C199
C199 is a PROTAC degrader targeting PRMT4 (DC50 = 106 nM). C199 shows high selectivity for PRMT4 over other protein arginile methyltransferases. C199 exhibits strong cell degradation ability. C199 induces apoptosis in MM cell lines. C199 efficiently clears PRMT4 protein via the VHL-proteasome pathway. C199 has a relatively long half-life and shows strong anti-multiple myeloma (MM) tumor activity.
(Pink: PRMT4 ligand (HY-111109); Blue: VHL ligand (HY-112078); Black: linker).
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- CAS No.: 3107801-96-4
- Formule: C67H95ClN10O8S
- Masse moléculaire:1236.05
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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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Activité biologique
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VHL |
PRMT4 |
C199 (Compound C199) (0.001-1 μM, 12 days) potently inhibits myeloma cell proliferation[1].
C199 (0.007-0.5 μM, 6 days) induces dose-dependent apoptosis in NCI-H929 cells[1].
C199 (0.01-0.5 μM, 12-72 h) efficiently and selectively degrades PRMT4 protein in NCI-H929 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:NCI-H929 cells
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Concentration:0.007 μM, 0.031 μM, 0.062 μM, 0.125 μM, 0.5 μM
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Incubation Time:6 days
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Result:Apoptosis rates prominently reached 81.9% at 0.5 μM.
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Cell Line:NCI-H929 cells
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Concentration:0.01 μM, 0.03 μM, 0.06 μM, 0.1 μM, 0.12 μM, 0.25 μM, 0.5 μM
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Incubation Time:12 h, 24 h, 48 h, 72 h
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Result:Reached a degradation efficiency of 92 % when the compound concentration was 0.5 μM.
Still maintained a high degradation efficiency of 56 % when the concentration dropped to 0.1 μM.
Had a DC50 of 0.106 μM, caused a significant decrease in PRMT4 level by about half after 24 hours, and reached a Dmax of 93.1 % after 72 hours.
Degraded PRMT4 via a VHL- and proteasome-dependent instead of lysosomal pathway.
Inhibited PABP1 methylation by 97 %, while EZM2302 only inhibited 37 %. Was about three times more efficient than EZM2302 in inhibiting BAF155 methylation.
Affected only the expression of PRMT4 and had no effect on other homologous proteins.
Effectively modulated asymmetric dimethylation of PRMT4 substrates through targeted degradation of the methyltransferase.
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Cell Line:NCI-H929 cells, RPMI-8226 cells
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Concentration:0.001 μM, 0.01 μM. 0.1 μM, 1 μM
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Incubation Time:12 days
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Result:Outperformed the inhibitor EZM2302 significantly (GI50: 0.089 μM for NCI-H929 cells, 0.145 μM for RPMI-8226 cells).
| Species | Dose | Route | Tmax | Cmax | AUClast |
|---|---|---|---|---|---|
| Mice | 10 mg/kg | p.o. | 0.08 h | 255.33 ng/mL | 3843.67 ng·h/mL |
| Mice | 2 mg/kg | i.v. | 0.08 h | 661.33 ng/mL | 7812.14 ng·h/mL |
C199 (Compound C199) (40-80 mg/kg, i.p, twice daily for 20 days) inhibits the growth of multiple myeloma xenografts and downregulated the expression of PRMT4 in BALB/c nude mice without obvious organ toxicity[1].
C199 (100-1000 mg/kg, i.p, once daily for 14 days) has good safety at high doses in CD1 mice, a wide therapeutic window, and excellent safety[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NCI-H929 xenograft model established in female BALB/c nude mice (6-8 weeks, 18-22 g)[1]
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Dosage:40 mg/kg, 80 mg/kg
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Administration:Intraperitoneal injection (i.p.), twice daily for 20 days
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Result:Inhibited tumor growth (TGI = 78 %).
Significantly reduced tumor PRMT4 protein.
Left the heart, liver, spleen and kidneys morphologically normal.
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Animal Model:Famale and male CD1 nude mice[1]
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Dosage:100 mg/kg, 500 mg/kg, 1000 mg/kg
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Administration:Intraperitoneal injection (i.p.), once daily for 14 days
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Result:Left body weight and organ indexes normal, and caused no death or organ damage at 1000 mg/kg.
Chemical Information
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CAS No. 3107801-96-4
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Masse moléculaire 1236.05
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Formule C67H95ClN10O8S
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SMILES
O=C(N[C@H](C1=CC=C(C=C1)C2=C(N=CS2)C)C)[C@H]3N(C[C@@H](C3)O)C([C@H](C(C)(C)C)NC(CCCCCCCCCCCCCCCC(N4CCC5(CN(C5)C6=NC(C7=CC(OC[C@@H](CNC)O)=CC=C7Cl)=NC(C8=C(ON=C8C)C)=C6C)CC4)=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)
C199 Related Classifications
HY-174445 Related Classifications
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