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Updated: Jul 17, 2026
Development and Application of Rapamycin-regulated Tyrosine Phosphatases
Published on: September 6, 2024
Establishment of a cell-based drug screening model for identifying down-regulators of Protein Tyrosine Phosphatase 1B
1East China University of Science and Technology, Shanghai, P.R. China. sejiagaseven@163.com
Abstract:
Protein Tyrosine Phosphatase 1B (PTP1B), an important negative regulator of insulin signaling, is thought to be an attractive therapeutic target for insulin resistance and type 2 diabetes. For the aim of screening PTP1B expression down-regulators, we established the drug screening cellular model based on transcriptional regulation of PTP1B. In this study, the promoter sequences of PTP1B were cloned into pGL3B-neo vector containing luciferase gene and neomycin resistance gene. The recombinant reporter gene vector pGL3B-neo /PTP1B was transfected into CV1 cells and therefore stable cell line, namely SPTP1B, was obtained. With the cell-based reporter gene assay, we detected more than one hundred compounds in microtiter wells. In the screening process, the compound CM107 which had extracted from the traditional Chinese medicinal herbs was identified to repress the activity of PTP1B promoter significantly in mode of dose-dependence.
Insights
Researchers screened for compounds that reduce Protein Tyrosine Phosphatase 1B (PTP1B) expression, a key factor in insulin resistance. A novel Chinese herb extract, CM107, was found to significantly inhibit PTP1B promoter activity.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Protein Tyrosine Phosphatase 1B (PTP1B) is a negative regulator of insulin signaling.
- PTP1B is a potential therapeutic target for managing insulin resistance and type 2 diabetes.
Purpose of the Study:
- To establish a cellular model for screening PTP1B expression down-regulators.
- To identify novel compounds that can modulate PTP1B activity.
Main Methods:
- Cloning PTP1B promoter sequences into a pGL3B-neo vector.
- Establishing a stable cell line (SPTP1B) by transfecting CV1 cells with the recombinant reporter gene vector.
- Utilizing a cell-based reporter gene assay to screen compounds.
Main Results:
- Over one hundred compounds were screened using the developed cellular model.
- Compound CM107, derived from traditional Chinese medicinal herbs, was identified as a potent inhibitor.
- CM107 demonstrated significant, dose-dependent repression of PTP1B promoter activity.
Conclusions:
- A robust cell-based reporter gene assay system for PTP1B was successfully established.
- Compound CM107 shows promise as a therapeutic agent for insulin resistance and type 2 diabetes by down-regulating PTP1B.
- Further investigation into CM107's mechanism of action and therapeutic potential is warranted.
