Related Experiment Video

Updated: Apr 4, 2026

A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors
10:17

A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors

Published on: April 29, 2022

3.0K

Novel inhibitors targeting PPM1D phosphatase potently suppress cancer cell proliferation

Sari Ogasawara1, Yuhei Kiyota1, Yoshiro Chuman1

  • 1Laboratory of Biological Chemistry, Department of Chemistry, Faculty of Science, Hokkaido University, North 10, West 8, Kita-ku, Sapporo 060-0810, Japan.

Bioorganic & Medicinal Chemistry
|September 12, 2015
PubMed

Insights

A novel inhibitor, SL-176, effectively targets PPM1D (Wip1) in breast cancer cells. This compound halts cancer cell proliferation and induces cell death, showing promise for new anti-cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Protein phosphatase magnesium-dependent 1δ (PPM1D, also known as Wip1) is a serine/threonine phosphatase regulated by p53.
  • PPM1D is frequently altered in various cancers, including breast cancer and neuroblastoma, making it a significant therapeutic target.
  • Aberrant PPM1D activity, due to overexpression or mutations, contributes to tumorigenesis.

Purpose of the Study:

  • To investigate the potential of a novel PPM1D inhibitor, SL-176, as an anti-cancer agent.
  • To evaluate the efficacy of SL-176 in inhibiting cancer cell proliferation and inducing cell death.
  • To confirm the specific inhibitory activity of SL-176 against PPM1D in vitro.

Main Methods:

  • Synthesis of the specific PPM1D inhibitor SL-176 through a 10-step process.
  • Treatment of a breast cancer cell line overexpressing PPM1D with SL-176.
  • Assessment of cell proliferation, cell cycle progression (G2/M arrest), and apoptosis.
  • In vitro enzymatic assays to determine PPM1D inhibition potency and specificity.

Main Results:

  • SL-176 significantly inhibited the proliferation of PPM1D-overexpressing breast cancer cells.
  • Treatment with SL-176 induced G2/M cell cycle arrest and apoptosis in cancer cells.
  • SL-176 demonstrated potent and specific inhibition of PPM1D enzyme activity in vitro.
  • The inhibitor SL-176 was synthesized efficiently in 10 steps.

Conclusions:

  • SL-176 is a potent and specific inhibitor of PPM1D (Wip1).
  • SL-176 exhibits anti-proliferative and pro-apoptotic effects in breast cancer cells overexpressing PPM1D.
  • SL-176 represents a promising lead compound for the development of novel anti-cancer therapeutics targeting PPM1D.
Keywords:
Anti-tumorApoptosisDephosphorylationInhibitorsProtein phosphatase

More Related Videos

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

6.8K
Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology07:04

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology

Published on: May 2, 2025

1.3K

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.4K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.2K
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

5.7K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
39.0K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.1K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.9K