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Updated: Jul 10, 2025

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

6.2K

Small molecule. Big biology. Dual phosphatase inhibitor enters the immunotherapy fray

Nicholas S Wilson1, Nicholas D Huntington2

  • 1Bristol Myers Squibb, Cancer Immunology and Cell Therapy Thematic Research Centre, Redwood City, CL, USA.

Immunology and Cell Biology
|November 20, 2023
PubMed

Insights

A novel dual inhibitor targeting phosphatases PTPN1 and PTPN2 shows preclinical efficacy in cancer models. This discovery offers a new strategy to enhance anti-cancer immune responses by modulating cytokine and T-cell receptor signaling.

Area of Science:

  • Oncology
  • Immunology
  • Pharmacology

Background:

  • Immune checkpoint inhibitors (ICIs) like Ipilimumab, Nivolumab, and Pembrolizumab have transformed cancer treatment.
  • Drug discovery now focuses on both extrinsic targets boosting immune response and intrinsic targets sensitizing cancer cells to immunity.
  • Protein tyrosine phosphatases PTPN1 and PTPN2 (TC-PTP) negatively regulate key immune signaling pathways.

Purpose of the Study:

  • To evaluate the preclinical efficacy of a novel dual inhibitor targeting PTPN1 and PTPN2 in cancer models.
  • To explore a new therapeutic strategy for enhancing anti-cancer immunity.

Main Methods:

  • Development of a first-in-class dual PTPN1/PTPN2 active site inhibitor (ABBV-CLS-484/AC484).
  • Preclinical testing of the inhibitor in relevant cancer models.

Main Results:

  • Demonstration of preclinical efficacy for ABBV-CLS-484/AC484 in cancer models.
  • The dual inhibitor effectively targets PTPN1 and PTPN2, which are negative regulators of immune signaling.

Conclusions:

  • Targeting PTPN1 and PTPN2 with a dual inhibitor represents a promising therapeutic strategy in oncology.
  • This approach has the potential to enhance anti-cancer immune responses and overcome resistance to current therapies.
Keywords:
CD8 T cellsIFNgcancer immunotherapycytokine receptorsphosphatases

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