2. PROTAC Epigenetics Apoptosis
  3. PROTACs Histone Methyltransferase Apoptosis
  4. PROTAC EZH2 Degrader-9

PROTAC EZH2 Degrader-9 is orally active EZH2 PROTAC degrader degrading EZH2 via the ubiquitin-proteasome pathway. PROTAC EZH2 Degrader-9 downregulates PRC2 core subunits and potent inhibition of H3K27me3 without affecting common CRBN neosubstrates while it was selective over GSp'T1 and ikZF1/3. PROTAC EZH2 Degrader-9 exhibits potent antiproliferative activity against multiple cancer cell lines by inducing cell cycle and apoptosis. PROTAC EZH2 Degrader-9 reverses PRC2-mediated gene silencing and inhibiting EZH2 non-catalytic target gene activation. PROTAC EZH2 Degrader-9 can be used for leukemia, lymphoma, and non-small cell lung cancer research.
(Pink: EZH2 ligand (HY-78694); Blue: Cereblon ligand (HY-W087383); Black: linker).

For research use only. We do not sell to patients.

PROTAC EZH2 Degrader-9

PROTAC EZH2 Degrader-9 Chemical Structure

CAS No. : 2978620-84-5

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PROTAC EZH2 Degrader-9 Related Antibodies

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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 NSD3/WHSC1L1 SETD7/KMT7 SETD8/KMT5A PRMT1 PRMT3 PRMT4 PRMT5 PRMT6 PRMT7 PRMT8

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Description

PROTAC EZH2 Degrader-9 is orally active EZH2 PROTAC degrader degrading EZH2 via the ubiquitin-proteasome pathway. PROTAC EZH2 Degrader-9 downregulates PRC2 core subunits and potent inhibition of H3K27me3 without affecting common CRBN neosubstrates while it was selective over GSp'T1 and ikZF1/3. PROTAC EZH2 Degrader-9 exhibits potent antiproliferative activity against multiple cancer cell lines by inducing cell cycle and apoptosis. PROTAC EZH2 Degrader-9 reverses PRC2-mediated gene silencing and inhibiting EZH2 non-catalytic target gene activation. PROTAC EZH2 Degrader-9 can be used for leukemia, lymphoma, and non-small cell lung cancer research[1]. (Pink: EZH2 ligand (HY-78694); Blue: Cereblon ligand (HY-W087383); Black: linker).

IC50 & Target[1]

EZH2

 

In Vitro

PROTAC EZH2 Degrader-9 (compound 5g) (0-10 μM, 0-48 h) induces the degradation of EZH2 in dependent on the ubiquitin–proteasome system and the binding to the E3 ligase CRBN in MV4–11 cells[1].
PROTAC EZH2 Degrader-9 (72 h) has antiproliferative activity in several cancer, including MV4–11 and MOLM-13 (leukemia), SU-DHL-4 and SU-DHL-6 (large B-cell lymphoma), A549, NCI-H1299, and NCI-H1703 (small cell lung cancer) with IC50s of 2.22, 2.60, 6.35, 9.23, 19.26, 4.41, and 6.35 μM, respectively, exhibits a significant negative correlation with the expression of EZH2 (Pearson r = −0.860, p = 0.013) and CRBN (Pearson r = −0.726, p = 0.049) [1].
PROTAC EZH2 Degrader-9 (10 μM, 24 h) exerts antiproliferative activities by degrading EZH2 and other PRC2 subunits in NCI-H1299, NCI-H1703, MOLM-13, and A549 cells[1].
PROTAC EZH2 Degrader-9 (10 μM, 72 h) induces 1,314 differentially expressed genes with 657 genes up-regulated and 657 genes downregulated, impacts several biological processes, including DNA repair, mitotic cell cycle, and G2/M transition of mitotic cell cycle, enriches differentially expressed genes in cancer-related pathways, particularly those governing the cell cycle, cause negative enrichment in the G2/M checkpoint pathway, and positive enrichment in the apoptosis pathway[1].
PROTAC EZH2 Degrader-9 (0.12-10 μM, 24 h and 72 h) causes cell cycle arrested in the G0/G1 phase, preventing progression into S and G2/M phases and dose-dependently induces apoptosis in MV4–11 cells[1].
PROTAC EZH2 Degrader-9 (1-10 μM, 72 h) alters gene expressions that are regulated by EZH2 catalytic and non-catalytic activities in MV4–11 cells[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

PROTAC EZH2 Degrader-9 Related Antibodies

Western Blot Analysis[1]

Cell Line: MV4–11 cells
Concentration: 0, 0.06, 0.13, 0.25, 0.5, 1.0, 3.0 and 10 μM
Incubation Time: 0, 0.5, 1, 2, 4, 8, 24, 48 h
Result: Decreased PRC2 levels with 10 μM at different durations.
Degraded EZH2, EED, SUZ12, and RbAp46 protein levels with 10 μM for 24 and 48 h.
Inhibited the expression of H3K27me3 at 10 μM 24 h, and achieved an almost complete elimination with 10 μM for 48 h.
Had a minimal impact on EZH2 at low concentrations of ≤ 0.25 μM h with different durations for 24 h.
Induced the degradation of all PRC2 core subunits (EZH2, EED, SUZ12, and RbAp46) at higher concentrations.
Observe no obvious changes in protein levels of GSPT1, IKZF1 or IKZF3 with different concentration for 24 h.
Exhibited no obvious effects on mRNA expression levels of EZH2, EED, SUZ12, and RbAp46 at either 3 or 10 μM.
Induced degradation of EZH2 can be reversed by MLN4924.

Western Blot Analysis[1]

Cell Line: NCI-H1299, NCI-H1703, MOLM-13, and A549 cells
Concentration: 10 μM
Incubation Time: 24 h
Result: Induced the degradation of EZH2 as well as PRC2 subunits SUZ12, EED, and RbAp46 in in NCI-H1299 and NCI-H1703 cells.
Weakly against EZH2 and decreased PRC2 subunits in MOLM-13 cells.
Had no obvious degradation effect on PRC2 subunits in A549 cells.

Cell Cycle Analysis[1]

Cell Line: MV4–11 cells
Concentration: 0.12, 0.37, 1.11, 3.33, 10 μM
Incubation Time: 24 h
Result: Demonstrated a significant dose-dependent rise in cell populations at the G0/G1 phase, increased to 63.20 %, 64.61 %, 66.12 %, 69.89 %, and 73.60 % at different concentration.

Real Time qPCR[1]

Cell Line: MV4-11 cells
Concentration: 1, 3 and 10 μM
Incubation Time: 72 h
Result: Up-regulated the mRNA expressions of PRC2- dependent genes, including ADRB2, CDKN2A, TXINP, and TNFRSF21 in a dose-dependent manner.
Downregulated the expression of several genes known as targets of EZH2 noncanonical functions, including ARL6IP, BRIC5, CENPK, CHEK1, TACC3, TRAP, CDC25A, and E2F1.
Not affected the expression of c-Myc.
Parmacokinetics
Species Dose Route Cmax T1/2 CL AUC0-t Vz MRT0-t F
Mice[1] 1 mg/kg i.v. 3536.71 μg/L 2.32 h 0.13 L/h/kg 7.56 mg·h/L 0.44 L/kg 3.23 h /
Mice[1] 10 mg/kg p.o. 989 μg/L 2.43 h 1.50 L/h/kg 6732.54 μg/L·h 5.26 L/kg 4.91 h 8.91 %
Molecular Weight

882.06

Formula

C51H59N7O7
CAS No.
SMILES

O=C1CCC(C(N1)=O)N2C(C3=C(C2=O)C=C(N4CC5(CCN(CC6=CC=CC(C7=CC(C(NCC8=C(C=C(NC8=O)C)C)=O)=C(C)C(N(C9CCOCC9)CC)=C7)=C6)CC5)CC4)C=C3)=O
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Purity & Documentation
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PROTAC EZH2 Degrader-9 Related Classifications

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Keywords:

PROTAC EZH2 Degrader-92978620-84-5PROTACsHistone MethyltransferaseApoptosisEZH2PROTACubiquitin-proteasomeCRBNapoptosisleukemialymphomaand non-small cell lung cancerInhibitorinhibitorinhibit

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