2-(2-nitrobenzylidene) indolin-3-one compound inhibits transmembrane prostate androgen-induced protein (TMEPAI)

Yuyin Li1, Jianjun Wang1, Ning Song1

  • 1Key Lab of Industrial Fermentation Microbiology of the Ministry of Education, School of Biotechnology, Tianjin University of Science and Technology, Tianjin, China.

Cell Proliferation
|August 3, 2018
PubMed
Abstract

Insights

A novel compound, JHY-A007-50, effectively inhibits the transmembrane prostate androgen-induced protein (TMEPAI) and suppresses cancer cell proliferation. This discovery offers a potential new therapeutic strategy for cancer treatment targeting TMEPAI.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Aberrant expression of transmembrane prostate androgen-induced protein (TMEPAI) is implicated in tumorigenesis.
  • TMEPAI represents a potential therapeutic target for cancer drug discovery.

Purpose of the Study:

  • To screen for compounds that inhibit TMEPAI expression.
  • To evaluate the effects of identified inhibitors on cancer cell proliferation.

Main Methods:

  • A firefly luciferase reporter assay was used to screen for TMEPAI inhibitors.
  • Cancer cell proliferation was assessed via colony formation, cell cycle analysis, Ki-67 immunofluorescence, and EdU incorporation assays.

Main Results:

  • 2-(2-nitrobenzylidene) indolin-3-one (JHY-A007-50) was identified as a potent inhibitor of TMEPAI promoter activity.
  • JHY-A007-50 suppressed TMEPAI expression at both mRNA and protein levels, inhibited cancer cell proliferation, and induced G1 phase cell cycle arrest.
  • Overexpression of TMEPAI reduced the inhibitory effects of JHY-A007-50, confirming TMEPAI's role in mediating the compound's action.

Conclusions:

  • Compound JHY-A007-50 effectively downregulates TMEPAI expression.
  • JHY-A007-50 demonstrates significant potential in inhibiting cancer cell proliferation, highlighting its therapeutic promise.

Related Concept Videos

ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH301:11

ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH3

All ortho–para directors, excluding halogens, are activating groups. These groups donate electrons to the ring, making the ring carbons electron-rich. Consequently, the reactivity of the aromatic ring towards electrophilic substitution increases. For instance, the nitration of anisole is about 10,000 times faster than the nitration of benzene. The electron-donating effect of the methoxy group in anisole activates the ortho and para positions on the ring and stabilizes the corresponding...
7.5K
meta-Directing Deactivators: –NO2, –CN, –CHO, –⁠CO2R, –COR, –CO2H01:13

meta-Directing Deactivators: –NO2, –CN, –CHO, –⁠CO2R, –COR, –CO2H

All meta-directing substituents are deactivating groups. These substituents withdraw electrons from the aromatic ring, making the ring less reactive toward electrophilic substitution. For example, the nitration of nitrobenzene is 100,000 times slower than that of benzene because of the deactivating effect of the nitro group. The first step in an electrophilic aromatic substitution is the addition of an electrophile to form a resonance-stabilized carbocation. The energy diagrams for...
6.7K
2° Amines to N-Nitrosamines: Reaction with NaNO201:20

2° Amines to N-Nitrosamines: Reaction with NaNO2

Secondary amines react with nitrous acid to form N-nitrosamines, as depicted in Figure 1. Nitrous acid, a weak and unstable acid, is formed in situ from an aqueous solution of sodium nitrite and strong acids, such as hydrochloric acid or sulfuric acid, in cold conditions. In the presence of an acid, the nitrous acid gets protonated. The subsequent loss of water results in the formation of the electrophile known as nitrosonium ion.
5.5K
Single-pass Transmembrane Proteins01:25

Single-pass Transmembrane Proteins

Integral membrane proteins are tightly associated with the cell membrane and play a crucial role in cell communication, signaling, adhesion, and transport of the molecules. Some integral membrane proteins are present only in the membrane monolayer. For example, the enzyme fatty acid amide hydrolase is present in the cytoplasmic side of the membrane monolayer. In contrast, another type of integral membrane protein, also known as a transmembrane protein, spans across the membrane. Transmembrane...
6.7K
SN2 Reaction: Kinetics02:14

SN2 Reaction: Kinetics

Kinetic Studies and Significance
In a chemical reaction, a relationship exists between the concentration of reactants and the rate at which the reaction proceeds. The study to measure this relationship is known as the kinetics of a chemical reaction. Kinetic studies are used to deduce the rate law of a chemical reaction, which provides information about the species involved during the transition state of the rate-determining step. Thus, kinetic studies help to derive the mechanism of a...
10.3K
SN2 Reaction: Mechanism02:27

SN2 Reaction: Mechanism

The kinetic studies of SN2 reactions suggest an essential feature of its mechanism: it is a single-step process without intermediates. Here, both the nucleophile and the substrate participate in the rate-determining step.
The presence of the more electronegative halogen in the substrate creates a polarized carbon-halide bond. The halide pulls the electron cloud generating an electrophilic center at the carbon atom. Thus, the carbon atom carries a partial positive charge while the halide has a...
17.5K