Dataset Information

Artificial intelligence-driven new drug discovery targeting serine/threonine kinase 33 for cancer treatment.

ABSTRACT:

Background

Artificial intelligence (AI) is capable of integrating a large amount of related information to predict therapeutic relationships such as disease treatment with known drugs, gene expression, and drug-target binding. AI has gained increasing attention as a promising tool for next-generation drug development.

Methods

An AI method was used for drug repurposing and target identification for cancer. Among 8 survived candidates after background checking, N-(1-propyl-1H-1,3-benzodiazol-2-yl)-3-(pyrrolidine-1-sulfonyl) benzamide (Z29077885) was newly selected as an new anti-cancer drug, and the anti-cancer efficacy of Z29077885 was confirmed using cell viability, western blot, cell cycle, apoptosis assay in MDA-MB 231 and A549 in vitro. Then, anti-tumor efficacy of Z29077885 was validated in an in vivo A549 xenograft in BALB/c nude mice.

Results

First, we discovered an antiviral agent, Z29077885, as a new anticancer drug candidate using the AI deep learning method. Next, we demonstrated that Z29077885 inhibits Serine/threonine kinase 33 (STK33) enzymatic function in vitro and showed the anticancer efficacy in various cancer cells. Then, we found enhanced apoptosis via S-phase cell cycle arrest as the mechanism underlying the anticancer efficacy of Z29077885 in both lung and breast cancer cells. Finally, we confirmed the anti-tumor efficacy of Z29077885 in an in vivo A549 xenograft.

Conclusions

In this study, we used an AI-driven screening strategy to find a novel anticancer medication targeting STK33 that triggers cancer cell apoptosis and cell cycle arrest at the s phase. It will pave a way to efficiently discover new anticancer drugs.

SUBMITTER: Tran NL

PROVIDER: S-EPMC10717841 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Artificial intelligence-driven new drug discovery targeting serine/threonine kinase 33 for cancer treatment.

Tran Na Ly NL Kim Hyerim H Shin Cheol-Hee CH Ko Eun E Oh Seung Ja SJ

Cancer cell international 20231212 1

<h4>Background</h4>Artificial intelligence (AI) is capable of integrating a large amount of related information to predict therapeutic relationships such as disease treatment with known drugs, gene expression, and drug-target binding. AI has gained increasing attention as a promising tool for next-generation drug development.<h4>Methods</h4>An AI method was used for drug repurposing and target identification for cancer. Among 8 survived candidates after background checking, N-(1-propyl-1H-1,3-be ...[more]

PMID: 38087254

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Dataset Information

Artificial intelligence-driven new drug discovery targeting serine/threonine kinase 33 for cancer treatment.

Background

Methods

Results

Conclusions

Publications

Artificial intelligence-driven new drug discovery targeting serine/threonine kinase 33 for cancer treatment.

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