The EZMTT cell proliferation assay provides precise measurement for drug combinations and better correlation between in vitro and in vivo efficacy.

Bioorg Med Chem Lett

College of Pharmaceutical Science, Collaborative Innovation Center of Yangtza River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China. Electronic address:

Published: June 2020

The rate of drug-induced proliferation (DIP) has been proposed as an unbiased alternative drug effect metric. However, current assays are not easy and precise enough to track minor changes in cell growth. Here, we report the optimized EZMTT based detection method which can continuously measure time-dependent growth after drug treatment and reliably detect partial drug resistance for cancer cells. Importantly, tracking time-dependent growth after drug treatment demonstrated that a KGA allosteric inhibitor alone failed to completely inhibit cancer cell growth, but a drug combination was able to provide complete inhibition in cell-based assays that translated well in in vivo animal experiments. In conclusion, this simple EZMTT method provided precise measurement of loss of susceptibility after drug treatment and has great potential to be developed for drug efficacy and drug combination studies to solve the unmet medical need.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmcl.2020.127134DOI Listing

Publication Analysis

Top Keywords

growth drug
12
drug treatment
12
drug
9
precise measurement
8
cell growth
8
time-dependent growth
8
drug combination
8
ezmtt cell
4
cell proliferation
4
proliferation assay
4

Similar Publications

Autophagy in brain tumors: molecular mechanisms, challenges, and therapeutic opportunities.

J Transl Med

January 2025

Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, No. 569 Xinsi Road, Xi'an, China.

Autophagy is responsible for maintaining cellular balance and ensuring survival. Autophagy plays a crucial role in the development of diseases, particularly human cancers, with actions that can either promote survival or induce cell death. However, brain tumors contribute to high levels of both mortality and morbidity globally, with resistance to treatments being acquired due to genetic mutations and dysregulation of molecular mechanisms, among other factors.

View Article and Find Full Text PDF

Targeting lipid metabolism: novel insights and therapeutic advances in pancreatic cancer treatment.

Lipids Health Dis

January 2025

Emergency surgery Dapartment (Trauma center), The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, 471003, Henan, China.

Lipid metabolism in cancer is characterized by dysregulated lipid regulation and utilization, critical for promoting tumor growth, survival, and resistance to therapy. Pancreatic cancer (PC) is a highly aggressive malignancy of the gastrointestinal tract that has a dismal 5-year survival rate of less than 10%. Given the essential function of the pancreas in digestion, cancer progression severely disrupts its function.

View Article and Find Full Text PDF

Background: Most patients with prostate cancer inevitably progress to castration-resistant prostate cancer (CRPC), at which stage chemotherapeutics like docetaxel become the first-line treatment. However, chemotherapy resistance typically develops after an initial period of therapeutic efficacy. Increasing evidence indicates that cancer stem cells confer chemotherapy resistance via exosomes.

View Article and Find Full Text PDF

Background: Colorectal cancer (CRC) is a prevalent malignancy worldwide, associated with significant morbidity and mortality. Cyclin-dependent kinase 1 (CDK1) plays a crucial role in cell cycle regulation and has been implicated in various cancers. This study aimed to evaluate the prognostic value of CDK1 in CRC and to identify traditional Chinese medicines (TCM) that can target CDK1 as potential treatments for CRC.

View Article and Find Full Text PDF

Spermine driven water deficit tolerance in early growth phases of sweet corn genotypes under hydroponic cultivation.

Sci Rep

January 2025

Department of Applied Plant Biology, Faculty of Agricultural and Food Sciences and Environmental Management, University of Debrecen, Debrecen, Hungary.

Sweet corn is highly susceptible to water deprivation, making it crucial to identify effective strategies for enhancing its tolerance to water deficit conditions. This study investigates the novel application of Spermine as a bio-stimulant to improve sweet corn (Zea mays L. var.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!