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.
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- CAS No.: 2256080-83-6
- Formule: C26H34F3N7O2
- Masse moléculaire:533.59
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
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Activité biologique
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PI3Kα 389 nM (IC50) |
PI3Kβ 890 nM (IC50) |
PI3Kγ ＞10000 nM (IC50) |
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.
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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.
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.
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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Masse moléculaire 533.59
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Formule 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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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
JMC14 Related Classifications
HY-174366 Related Classifications
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