited PRAD proliferation by repressing the DLGAP5/E2F1 axis both in vitro and in vivo.SIGNIFICANCEWe identified the AR/DLGAP5/E2F1 signaling pathway as a pivotal mechanism that facilitates the transition of PCa towards a neuroendocrine phenotype. This pathway may represent a promising therapeutic target for NEPC patients.

12 Sep 2019·Journal of Medicinal ChemistryQ1 · MEDICINE

Discovery of Inhibitors of Aurora/PLK Targets as Anticancer Agents

Q1 · MEDICINE

Article

Author: He, Jun ; Guo, Xiaoqiang ; Lin, Yao-Xin ; Zhang, Chengchen ; Zhang, Hongjia ; Wang, Ting ; Shi, Jianyou ; Zhong, Ling ; Qi, Baowen ; Li, Rui ; Li, Fengqiong ; Zou, Jing

Aurora and polo-like kinases control the G2/M phase in cell mitosis, which are both considered as crucial targets for cancer cell proliferations. Here, naphthalene-based Aurora/PLK coinhibitors as leading compounds were designed through in silico approach, and a total of 36 derivatives were synthesized. One candidate (AAPK-25) was selected under in vitro cell based high throughput screening with an IC₅₀ value = 0.4 μM to human colon cancer cell HCT-116. A kinome scan assay showed that AAPK-25 was remarkably selective to both Aurora and PLK families. The relevant genome pathways were also depicted by microarray based gene expression analysis. Furthermore, validated from a set of in vitro and in vivo studies, AAPK-25 significantly inhibited the development of the colon cancer growth and prolonged the median survival time at the end of the administration (p < 0.05). To sum up, AAPK-25 has a great potential to be developed for a chemotherapeutic agent in clinical use.

100 Deals associated with AAPK-25

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Colonic Cancer	Discovery	China	University of Electronic Science & Technology of China	12 Sep 2019

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

AAPK-25

Overview

Basic Info

Structure/Sequence

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation