ArticleJournal of immunology (Baltimore, Md. : 1950)2010
Novel SHP-1 inhibitors tyrosine phosphatase inhibitor-1 and analogs with preclinical anti-tumor activities as tolerated oral agents.
Article in Journal of immunology (Baltimore, Md. : 1950), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 69 citations in OpenAlex.
- Recent Advances in Research on SHP Family Phosphatases: Signal Regulation Mechanisms and Disease Associations.Cell biochemistry and function · 2026Review
- The role of classical protein tyrosine phosphatases in diabetic kidney disease and therapeutic implications.Journal of biomedical science · 2026Review
- Phosphoproteomic analysis of successive Jurkat CD19-CAR generations reveals TCRζ-driven signalling.Cellular signalling · 2026Article
- Loss of SHP-1 in CD11cFrontiers in immunology · 2026Article
- CD47 inhibits phagocytosis through Vav dephosphorylation.The Journal of cell biology · 2025Article
- Targeting SHP-1 to alleviate testicular inflammation and apoptosis in a Poly(I:C)-induced orchitis model.European journal of medical research · 2025Article
- NC410, a bivalent LAIR-2 construct, remodels collagen in the tumor microenvironment and abrogates neutrophil-driven T cell suppression.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- SHP1 and its downstream p38/SP1/PI3K/YAP/Notch-1 signaling in trophoblast cells suppressed the progression of Preeclampsia via inhibiting proliferation of SMCs.Scientific reports · 2025Article
- Shp-1 regulates the activity of low-affinity T cells specific to endogenous self-antigen during melanoma tumor growth and drives resistance to immune checkpoint inhibition.Journal for immunotherapy of cancer · 2025Article
- SHP-1 inhibition targets leukaemia stem cells to restore immunosurveillance and enhance chemosensitivity by metabolic reprogramming.Nature cell biology · 2024Article
- Signaling-biophysical modeling unravels mechanistic control of red blood cell phagocytosis by macrophages in sickle cell disease.PNAS nexus · 2024Article
- Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders.Nature reviews. Drug discovery · 2023Review
- Small molecule inhibitors for cancer immunotherapy and associated biomarkers - the current status.Frontiers in immunology · 2023Review
- Biomimetic and Materials-Potentiated Cell Engineering for Cancer Immunotherapy.Pharmaceutics · 2022Review
- Cluster analysis of splenocyte microRNAs in the pig reveals key signal regulators of immunomodulation in the host during acute and chronic Toxoplasma gondii infection.Parasites & vectors · 2022Article
- LAIR-1 acts as an immune checkpoint on activated ILC2s and regulates the induction of airway hyperreactivity.The Journal of allergy and clinical immunology · 2022Article
- Colchicine acts selectively in the liver to induce hepatokines that inhibit myeloid cell activation.Nature metabolism · 2021Article
- Macrophage-Targeted Single Walled Carbon Nanotubes Stimulate Phagocytosis via pH-dependent Drug Release.Nano research · 2021Article
- Strategy for Leukemia Treatment Targeting SHP-1,2 and SHIP.Frontiers in cell and developmental biology · 2021Review
- Runx proteins mediate protective immunity against Leishmania donovani infection by promoting CD40 expression on dendritic cells.PLoS pathogens · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Src homology region 2 domain-containing phosphatase 1 (SHP-1) has been implicated as a potential cancer therapeutic target by its negative regulation of immune cell activation and the activity of the SHP-1 inhibitor sodium stibogluconate that induced IFN-gamma(+) cells for anti-tumor action. To develop more potent SHP-1-targeted anti-cancer agents, inhibitory leads were identified from a library of 34,000 drug-like compounds. Among the leads and active at low nM for recombinant SHP-1, tyrosine phosphatase inhibitor-1 (TPI-1) selectively increased SHP-1 phospho-substrates (pLck-pY394, pZap70, and pSlp76) in Jurkat T cells but had little effects on pERK1/2 or pLck-pY505 regulated by phosphatases SHP-2 or CD45, respectively. TPI-1 induced mouse splenic-IFN-gamma(+) cells in vitro, approximately 58-fold more effective than sodium stibogluconate, and increased mouse splenic-pLck-pY394 and -IFN-gamma(+) cells in vivo. TPI-1 also induced IFN-gamma(+) cells in human peripheral blood in vitro. Significantly, TPI-1 inhibited ( approximately 83%, p < 0.002) the growth of B16 melanoma tumors in mice at a tolerated oral dose in a T cell-dependent manner but had little effects on B16 cell growth in culture. TPI-1 also inhibited B16 tumor growth and prolonged tumor mice survival as a tolerated s.c. agent. TPI-1 analogs were identified with improved activities in IFN-gamma(+) cell induction and in anti-tumor actions. In particular, analog TPI-1a4 as a tolerated oral agent completely inhibited the growth of K1735 melanoma tumors and was more effective than the parental lead against MC-26 colon cancer tumors in mice. These results designate TPI-1 and the analogs as novel SHP-1 inhibitors with anti-tumor activity likely via an immune mechanism, supporting SHP-1 as a novel target for cancer treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.