2. PROTAC Epigenetics Apoptosis
  3. PROTACs Histone Methyltransferase Apoptosis
  4. 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: Target protein ligand (HY-111109); Blue: E3 ligase ligand (HY-112078), E3 ligase ligand + linker (HY-174474); black: Linker).

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C199 Chemical Structure

C199 Chemical Structure

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C199 Related Antibodies

Top Publications Citing Use of Products

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von Hippel-Lindau (VHL) Cereblon MDM2 cIAP1

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EZH1 EZH2 DOT1L SMYD2 SMYD3 SUV39H2/KMT1B EHMT2/G9a/KMT1C EHMT1/GLP/KMT1D ASH1L/KMT2H SETDB1/KMT2G SETD2/KMT3A NSD2/MMSET/WHSC1 SETD7/KMT7 SETD8/KMT5A PRMT1 PRMT3 PRMT4 PRMT5 PRMT6 PRMT7 PRMT8

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Description

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: Target protein ligand (HY-111109); Blue: E3 ligase ligand (HY-112078), E3 ligase ligand + linker (HY-174474); black: Linker)[1].

IC50 & Target

VHL

 

PRMT4

 

In Vitro

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.

C199 Related Antibodies

Apoptosis Analysis[1]

Cell Line: NCI-H929 cells
Concentration: 0.007 μM, 0.031 μM, 0.062 μM, 0.125 μM, 0.5 μM
Incubation Time: 6 days
Result: Apoptosis rates prominently reached 81.9% at 0.5 μM.

Western Blot Analysis[1]

Cell Line: NCI-H929 cells
Concentration: 0.01 μM, 0.03 μM, 0.06 μM, 0.1 μM, 0.12 μM, 0.25 μM, 0.5 μM
Incubation Time: 12 h, 24 h, 48 h, 72 h
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.

Cell Proliferation Assay[1]

Cell Line: NCI-H929 cells, RPMI-8226 cells
Concentration: 0.001 μM, 0.01 μM. 0.1 μM, 1 μM
Incubation Time: 12 days
Result: Outperformed the inhibitor EZM2302 significantly (GI50: 0.089 μM for NCI-H929 cells, 0.145 μM for RPMI-8226 cells).
In Vivo

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.

Animal Model: NCI-H929 xenograft model established in female BALB/c nude mice (6-8 weeks, 18-22 g)[1]
Dosage: 40 mg/kg, 80 mg/kg
Administration: Intraperitoneal injection (i.p.), twice daily for 20 days
Result: Inhibited tumor growth (TGI = 78 %).
Significantly reduced tumor PRMT4 protein.
Left the heart, liver, spleen and kidneys morphologically normal.
Animal Model: Famale and male CD1 nude mice[1]
Dosage: 100 mg/kg, 500 mg/kg, 1000 mg/kg
Administration: Intraperitoneal injection (i.p.), once daily for 14 days
Result: Left body weight and organ indexes normal, and caused no death or organ damage at 1000 mg/kg.
Molecular Weight

1236.05

Formula

C67H95ClN10O8S
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
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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C199 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

C199C 199C-199PROTACsHistone MethyltransferaseApoptosisNCI-H929 cellsRPMI-8226 cellsPRMT4BALB/c miceCD1 miceMultiple MyelomadegradationInhibitorinhibitorinhibit

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