G9D-4
G9D-4 is a G9a PROTAC degrader. G9D-4 induces G9a degradation, reduces H3K9me2 levels, and prevents GLP interference via the CRBN ternary complex, proteasome and ubiquitin-like modification-dependent pathways. G9D-4 exerts antiproliferative activity and induces Apoptosis in pancreatic cancer cells. G9D-4 can be used for research on pancreatic cancer.
(Pink: EHMT2/G9a/KMT1C ligand (HY-15273); Blue: Cereblon ligand (HY-10984); Black: linker).
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- CAS No.: 3097803-96-5
- Formule: C53H75N9O7
- Masse moléculaire:950.22
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Activité biologique
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Activité biologique
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Cereblon |
G9D-4 (0.008-20 μM; 0-24 h) induces G9a degradation in PANC-1 and ASPC-1 cells, with DC50 values of 0.1 μM and 0.2 μM, respectively. It accelerates the degradation of G9a protein in PANC-1 cells without altering GLP protein levels[1].
G9D-4 (0.04-10 μM; 24 h) reduces the level of H3K9me2 in PANC-1 cells[1].
G9D-4 (1 μM; 8 h) induces G9a degradation in PANC-1 cells. This process requires the formation of a G9a-G9D-4-CRBN ternary complex and is dependent on the neddylation-proteasome pathway[1].
G9D-4 (72 h) inhibits the cell growth of a panel of pancreatic cancer cell lines (KP-4, PANC-1, ASPC-1,
HPAF-II, Panc10.05, SW1990, Panc08.13, Panc04.03, Panc05.04, and Panc02.03 cells), with IC50 values ranging from 12 to 32 μM. It also inhibits the growth of 22Rv1 cells, with an IC50 of 9.9 μM[1].
G9D-4 (0.1-12.5 μM; 24 h) induces apoptosis in PANC-1 cells, downregulates G9a and H3K9me2, and upregulates γH2AX and cleaved PARP[1].
G9D-4 (0-15 μM; 72 h) enhances the inhibitory effect of MRTX1133 (HY-134813) on cell proliferation of KRASG12D-mutant pancreatic cancer cell lines (ASPC-1 cells and KP-4 cells), and synergistically induces cell apoptosis[1].
G9D-4 (5-10 μM; 10−14 days) significantly enhances the colony formation inhibitory activity of MRTX1133 in KP-4 cells, and exerts a synergistic inhibitory effect on long-term cell proliferation[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:PANC-1 cells
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Concentration:0.008, 0.04, 0.2, 1, 5, 10 μM (dose-response); 1 μM (time-course)
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Incubation Time:8 h (dose-response); 0, 2, 4, 6, 8, 16, 24 h (time-course)
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Result:Induced dose-dependent G9a degradation with a DC50 of 0.1 μM. Did not alter GLP protein levels.
Triggered G9a degradation starting after 8 h and continuing through 24 h.
Selectively and dose-dependently reduced H3K9me2 levels.
Induced significant G9a degradation as early as 4 h.
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Cell Line:PANC-1 cells
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Concentration:5-12.5 μM (24 h); 10 μM (time-course)
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Incubation Time:24 h (dose-response); 12, 24, 48, 72 h (time-course)
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Result:Induced significant apoptosis in a dose-dependent manner at 24 h, with ~70% of cells apoptotic at 12.5 μM.
Caused time-dependent apoptosis at 10 μM, with ~60% of cells apoptotic at 72 h.
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Cell Line:ASPC-1 cells
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Concentration:0.008, 0.04, 0.2, 1, 5, 10, 15, 20 μM
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Incubation Time:8 h
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Result:Induced dose-dependent G9a degradation with a DC50 of 0.2 μM.
Did not alter GLP protein levels.
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Cell Line:PANC-1 cells
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Concentration:0.1, 1, 10 μM
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Incubation Time:24 h
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Result:Dose-dependently reduced G9a and H3K9me2 levels.
Dose-dependently increased γH2AX and cleaved PARP levels, indicating induction of DNA damage and apoptosis.
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Cell Line:ASPC-1, KP-4, Panc02.03, Panc10.05, HPAFII, Panc08.13 KRASG12D mutant pancreatic cancer cell lines
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Concentration:30 μM starting concentration, 1.2-fold serial dilutions (ASPC-1); 20 μM starting concentration, 1.2-fold serial dilutions (KP-4); fixed concentrations (co-treated with MRTX1133)
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Incubation Time:72 h
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Result:Combined with MRTX1133 showed strong synergistic antiproliferative activity. Had all CI values below 0.8 (ED50, ED75, ED90), with ED90 CI values below 0.4 across all tested cell lines.
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Cell Line:KP-4, ASPC-1 cells
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Concentration:5-10 μM (alone); 5-10 μM (co-treated with 1-5 μM MRTX1133, respectively)
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Incubation Time:10-14 days
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Result:Alone reduced colony formation. Combined with MRTX1133 almost completely eliminated colony formation, with a significantly greater effect than either single agent.
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Cell Line:ASPC-1, KP-4 cells
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Concentration:10 μM (co-treated with 1 μM MRTX1133, ASPC-1); 10 μM (co-treated with 5 μM MRTX1133, KP-4)
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Incubation Time:24 h
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Result:Combined with MRTX1133 induced significantly higher levels of apoptosis than either single agent.
Triggered ~75% apoptosis in ASPC-1 cells. Triggered ~30% apoptosis in KP-4 cells.
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Cell Line:ASPC-1 cells
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Concentration:10 μM (co-treated with 1 μM MRTX1133)
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Incubation Time:24 h
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Result:Combined with MRTX1133 further reduced H3K9me2 levels and significantly increased γH2AX and cleaved PARP levels compared to either single agent.
Chemical Information
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CAS No. 3097803-96-5
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Masse moléculaire 950.22
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Formule C53H75N9O7
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SMILES
COC1=CC2=C(C=C1OCCCN3CCCC3)N=C(C4CCCCC4)N=C2NC5CCN(CC5)CCCC(NCCCCCCCCCNC6=C(C7=CC=C6)C(N(C7=O)C8C(NC(CC8)=O)=O)=O)=O
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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)
G9D-4 Related Classifications
HY-162749 Related Classifications
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