NDI-101150
NDI-101150 is an orally active, potent and selective hematopoietic progenitor cell kinase 1 (HPK1) inhibitor with an IC50 of 0.7 nM. NDI-101150 blocks HPK1-mediated negative regulation of immune receptor signaling, inhibits immunosuppression of T cell activation, enhances antigen-specific antibody production and augments B-cell activation. NDI-101150 inhibits tumor growth in syngeneic tumor models, establishes durable antitumor immune memory, and synergizes with anti-PD1 to enhance exhausted T cell activity and drive tumor regressions. NDI-101150 can be used for the research of cancer, such as breast cancer and colon cancer.
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- CAS 番号: 2628486-22-4
- 分子式: C27H27FN6O2
- 分子量:486.54
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
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生物活性
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化学情報
- 純度とドキュメンテーション
- 参考文献
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生物活性
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HPK1 0.7 nM (IC50) |
IL-2 |
NDI-101150 potently and selectively inhibits HPK1 in a cell-free biochemical assay with an IC50 of 0.7 nM, and exhibits high fold-selectivity over closely related MAP4K family kinases and immune cell signaling kinases[1].
NDI-101150 potently inhibits HPK1 in a cell-based assay with an IC50 of 41 nM[1].
NDI-101150 (1-10000 nM) reverses TGF-β-, PGE2, TREG, Adenosine (HY-B0228)-induced immunosuppression of human T cells, restoring IFN-γ, IL-2 production to naive T cell levels[1].
NDI-101150 (0.003-1.0 μM) induces dose-dependent increases in IFN-γ, TNF-α, and GM-CSF production in human mixed lymphocyte reactions, with responses surpassing naive T cell levels[1].
NDI-101150 reinvigorates exhausted human T cells, restoring IL-2 secretion after a 10-day stimulation/rest exhaustion protocol[1].
NDI-101150 is a highly potent and selective cell-free inhibitor of HPK1 kinase activity, with an IC50 of 0.7 nM, and exhibits exceptional selectivity over other MAP4K family members and critical immune cell kinases[2].
NDI-101150 dose-dependently inhibits SLP-76 phosphorylation in anti-CD3-stimulated human Jurkat T cells, with an IC50 of 41 nM[2].
NDI-101150 dose-dependently inhibits SLP-76 phosphorylation in anti-CD3-stimulated human CD4+ and CD8+ T cells (IC50 = 21 nM and 20 nM, respectively) without reducing cell viability[2].
NDI-101150 dose-dependently inhibits BLNK phosphorylation in anti-IgM-stimulated human B cells, with an IC50 of 48 nM[2].
NDI-101150 (0.001-1.0 μM; 72-96 h) dose-dependently enhances anti-CD3/CD28-induced cytokine secretion and proliferation in human primary CD4+ and CD8+ T cells, with EC50 values ranging from 11-17 nM for cytokines, and does not reduce cell viability[2].
NDI-101150 (0.0015-3.3 μM) dose-dependently enhances IFN-γ production in human mixed lymphocyte reactions[2].
NDI-101150 (0.03-3.0 μM) dose-dependently enhances anti-IgM-induced CD19+ B-cell activation, IgG secretion, and proliferation[2].
NDI-101150 (1-10000 nM; 24-48 h) dose-dependently restores and enhances T-cell activation in human primary T cells suppressed by TGF-β, PGE2, or Adenosine, with cytokine secretion exceeding naïve T-cell levels at higher concentrations[2].
NDI-101150 (0.003-1.0 μM) dose-dependently reactivates exhausted human T cells in MLRs, inducing proliferation and cytokine secretion, and shows synergistic effects when combined with anti-PD-1[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:CD4+ and CD8+ T cells
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Concentration:0.001, 0.003, 0.01, 0.03, 0.1, 0.3 μM
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Incubation Time:72, 96 h
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Result:Dose-dependently enhanced cell proliferation.
NDI-101150 (75-150 mg/kg; p.o.; once daily for 12-20 days) induces ~40% tumor growth inhibition and enhances proinflammatory cytokine and antibody production in female BALB/c mice with anti-PD-1-resistant syngeneic CT-26 and B16F10 tumors[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c (female, syngeneic EMT-6 tumor model)[2]
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Dosage:75 mg/kg
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Administration:p.o.; once daily; 17 days
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Result:Resulted in ~70% tumor growth inhibition relative to vehicle by day 17.
Reduced phospho-SLP-76 levels by >50% in peripheral blood and >90% in spleens at 2 hours post-dose on days 8 and 17.
Increased circulating serum IFN-γ, IL-2, and total IgG levels significantly relative to vehicle on day 17.
Increased infiltration of activated B cells (CD19+ MHC-II+) and cytotoxic T cells (CD8+ GrzmB+), as well as numbers of CD8+ T cells, NK cells, B cells, dendritic cells, and M1 macrophages in tumor tissue significantly relative to vehicle.
Achieved complete responses in 6 out of 20 mice; all complete response mice rejected tumor re-challenge, while naive mice developed tumors reaching ~1200 mm3 by day 28.
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Animal Model:BALB/c (female, syngeneic CT-26 and B16F10 tumor model)[2]
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Dosage:75 mg/kg; 150 mg/kg
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Administration:p.o.; once daily; 12, 20 days
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Result:Induced ~40% tumor growth inhibition relative to vehicle at 75 mg/kg, while anti-PD-1 had no effect.
Increased serum levels of IFN-γ, IL-1β, TNF-α, IgG2a, and IgG2b significantly relative to vehicle after 5 days of dosing, while anti-PD-1 had no effect on these analytes.
化学情報
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CAS 番号 2628486-22-4
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分子量 486.54
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分子式 C27H27FN6O2
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SMILES
O=C1NCC2=C(C3=CN=C4N3C=CC(F)=C4)C=CC(NC5=CC=C([C@@]6([H])COCC6)C(CN(C)C)=N5)=C21
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
Calculators
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