JMC14
JMC14 is a selective and orally active PI3Kδ and CSF1R inhibitor with IC50 values of 12 nM and 143 nM, respectively. JMC14 preferentially inhibits PI3Kδ-mediated signaling at the cellular level. JMC14 demonstrates potent antitumor activity against B-cell lymphomas and triple-negative breast cancer (TNBC) in both in vitro and vivo studies. JMC14 can be used for the study of antitumor immunity.
For research use only. We do not sell to patients.
- CAS No.: 2256080-83-6
- Formula: C26H34F3N7O2
- Molecular Weight:533.59
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
PI3Kα 389 nM (IC50) |
PI3Kβ 890 nM (IC50) |
PI3Kγ ＞10000 nM (IC50) |
In Vitro
JMC14 (0-10 μM, 1 h) inhibits DLBCL cell proliferation via blocking PI3K-mediated signaling[1].
JMC14 (0.01-10 μM, 72 h) exerts potent anti-proliferative activity in M-NFS-60 cells by disrupting the CSF1/CSF1R signaling axis and its downstream pathways[1].
JMC14 (0.01-10 μM, 72 h) suppresses the proliferation of triple-negative breast cancer cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:M-NFS-60 myeloid leukemia cells
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Concentration:0.01, 0.1, 1, 10 μM
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Incubation Time:72 h
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Result:Concentration-dependently inhibited the proliferation stimulated by CSF-1. Had inhibitory potency on M-NFS-60 cell proliferation with IC50 values of 289 nM and 221 nM, respectively.
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Cell Line:TNBC 4T1, PY8119 and EMT6
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Concentration:0.1, 1, 10 μM
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Incubation Time:72 h
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Result:Demonstrated moderate antiproliferative activity against all three cell lines, with IC50 values of 7.9 μM, 5.5 μM, or 6.5 μM, respectively.
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Cell Line:ABC-DLBCL TMD8 cells, GCB-DLBCL SU-DHL-6 and Pfeiffer cells
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Concentration:1 μM, 10 μM
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Incubation Time:1 h
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Result:Suppressed AKT phosphorylation at S473 and T308 in a concentration-dependent manner. Reduced AKT phosphorylation levels by approximately 40%. Effectively inhibited the phosphorylation of downstream targets such as p70S6K1, 4E-BP1, and S6 at 1 μM. Reduced AKT phosphorylation at S473 by 44.7%, while phosphorylation of p70S6K1 at T389 and S6 at S240/242 or S235/236 decreased by 39.7%, 55.4% or 50.6%, respectively at 10 μM.
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Cell Line:TMD8, SU-DHL-6, Pfeiffer
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Concentration:0, 0.01, 0.03, 0.1, 0.3, 1.0 μM
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Incubation Time:1 h
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Result:Suppressed AKT phosphorylation at S473 and T308 in a concentration-dependent manner across all analyzed DLBCL cell lines.
Inhibited AKT phosphorylation by approximately 40% at 1 μM or 10 μM in TMD8 and Pfeiffer cells.
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Cell Line:TNBC 4T1, PY8119 and EMT6
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Concentration:0, 0.1, 0.3, 1, 10 μM
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Incubation Time:1 h
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Result:Inhibited the phosphorylation of AKT, S6K, and S6, key signaling components downstream of PI3K, in a concentration-dependent manner.
was required to achieve similar levels to inhibit the phosphorylation of S6K and S6 compared to that of AKT with lower concentration.
Exerted lower potency in inhibiting Erk1/2 phosphorylation, achieving only 20% inhibition at a concentration of 10 μM.
In Vivo
JMC14 (100 mg/kg, p.o., once daily for 13 days) displays potent activity via blocking CSF1R and PI3K signaling in M-NFS-60 myeloid leukemia model[1].
JMC14 (25-100 mg/kg, p.o., once daily for 18 days) attenuates the growth of PY8119 allografts and reprograms the TME[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:TMD8 xenograft model (B-cell lymphoma), female Balb/c SCID mice[1]
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Dosage:10 mg/kg, 30 mg/kg, 100 mg/kg
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Administration:Oral gavage (p.o.), once daily for 21 days
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Result:Resulted in a dose-dependent inhibition of tumor growth.
Significantly inhibited the growth of xenografts with a T/C value of 17.6%.
Reduced significantly phosphorylated AKT at S473 1 h after administration at both 30 and 100 mg/kg.
Recovered phosphorylated AKT 8 h after treatment at 30 mg/kg, while inhibition of AKT phosphorylation persisted up to 8 h and was reversed up to 24 h upon treatment.
Significantly suppressed the growth of LY-24-0063 PDX, resulting in a T/C value of 35.2% at 100 mg/kg.
Exhibited marginal effect, with T/C values of 94.0% or 82.5%, respectively at 10 mg/kg or 30 mg/kg.
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Animal Model:SCID mice bearing M-NFS-60 xenografts model[1]
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Dosage:100 mg/kg
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Administration:Oral gavage (p.o.), once daily for 13 days
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Result:Significantly suppressed tumor growth, yielding a T/C value of 25.4% at 100 mg/kg.
Observed no significant changes in body weight between treatment and control groups.
Decreased the anti-tumor effect correlated with the suppression of CSF1R and PI3K signaling pathways in the phosphorylation of CSF1R, Erk1/2, AKT, S6K and S6 in tumor tissues collected 2 h after a single dose.
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Animal Model:Immune-competent model induced in PY8119 cells established in C57BL/6 mice[1]
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Dosage:25, 50, 100 mg/kg
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Administration:Oral gavage (p.o.)., once daily for 18 days
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Result:Inhibited the tumor growth in a dose-dependent manner.
Exhibited pronounced tumor growth inhibition with a T/C value of 26.9% at 100mg/kg.
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Animal Model:Immune-competent model, PY8119 cells were orthotopically inoculated into C57BL/6 mice[1]
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Dosage:100 mg/kg
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Administration:Oral gavage (p.o.), single dose, tumor tissues were collected at 2, 4, and 8 h after treatment.
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Result:Effectively downregulated the phosphorylation of CSF1R, AKT, S6K, and S6 within 2 h after administration, while a longer time was needed to suppress the Erk1/2 phosphorylation.
Recovered phosphorylation of AKT and S6 partially 8 h post-treatment.
Increased the staining CD45 markedly after treatment, indicating enhanced immune cell infiltration.
Decreased the F4/80 staining, the staining of CD206 representing immunosuppressive M2 macrophages significantly particularly.
Application
1. This compound can be used as a tracer
2. This compound can be used as an internal standard for quantitative analysis by NMR, GC-MS, or LC-MS.
Chemical Information
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CAS No. 2256080-83-6
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Molecular Weight 533.59
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Formula C26H34F3N7O2
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SMILES
OC(C1CCN(CC1)CC2=C(N3N=C(N=C(C3=C2)N4CCOCC4)C5=CN=C(C=C5C(F)(F)F)N)C)(C)C
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Subcutaneous Cell-Line-Derived Xenograft
Subcutaneous cell-line-derived xenograft (CDX) models are established by implanting cultured human cancer cell lines into immunodeficient mice, where the injected cells form localized tumors that can be monitored in vivo as a measure of tumorigenic potential, growth kinetics, and treatment response. These models are widely used in oncology research because they allow reproducible tumor formation and enable comparative assessment of tumor growth between different cell lines or genetic manipulations in a controlled in vivo microenvironment. Subcutaneous implantation of cancer cells in immunodeficient mice is a standard approach for evaluating tumor growth behavior and therapeutic response across multiple cancer types, including prostate, esophageal, pancreatic, and colon cancer models.
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Breast Cancer Modeling
Breast cancer is a heterogeneous cancer, and it has been distinguished into four subtypes: luminal A, luminal B, HER2-positive and basal-like. Molecular mutations, epigenetic alterations, hormone exposure and immune microenvironment are related to the progression of breast cancer.
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Research Protocol for Cancer Immunology
Cancer immunology studies how the immune system recognizes, suppresses, edits, or fails to eliminate malignant cells through tumor antigen release, antigen presentation, T-cell priming, immune trafficking, tumor-cell killing, and feedback inhibition in the tumor microenvironment. The cancer-immunity cycle links tumor antigenicity, dendritic-cell priming, CD8+ T-cell infiltration, cytotoxic function, and immune-checkpoint regulation to tumor rejection or immune escape. Immune-checkpoint pathways such as PD-1/PD-L1 and CTLA-4 suppress antitumor T-cell activity and can be therapeutically blocked, but many tumors remain resistant because of poor antigen presentation, weak T-cell infiltration, suppressive myeloid cells, regulatory T cells, and tumor-intrinsic immune-exclusion programs. Unresolved questions include which immune-cell states predict response, how tumor-intrinsic pathways exclude immune cells, how myeloid suppression limits checkpoint blockade, and which combination strategies
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
JMC14 Related Classifications
HY-174366 Related Classifications
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