MS1129
MS1129 is a DNMT degrader that induces proteasomal degradation of DNMT1, DNMT3A and DNMT3B proteins. MS1129 upregulates TRAIL, DR4 and DR5 proteins, downregulates the decoy receptor DcR2, and activates TRAIL-dependent apoptosis via the HIF-1/2 and Caspase-10 pathways. MS1129 is applicable to the research of VHL-deficient clear cell renal cell carcinoma.
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- Formule: C30H24N4O3
- Masse moléculaire:488.54
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
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Activité biologique
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DNMT1 |
DNMT3A |
DNMT3B |
Caspase-10 |
Caspase-3 |
Caspase-7 |
MS1129 (2 μM; 3 days) induces robust apoptosis in parental VHL-deficient RCC10 clear cell renal cell carcinoma cells, and this effect is dependent on the expression of HIF-1α/2α[1].
MS1129 inhibits the viability of parental VHL-deficient RCC10 clear cell renal cell carcinoma (ccRCC) cells with an IC50 of 1.3 μM, while its potency decreases in HIF-1α/2α double knockout (DKO) RCC10 cells (IC50 = 3.2 μM)[1].
MS1129 (2 μM; 0-48 h) induces time-dependent proteasomal degradation of DNMT1, DNMT3A and DNMT3B proteins in RCC10 clear cell renal cell carcinoma cells, with the maximum degradation level reached at 48 h[1].
MS1129 (1-3 μM; 2 days) induces apoptosis in RCC10 clear cell renal cell carcinoma (ccRCC) cells by activating caspase-3, caspase-7 and PARP1, while the pan-caspase inhibitor Z-VAD-FMK (HY-16658B) partially inhibits this effect[1].
MS1129 (2 μM; 2 days) activates the TRAIL death receptor signaling pathway in RCC10 ccRCC cells by upregulating TRAIL, DR4 and DR5, downregulating DcR2, and inducing caspase-10 cleavage[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Parental VHL-deficient RCC10 ccRCC cells, HIF-1α/2α-DKO RCC10 ccRCC cells
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Concentration:2 μM
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Incubation Time:3 days
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Result:Induced robust cell death in parental RCC10 cells, resulting in ~80% PI-positive cells.
Showed minimal PI-positive cells in HIF-1α/2α-DKO RCC10 cells, comparable to vehicle controls.
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Cell Line:RCC10 ccRCC cells
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Concentration:2 μM (MS1129); 10 μM MG132 (co-treatment); 2 μM MG262 (co-treatment)
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Incubation Time:0, 12, 18, 24, 36, 48 h (MS1129); 6 h (MG132 after 36 h MS1129); 2 h (MG262 after 36 h MS1129)
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Result:Induced time-dependent proteasomal degradation of DNMT1, DNMT3A, and DNMT3B proteins, with degradation detectable as early as 12 h and progressing through 48 h.
Blocked degradation of DNMT proteins when co-treated with proteasome inhibitors MG132 or MG262.
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Cell Line:RCC10 ccRCC cells
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Concentration:1-3 μM (MS1129); 2 μM (MS1129 with Z-VAD-FMK); 20 μM Z-VAD-FMK (pre-treatment)
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Incubation Time:2 days (1-3 μM MS1129); 3 days (2 μM MS1129 with Z-VAD-FMK); 30 min (Z-VAD-FMK pre-treatment)
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Result:Induced dose-dependent increases in cleaved caspase-3, cleaved caspase-7, and cleaved PARP1 levels in RCC10 cells after 2 days of treatment.
Reduced PI-positive cells from ~80% to ~30% when cells were pre-treated with 20 μM Z-VAD-FMK prior to 2 μM MS1129 treatment for 3 days.
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Cell Line:RCC10 ccRCC cells
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Concentration:2 μM
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Incubation Time:2 days
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Result:Upregulated protein levels of TRAIL, DR4, and DR5.
Downregulated protein levels of decoy receptor DcR2.
Induced cleavage of procaspase-10 to active cleaved caspase-10.
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUClast | Vz/F | CL/F | MRT |
|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 5 mg/kg | i.p. | 294 min | 90 min | 618 ng/mL | 178978 min·ng/mL | 11359 mL | 26.8 mL/min | 352 min |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) (male, 6-8 weeks old, subcutaneous implantation of 786-O cells)[1]
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Dosage:5 mg/kg
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Administration:i.p.; daily; 10 days
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Result:Reduced tumor volume relative to vehicle controls.
Lowered tumor weights significantly compared to vehicle-treated mice.
Remained stable in mouse body weight throughout treatment.
Chemical Information
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Masse moléculaire 488.54
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Formule C30H24N4O3
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SMILES
COC1=C(C=CC=C1)C(NC2=CC=C(C=C2)NC(C3=CC=C(C=C3)NC4=CC=NC5=C4C=CC=C5)=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)
MS1129 Related Classifications
HY-181955 Related Classifications
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