Related Experiment Video
Updated: Mar 9, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
In silico selection and cell-based characterization of selective and bioactive compounds for androgen-dependent
Elisa C Santa Cruz1, Adriel R Carecho1, Marta E Saidel1
1Medicinal Chemistry Group (NEQUIMED), São Carlos Institute of Chemistry (IQSC), University of São Paulo (USP), Av. Trabalhador São-carlense, 400, São Carlos, SP 13566-590, Brazil.
Abstract:
Prostate cancer is one of the most prevalent types of cancer in male population. It is a hormone driven disease, especially in its initial phase. Hence, androgen deprivation therapy (ADT) is the major chemotherapeutic effort and novel AR inhibitors with improved pharmacological profiles are needed. In this report, a novel bioactive compound was selected and investigated using in silico and cell-based assays. Neq0502 compound was selective for the testosterone stimulated AR-dependent prostate cancer cell (LNCaP, GI50=22.4μM) when compared with unstimulated LNCaP or AR-insensitive (DU145 and PC-3) cell lines. Cell cycle arrest study provided the same profile for Neq0502 and the reference drug enzalutamide. Moreover, this compound is not cytotoxic for fibroblast Balb/C 3T3 clone A31 cells up to 250μM, with a good selectivity ratio (SI>11), which could be used in compound optimization effort to a novel therapeutic alternative.
Insights
A novel compound, Neq0502, shows selective inhibition of androgen receptor (AR) in prostate cancer cells. This compound offers a potential new therapeutic alternative for hormone-driven prostate cancer treatment.
Area of Science:
- Oncology
- Pharmacology
Background:
- Prostate cancer is a prevalent, hormone-driven malignancy.
- Androgen deprivation therapy (ADT) is a primary treatment, necessitating novel androgen receptor (AR) inhibitors.
Purpose of the Study:
- To investigate the efficacy and selectivity of a novel bioactive compound, Neq0502.
- To evaluate Neq0502 as a potential therapeutic agent for prostate cancer.
Main Methods:
- In silico and cell-based assays were employed.
- Compound selectivity was assessed against AR-dependent (LNCaP) and AR-insensitive (DU145, PC-3) prostate cancer cell lines.
- Cell cycle arrest and cytotoxicity assays were performed.
Main Results:
- Neq0502 demonstrated selectivity for testosterone-stimulated AR-dependent LNCaP cells (GI50=22.4μM).
- The compound induced cell cycle arrest, similar to the reference drug enzalutamide.
- Neq0502 exhibited low cytotoxicity in fibroblast cells (SI>11), indicating good selectivity.
Conclusions:
- Neq0502 is a selective AR inhibitor with potential therapeutic value.
- The compound's profile supports its further optimization for novel prostate cancer therapies.
