Art. -Nr.: HY-156292

IHMT-EZH2-426

IHMT-EZH2-426 is an orally active and selective EZH2 degrader. IHMT-EZH2-426 forms a covalent bond with Cys663 of EZH2, inhibits its catalytic activity, and reduces the protein levels of EZH2 as well as the level of H3K27me3. IHMT-EZH2-426 acts as an antiproliferative agent against B-cell lymphoma and triple-negative breast cancer cells, and also exhibits anti-tumor related activity in Pfeiffer and MDA‑MB‑231 xenograft models. IHMT-EZH2-426 can be used in studies related to B-cell lymphoma and triple-negative breast cancer.

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CAS. Nr.: 3018914-66-1
Formel: C₃₁H₃₅FN₄O₄S
Molecular Weight:578.70

Speicherung:

Please store the product under the recommended conditions in the Certificate of Analysis.

Data Sheet (295 KB)

IHMT-EZH2-426 Chemical Structure

CAS. Nr.: 3018914-66-1

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Preis

Verfügbarkeit

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Use of MCE Products

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Reinheit & Dokumentation
Verweise
Calculators
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

IC₅₀ & Target

^[1]

EZH2 WT

1.3 nM (IC₅₀)

Alle Histone Methyltransferase Isoform-spezifische Produkte anzeigen :

Cellular Effect

Cell Line	Type	Value	Description	References
Pfeiffer	GI50	0.02 μM	Antiproliferative activity against EZH2-mutant (A677G) human Pfeiffer B-cell lymphoma cells assessed as reduction in cell viability incubated for 5 days by CellTiter-Glo assay. Antiproliferative activity against EZH2-mutant (A677G) human Pfeiffer B-cell lymphoma cells assessed as reduction in cell viability incubated for 5 days by CellTiter-Glo assay.	37826933
KARPAS-422	GI50	0.085 μM	Antiproliferative activity against EZH2-mutant (Y641N) human Karpas-422 B-cell lymphoma cells assessed as reduction in cell viability incubated for 5 days by CellTiter-Glo assay. Antiproliferative activity against EZH2-mutant (Y641N) human Karpas-422 B-cell lymphoma cells assessed as reduction in cell viability incubated for 5 days by CellTiter-Glo assay.	37826933
SU-DHL-4	GI50	1.42 μM	Antiproliferative activity against EZH2-mutant (Y641S) human SU-DHL-4 B-cell lymphoma cells assessed as reduction in cell viability incubated for 5 days by CellTiter-Glo assay. Antiproliferative activity against EZH2-mutant (Y641S) human SU-DHL-4 B-cell lymphoma cells assessed as reduction in cell viability incubated for 5 days by CellTiter-Glo assay.	37826933
SU-DHL-6	GI50	1.95 μM	Antiproliferative activity against EZH2-mutant (Y641N) human SU-DHL-6 B-cell lymphoma cells assessed as reduction in cell viability incubated for 5 days by CellTiter-Glo assay. Antiproliferative activity against EZH2-mutant (Y641N) human SU-DHL-6 B-cell lymphoma cells assessed as reduction in cell viability incubated for 5 days by CellTiter-Glo assay.	37826933
WSUDLCL2	GI50	3.85 μM	Antiproliferative activity against EZH2-mutant (Y641F) human WSU-DLCL2 B-cell lymphoma cells assessed as reduction in cell viability incubated for 5 days by CellTiter-Glo assay. Antiproliferative activity against EZH2-mutant (Y641F) human WSU-DLCL2 B-cell lymphoma cells assessed as reduction in cell viability incubated for 5 days by CellTiter-Glo assay.	37826933
Daudi	GI50	7.01 μM	Antiproliferative activity against EZH2 WT human Daudi B-cell lymphoma cells assessed as reduction in cell viability incubated for 5 days by CellTiter-Glo assay. Antiproliferative activity against EZH2 WT human Daudi B-cell lymphoma cells assessed as reduction in cell viability incubated for 5 days by CellTiter-Glo assay.	37826933
MDA-MB-231	GI50	6.78 μM	Antiproliferative activity against human MDA-MB-231 TNBC cells assessed as reduction in cell viability incubated for 5 days by CellTiter-Glo assay. Antiproliferative activity against human MDA-MB-231 TNBC cells assessed as reduction in cell viability incubated for 5 days by CellTiter-Glo assay.	37826933
MDA-MB-468	GI50	1.93 μM	Antiproliferative activity against human MDA-MB-468 TNBC cells assessed as reduction in cell viability incubated for 5 days by CellTiter-Glo assay. Antiproliferative activity against human MDA-MB-468 TNBC cells assessed as reduction in cell viability incubated for 5 days by CellTiter-Glo assay.	37826933

In Vitro

IHMT-EZH2-426 (compound 38) potently inhibits EZH2 WT and various EZH2^Y641 mutants, with IC₅₀ values ranging from 1.3 nM to 11 nM; in the AlphaLISA enzyme inhibition assay, it shows 113-fold higher selectivity for EZH2 WT than for EZH1 WT^[1].
IHMT-EZH2-426 (0.03-10 μM; 72 h) inhibits H3K27 trimethylation at a concentration of 0.03 μM and reduces EZH2 protein levels at 1 μM after 72 h of treatment in Karpas-422, Pfeiffer, MDA-MB-231 and MDA-MB-468 cell lines^[1].
IHMT-EZH2-426 (10 μg/mL; 72 h treatment, up to 48 h washout) achieves sustained inhibition of H3K27me3 for at least 48 h after washout in MDA-MB-231 cells, confirming its persistent binding to the target^[1].
IHMT-EZH2-426 (1-50 μM; 4 h compound treatment, 4 h probe incubation) binds to EZH2 in MDA-MB-231 cell lysates, and labels approximately 50% of available target proteins at a concentration of 1 μM^[1].
IHMT-EZH2-426 forms a covalent adduct with purified EZH2 (SET domain) protein, confirming its covalent binding mechanism^[1].
IHMT-EZH2-426 (0.1-10 μM; 5 days) potently inhibits the proliferation of EZH2-mutant B-cell lymphoma cell lines (GI₅₀ 0.02-3.85 μM), and exhibits moderate antiproliferative activity against EZH2-wild-type B-cell lymphoma cell lines as well as triple-negative breast cancer (TNBC) cells (GI₅₀ 1.93-7.01 μM)^[1].
IHMT-EZH2-426 (for 14 days) inhibits colony formation of MDA-MB-231 and MDA-MB-468 triple-negative breast cancer (TNBC) cells in a dose-dependent manner^[1].

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

Western Blot Analysis^[1]

Cell Line:

B-cell lymphoma cell lines (Karpas-422, Pfeiffer), TNBC cell lines (MDA-MB-231, MDA-MB-468)
Concentration:

0.03, 0.1, 0.3, 1, 3, 10 μM
Incubation Time:

72 h
Result:

Potently inhibited H3K27 trimethylation at 0.03 μM in Karpas-422, Pfeiffer, MDA-MB-231, and MDA-MB-468 cell lines.
Reduced EZH2 protein levels at 1 μM in Karpas-422, Pfeiffer, MDA-MB-231, and MDA-MB-468 cell lines.

Western Blot Analysis^[1]

Cell Line:

MDA-MB-231 TNBC cells
Concentration:

10 μg/mL
Incubation Time:

72 h (treatment)
0, 2, 4, 6, 8, 12, 24, 48 h (washout)
Result:

Sustained inhibition of H3K27me3 for up to 48 h after washout.

Cell Viability Assay^[1]

Cell Line:

Pfeiffer, Karpas‑422, SU‑DHL‑4, SU‑DHL‑6, WSU‑DHL2, Daudi, Farage, Raji
Concentration:

0.1, 0.3, 1, 3, 10 μM
Incubation Time:

5 days
Result:

Inhibited proliferation of EZH2-mutant B-cell lymphoma cell lines (GI₅₀ 0.02-3.85 μM)
Exhibited moderate antiproliferative activity against EZH2 WT B-cell lymphoma cell lines and TNBC cells, including 3D patient-derived TNBC cells (GI₅₀ 1.93-7.01 μM).

Parmacokinetics

Species	Dose	Route	T_1/2	T_max	C_max	AUC_0-t	V_z	CL	F
Rat^[1]	1 mg/kg	i.v.	1.1 h	0.03 h	1080 ng/mL	296.3 ng·h/mL	5106 mL/kg	3417 mL/h/kg	/
Rat^[1]	10 mg/kg	p.o.	4.08 h	0.14 h	219.7 ng/mL	616.6 ng·h/mL	121510 mL/kg	19069 mL/h/kg	21 %

In Vivo

IHMT-EZH2-426 (compound 38) (100 mg/kg; p.o.; daily; 14 days) exhibits potent in vivo anti-tumor activity against MDA-MB-231 triple-negative breast cancer (TNBC) xenografts, inhibits tumor growth, and simultaneously downregulates the level of H3K27 trimethylation and the expression of EZH2 in tumor tissues^[1].
IHMT-EZH2-426 (100 mg/kg; p.o.; daily; 20 days) exhibits potent in vivo anti-tumor activity against Pfeiffer diffuse large B-cell lymphoma (DLBCL) xenografts^[1].

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

Animal Model:

BALB/c nude mice (female, 5-week old, 5 × 10⁶ MDA-MB-231 cells)^[1]
Dosage:

100 mg/kg
Administration:

p.o.; daily; 14 days
Result:

Suppressed H3K27 trimethylation in tumor tissues.
Reduced EZH2 levels in tumor tissues.
Showed no apparent body weight loss during treatment.

Animal Model:

NCG mice (female, 5-week old, 1 × 10⁷ Pfeiffer cells)^[1]
Dosage:

100 mg/kg
Administration:

p.o.; daily; 20 days
Result:

Demonstrated potent antitumor activity with efficacy comparable to the reference compound.
Showed no apparent body weight loss during treatment.

Chemical Information

CAS. Nr. 3018914-66-1
Molecular Weight 578.70
Formel C₃₁H₃₅FN₄O₄S
SMILES

O=C(C1=CC(C(C=CC(F)=C2)=C2NC(C=C)=O)=CC(N(C3CCOCC3)C)=C1C)NCC4=C(SC)C=C(C)NC4=O
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

Please store the product under the recommended conditions in the Certificate of Analysis.

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (295 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Zhou B, et al. Discovery of dihydropyridinone derivative as a covalent EZH2 degrader. European journal of medicinal chemistry. 2023 Dec 05;261:115825. [Content Brief]

Calculators

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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IHMT-EZH2-426

Alle Histone Methyltransferase Isoform-spezifische Produkte anzeigen