PJ-68
PJ-68 is a selective PRMT5 inhibitor (IC50 = 517 nM). PJ-68 reduces KLF5 methylation, stability, and downstream target gene expression. PJ-68 induces Apoptosis, inhibits self-renewal capacity, blocks the Wnt/β-catenin signaling pathway by reducing DVL3 expression, and decreases BCR-ABL mRNA and protein levels. PJ-68 serves as a Ligand for Target Protein for PROTAC for the synthesis of PRMT5 PROTAC degraders, such as YZ-17 (HY-189213). PJ-68 inhibits the growth of basal-like breast cancer. PJ-68 prolongs the survival of CML mice. PJ-68 is used for research on basal-like breast cancer and chronic myeloid leukemia.
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- No. CAS: 352544-59-3
- Fòrmula: C25H26N2
- Peso molecular:354.49
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Actividad biológica
Descripciòn
IC50 & Target
[1]|
PRMT5 517 nM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HCC1806 | IC50 |
5.3 μM
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Antiproliferative activity against human HCC1806 cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay.
Antiproliferative activity against human HCC1806 cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay.
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42566881 |
| HCC1937 | IC50 |
4.6 μM
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Antiproliferative activity against human HCC1937 cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay.
Antiproliferative activity against human HCC1937 cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay.
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42566881 |
In Vitro
PJ-68 (1-5 μM; 48 h) shows moderate antiproliferative activity against HCC1806 cells[1].
PJ-68 (10-50 μM) specifically inhibits PRMT5 methyltransferase activity and reduces BCR-ABL protein levels in K562 cells[2].
PJ-68 inhibits BCR-ABL gene transcription in K562 cells[2].
PJ-68 inhibits the transcription of the DVL3 gene in K562 cells[2].
PJ-68 reduces the enrichment of PRMT5 at the p15INK4B promoter in K562 cells[2].
PJ-68 (25.0 μM; 1 week) inhibits LTC-IC capacity in CML BM cells, and its combination with IM enhances this effect[2].
PJ-68 reduces H3R2SDM levels in K562 and CML CD34+ cells[2].
PJ-68 increases p15INK4B mRNA levels in K562 and CML CD34+ cells[2].
PJ-68 (0-6.0 μM; 24 h) does not significantly inhibit PRMT5-mediated sDMA modification in HCC1806 cells at concentrations up to 6 μM[1].
PJ-68 is a potent and selective inhibitor of PRMT5 methyltransferase activity with an IC50 of 517 nM[2].
PJ-68 inhibits PRMT5-mediated KLF5 methylation in cell-free in vitro methylation assays[3].
PJ-68 (5 μM; 6 h) decreases KLF5-WT protein levels in HEK293T cells, but does not decrease KLF5-R57K protein levels[3].
PJ-68 reduces the recruitment of PRMT5 and its epigenetic marks to the Mir203 promoter in K562 cells[2].
PJ-68 (25.0 μM; 96 h) selectively induces apoptosis in quiescent CML LSCs compared with NBM CD34+ cells[2].
PJ-68 increases the expression of cell cycle inhibitors p15INK4B and p27KIP1 in CML CD34+ cells[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HCC1806
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Concentration:1 μM; 5 μM
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Incubation Time:48 h
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Result:Inhibited cell viability by 10.6% at 1 μM.
Inhibited cell viability by 40.7% at 5 μM.
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Cell Line:HCC1806
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Concentration:0; 0.5; 1.0; 2.0; 4.0; 6.0 μM
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Incubation Time:24 h
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Result:Did not significantly reduce sDMA levels at 6 μM.
In Vivo
PJ-68 (20-40 mg/kg; i.p.; daily; 3 weeks) significantly inhibits breast tumor growth in vivo in a dose-dependent manner by decreasing KLF5 and its downstream target proteins[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (6- to 8-week-old male donors and female recipients; retroviral BCR-ABL-driven CML model)[2]
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Dosage:25 mg/kg/d and 50 mg/kg/d
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Administration:i.p.; for 2 weeks
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Result:Significantly prolonged survival of CML mice.
Extended survival further when combined with IM compared with each agent alone.
Did not observe splenomegaly in treated mice.
Significantly reduced the proportion of BCR-ABL-expressing (GFP+) leukemia cells and myeloid cells (Gr-1+ Mac-1+) in BM.
Markedly decreased the proportion of LSK cells, LT-HSCs, and ST-HSCs, as well as GMP and CMP in BM cells.
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Animal Model:C57BL/6 (WT recipient mice; limiting dilution secondary transplantation of CML BM cells)[2]
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Dosage:25 mg/kg/d and 50 mg/kg/d
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Administration:i.p.; for 2 weeks (administered to primary CML mice prior to BM harvest)
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Result:Greatly decreased the engraftment of GFP+ cells and the frequency of CML stem cells in secondary recipients.
Showed LT-HSC frequency of 1/1,437,773 for treated mice versus 1/223,325 for control and 1/426,051 for IM.
Decreased LT-HSC frequency to 1/3,283,885 when combined with IM.
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Animal Model:Nude mice (female, 7 weeks old, HCC1806 cell-derived xenografts in mammary fat pads)[3]
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Dosage:20-40 mg/kg
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Administration:i.p.; daily; 3 weeks
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Result:Inhibited tumor growth in a dose-dependent manner.
Decreased tumor weights following sacrifice.
Did not cause statistical differences in body weight among dose groups.
Decreased protein levels of KLF5 and its targets in primary tumor samples in a dose-dependent manner.
Chemical Information
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No. CAS 352544-59-3
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Peso molecular 354.49
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Fòrmula C25H26N2
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SMILES
CCN1C2=C(C3=C1C=CC=C3)C=C(CNC4CCCC5=C4C=CC=C5)C=C2
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PJ-68 Related Classifications
HY-124784 Related Classifications
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