Protein tyrosine phosphatase non-receptor type 1 (PTPN1)
Protein tyrosine phosphatase non-receptor type 1 (PTPN1), commonly known as protein tyrosine phosphatase 1B (PTP1B), is a non-receptor protein tyrosine phosphatase that functions as a key negative regulator of signaling pathways mediated by receptor tyrosine kinases.
Protein tyrosine phosphatase non-receptor type 1 (PTPN1), commonly known as protein tyrosine phosphatase 1B (PTP1B), is a non-receptor protein tyrosine phosphatase that functions as a key negative regulator of signaling pathways mediated by receptor tyrosine kinases. In the contexts provided, it is described as a major modulator of insulin and Leptin (LEP) signaling, and therefore as an important molecular target in type 2 diabetes, obesity, and broader metabolic dysfunction. By attenuating these pathways, PTP1B can contribute to insulin resistance and impaired metabolic homeostasis.
Recent research also highlights a more complex role for PTP1B in immune and inflammatory biology. In myeloid cells, it has been linked to monocyte and macrophage activation, with implications for diabetic retinopathy and retinal neurodegeneration. This broader biology has made PTP1B a continuing focus of drug discovery efforts, especially for selective inhibitors that could improve glucose homeostasis and metabolic signaling without unacceptable off-target effects.
Where the papers sit
12 papers from the last 6 months study Protein tyrosine phosphatase non-receptor type 1 (PTPN1) directly · updated from PubMed 7 Oct 2026
Study type 0 clinical trials · 2 human data · 10 preclinical
Themes 3 themes · 2 new directions
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Phosphatase Signaling in Cancer
SHP2 and PTP1B inhibition is being explored as a way to disrupt RAS-linked cancer signaling and tumor growth. Allosteric inhibitors such as I-0436650 and NSC 57774 act across EGFR, STAT3 and related pathways, while PI3K signaling emerges as a route to KRAS-inhibitor resistance. The work also links PTP1B blockade to multi-mechanistic antiproliferative and redox effects. Translational priorities remain selective compounds and better control of pathway-specific resistance.
6 papers · 50%
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Tyrosine Phosphatase Therapeutics
Tyrosine phosphatases are being pursued both as disease drivers and as tractable drug targets. PTP1B contributes to diabetic retinal neurodegeneration, while PTPN11-linked leukemia is approached through GLP-1R and IL-17A modulation. Chemical efforts are expanding from selective PTPN2/N1 inhibitors to noninhibitory macrocyclic ligands and proximity-oriented therapeutic designs. The central open question is whether selectivity and tissue targeting can convert these mechanisms into safer treatments.
4 papers · 33.3%
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Dual DPP-4 and PTP1B Inhibition
Dual inhibition of DPP-4 and PTP1B is emerging as the shared strategy for metabolic drug discovery in this cluster. Structure-based design seeks compounds that engage both enzymes, while Achillea biserrata extracts and chlorogenic-acid-rich fractions provide natural-product leads with antioxidant activity. The work remains at the biochemical and preclinical screening stage, emphasizing potency, selectivity and target-enzyme validation. Whether dual activity improves metabolic efficacy over single-target inhibition remains unresolved.
2 papers · 16.7%
PTPN1 is identified as a myeloid-cell driver of diabetic retinal neurodegeneration
The diabetic-mouse retinal-neurodegeneration study 42166617May moves PTPN1 beyond the set’s usual framing as a metabolic regulator or tumor-cell therapeutic target by assigning it a causal, cell-specific role in diabetic retinal injury. Myeloid-specific PTPN1 depletion and pharmacological inhibition both prevented streptozotocin-induced retinal neurodegeneration, indicating that PTPN1-dependent macrophage and leukocyte responses can drive neural damage in the diabetic retina rather than merely modulate systemic metabolism or tumor-cell proliferation.
PTPN1 is positioned as a regulator of interferon-γ signaling and antitumor T-cell activity
The benzothiophene difluoromethyl-phosphonate PTPN1/PTPN2 inhibitor study 42054654Apr gives PTPN1 an immuno-oncology role outside the metabolic and tumor-intrinsic signaling categories used elsewhere in the set. Its authors treat PTPN1 inhibition as a means of modulating interferon-γ signaling and T-cell activity, and compound 25 produced dose-dependent pSTAT1 induction in MC38 tumors, shifting PTPN1 from a target for correcting insulin or leptin resistance or directly suppressing cancer cells to a target for enhancing antitumor immune signaling.
Papers
The 12 papers from the last 6 months that study Protein tyrosine phosphatase non-receptor type 1 (PTPN1) directly, newest first, by theme and by study type. Study types come from PubMed publication types and MeSH headings.
By theme
Phosphatase Signaling in Cancer (6)
- Multi-Omics and Computational Pharmacology Approach With Experimental Validation Reveals the Antiproliferative Activity of Sophoricoside Against Pancreatic Cancer. Chemistry & biodiversity · 30 Sept 2026 PMID 42814531
- Discovery and Preclinical Characterization of I-0436650, a Selective SHP2 Allosteric Inhibitor for RAS-Driven Cancers. Journal of medicinal chemistry · 13 Aug 2026 PMID 42593923
- Mechanistic evaluation of NSC 57774 as a SHP2 inhibitor in gastric cancer: Multi-pathway signaling modulation in vitro. PloS one · 30 Jul 2026 PMID 42531194
- Allosteric PTP1B inhibition as a source of multi-mechanistic anti-tumor activity. Bioorganic chemistry · 19 Jun 2026 PMID 42320116
- Flavonoids from Elsholtzia ciliata restore redox electron flow and metabolic signaling via PTP1B inhibition in muscle and liver cells. Journal of enzyme inhibition and medicinal chemistry · 11 May 2026 PMID 42113121
- PI3K Regulates Wild-type RAS Signaling to Confer Resistance to KRAS Inhibition. Cancer research · 7 May 2026 PMID 42095550
Tyrosine Phosphatase Therapeutics (4)
- Discovery of Noninhibitory Macrocyclic Ligands for Protein Tyrosine Phosphatase 1B Using a Function-Based, Iterative Screening Strategy. Journal of the American Chemical Society · 27 Jul 2026 PMID 42504525
- Targeting GLP-1R and IL-17A suppresses obesity-induced leukemia in an oncogenic PTPN11 mutation-driven model. The Journal of clinical investigation · 23 Jun 2026 PMID 42334870
- Myeloid Cell Protein Tyrosine Phosphatase 1B Drives Retinal Neurodegeneration in Diabetic Mice. Diabetes · 21 May 2026 PMID 42166617
- Discovery of Potent and Selective Benzothiophene Difluoromethyl Phosphonate (DFMP) PTPN2/N1-Dual Inhibitors. Journal of medicinal chemistry · 29 Apr 2026 PMID 42054654
Dual DPP-4 and PTP1B Inhibition (2)
- Bioactive Properties of Achillea biserrata M.Bieb. Extracts: Phytochemical Analysis, Antioxidant Activity, Target Enzyme Inhibition, and Cytotoxic Effects. Chemistry & biodiversity · 31 Aug 2026 PMID 42672901
- Structure-Based De Novo Design of Novel Dual DPP IV and PTP 1B Inhibitors (DDPI's). Chemistry & biodiversity · 30 Jun 2026 PMID 42378400
By study type
Human data, design not indexed (2)
- Discovery of Noninhibitory Macrocyclic Ligands for Protein Tyrosine Phosphatase 1B Using a Function-Based, Iterative Screening Strategy. Journal of the American Chemical Society · 27 Jul 2026 PMID 42504525
- Structure-Based De Novo Design of Novel Dual DPP IV and PTP 1B Inhibitors (DDPI's). Chemistry & biodiversity · 30 Jun 2026 PMID 42378400
Preclinical: animal, cell and lab studies (10)
- Multi-Omics and Computational Pharmacology Approach With Experimental Validation Reveals the Antiproliferative Activity of Sophoricoside Against Pancreatic Cancer. Chemistry & biodiversity · 30 Sept 2026 PMID 42814531
- Bioactive Properties of Achillea biserrata M.Bieb. Extracts: Phytochemical Analysis, Antioxidant Activity, Target Enzyme Inhibition, and Cytotoxic Effects. Chemistry & biodiversity · 31 Aug 2026 PMID 42672901
- Discovery and Preclinical Characterization of I-0436650, a Selective SHP2 Allosteric Inhibitor for RAS-Driven Cancers. Journal of medicinal chemistry · 13 Aug 2026 PMID 42593923
- Mechanistic evaluation of NSC 57774 as a SHP2 inhibitor in gastric cancer: Multi-pathway signaling modulation in vitro. PloS one · 30 Jul 2026 PMID 42531194
- Targeting GLP-1R and IL-17A suppresses obesity-induced leukemia in an oncogenic PTPN11 mutation-driven model. The Journal of clinical investigation · 23 Jun 2026 PMID 42334870
- Allosteric PTP1B inhibition as a source of multi-mechanistic anti-tumor activity. Bioorganic chemistry · 19 Jun 2026 PMID 42320116
- Myeloid Cell Protein Tyrosine Phosphatase 1B Drives Retinal Neurodegeneration in Diabetic Mice. Diabetes · 21 May 2026 PMID 42166617
- Flavonoids from Elsholtzia ciliata restore redox electron flow and metabolic signaling via PTP1B inhibition in muscle and liver cells. Journal of enzyme inhibition and medicinal chemistry · 11 May 2026 PMID 42113121
- PI3K Regulates Wild-type RAS Signaling to Confer Resistance to KRAS Inhibition. Cancer research · 7 May 2026 PMID 42095550
- Discovery of Potent and Selective Benzothiophene Difluoromethyl Phosphonate (DFMP) PTPN2/N1-Dual Inhibitors. Journal of medicinal chemistry · 29 Apr 2026 PMID 42054654
Written from 12 PubMed abstracts, each one listed by PMID above. Published: 2026-07-08. Last written: 2026-09-02 by GPT. Drafted by language models from published abstracts; not medical advice.