Delving into the Latest Updates on MCM2 inhibitors with Synapse

Overview

Basic Info

Drug Type

Oligonucleotide

Synonyms

miR‑370‑3p

Target

MCM2

Action

inhibitors

Mechanism

MCM2 inhibitors(minichromosome maintenance complex component 2 inhibitors)

Therapeutic Areas-

Active Indication-

Inactive Indication-

Originator Organization

Foshan Inte Pharmaceutical Technology Co., Ltd.

Active Organization-

Inactive Organization

Foshan Inte Pharmaceutical Technology Co., Ltd.

Drug Highest PhasePendingDiscovery

First Approval Date-

Regulation-

Structure/Sequence

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Molecular dynamics simulation was performed to identify active pockets in the MCM2 protein structure (6EYC). The active pocket was used as a docking model to discover MCM2 inhibitors by using structure-based virtual screening and surface plasmon resonance (SPR) assay. Furthermore, the efficacy of pixantrone targeting MCM2 in ovarian cancer was evaluated in vitro and in vivo.

RESULTS:

Pixantrone was identified as a novel inhibitor of MCM2 by virtual screening. SPR binding affinity analysis confirmed the direct binding of pixantrone to MCM2 protein. Pixantrone significantly reduced the viability of ovarian cancer cells A2780 and SKOV3 in a dose- and time-dependent manner. In addition, pixantrone inhibited DNA replication, and induced cell cycle arrest and apoptosis in ovarian cancer cells via targeting MCM2. Knockdown of MCM2 could attenuate the inhibitory activity of pixantrone in ovarian cancer cells. Furthermore, pixantrone significantly suppressed ovarian cancer growth in the A2780 cell xenograft mouse model and showed favorable safety.

CONCLUSION:

These findings suggest that pixantrone may be a promising drug for ovarian cancer patients by targeting MCM2 in the clinic.

01 Jun 2023·Immunity, inflammation and disease

Circ_0035292 knockdown alleviates lipopolysaccharide (LPS)‐induced WI‐38 cell apoptosis and inflammatory injury

Article

Author: Cheng, Chen ; Li, Zhouzhen ; Guo, Ying

Abstract:

Background:

Circular RNAs have emerged as important regulators in the pathogenesis of human diseases, including infantile pneumonia (IP). In this study, we aimed to explore the effects of circ_0035292 on lipopolysaccharide (LPS)‐treated Wistsar Institute (WI)‐38 cells.

Methods:

Quantitative real‐time polymerase chain reaction and western blot were executed to detect the levels of circ_0035292, microRNA‐370‐3p (miR‐370‐3p) and transducin β‐like 1X related protein 1 (TBL1XR1). Cell counting kit‐8, 5‐ethynyl‐2′‐deoxyuridine, and flow cytometry assessed cell proliferation and apoptosis. Concentrations of inflammatory factors were examined with enzyme linked immunosorbent assay kits. Dual‐luciferase reporter assay and RNA immunoprecipitation were adopted to analyze binding between miR‐370‐3p and circ_0035292 or TBL1XR1.

Results:

Circ_0035292 level was increased in IP patients and LPS‐triggered WI‐38 cells. Circ_0035292 knockdown rescued LPS‐mediated WI‐38 cell proliferation suppression and WI‐38 cell apoptosis and inflammation promotion. Circ_0035292 interacted with miR‐370‐3p and miR‐370‐3p directly targeted TBL1XR1. Moreover, miR‐370‐3p overexpression alleviated LPS‐induced WI‐38 cell apoptosis and inflammatory injury, which was abrogated via TBL1XR1 upregulation. Circ_0035292 absence inhibited the NF‐κB pathway.

Conclusion:

Knockdown of circ_0035292 rescued LPS‐triggered WI‐38 cell injury via miR‐370‐3p/TBL1XR1 axis and NF‐κB pathway.

01 Jun 2021·Cell biology internationalQ4 · BIOLOGY

MiR‐370‐3p inhibits the development of human endometriosis by downregulating EDN1 expression in endometrial stromal cells

Q4 · BIOLOGY

Article

Author: Huang, Chengyi ; Wang, Wei ; Zhou, Shun ; Liu, Juan

Abstract:

MiR‐370‐3p has been demonstrated to be downregulated in patients with endometriosis (EM). However, its role and molecular mechanisms in the progression of EM remain unclear. Real‐time polymerase chain reaction was used to measure the expression of miR‐370‐3p and endothelin‐1 (EDN1) in patients with or without EM. After miR‐370‐3p overexpression or knockdown in ectopic endometrial hEM15A cells, the changes in the proliferation, apoptosis, and migration and invasion capacities were detected by using cell counting kit‐8, flow cytometry, and transwell methods. The interplay between miR‐370‐3p and EDN1 was confirmed by a luciferase reporter assay. Patients with EM showed adverse expression of EDN1 and miR‐370‐3p, especially in eutopic endometrium and ectopic endometrium. MiR‐370‐3p inhibited the proliferation, metastasis, and invasion capacities of hEM15A cells and promoted apoptosis. Investigation of its molecular mechanism revealed that miR‐370‐3p targeted EDN1 to influence the biological functions of hEM15A cells. MiR‐370‐3p represented as a therapeutic target for EM treatment.

100 Deals associated with MCM2 inhibitors

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