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Chemical Structure| 1598383-40-4 Chemical Structure| 1598383-40-4

Structure of EPZ011989
CAS No.: 1598383-40-4

Chemical Structure| 1598383-40-4

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EPZ011989 is a potent, selective orally bioavailable EZH2 inhibitor with Ki < 3 nM for EZH2 wt and EZH2 Y646 with 15-fold selectivity over EZH1 and > 3000-fold selectivity over other HMTase.

Synonyms: EPZ011989

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Product Details of EPZ011989

CAS No. :1598383-40-4
Formula : C35H51N5O4
M.W : 605.81
SMILES Code : O=C(NCC1=C(C)C=C(C)NC1=O)C2=CC(C#CCN3CCOCC3)=CC(N(CC)[C@H]4CC[C@H](N(CCOC)C)CC4)=C2C
Synonyms :
EPZ011989
MDL No. :MFCD28964159
InChI Key :XQFINGFCBFHOPE-UHFFFAOYSA-N
Pubchem ID :73670548

Safety of EPZ011989

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Related Pathways of EPZ011989

epigenetics

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Primary AML cells 1 µM 7 days EPZ reduced H3K27me3 levels in primary AML samples Cancers (Basel). 2024 Jan 29;16(3):569
NCI-H446 1 µM 1 hour To assess the effect of EPZ011989 on EZH2 activity and H3K27me3 levels under DNA damage conditions. Results showed that EPZ011989 suppressed the DNA damage-induced increase in EZH2 activity and H3K27me3 levels. Cancer Cell. 2017 Feb 13;31(2):286-299
NCI-H82 1 µM 10 days To evaluate the effect of EPZ011989 on restoring SLFN11 expression and sensitivity to DNA damaging agents. Results showed that EPZ011989 treatment significantly restored SLFN11 expression and enhanced sensitivity to topotecan. Cancer Cell. 2017 Feb 13;31(2):286-299
Normal CD34+ stem cells 1 µM 7-10 days EPZ had no effect on colony formation in normal CD34+ stem cells Cancers (Basel). 2024 Jan 29;16(3):569
MV4-11 cells 0.5 µM or 1 µM 96 hours EPZ decreased H3K27me3 in all three AML cell lines Cancers (Basel). 2024 Jan 29;16(3):569
OCI-AML3 cells 0.5 µM or 1 µM 96 hours EPZ decreased H3K27me3 in all three AML cell lines Cancers (Basel). 2024 Jan 29;16(3):569
MOLM-13 cells 0.5 µM or 1 µM 96 hours EPZ decreased H3K27me3 in all three AML cell lines Cancers (Basel). 2024 Jan 29;16(3):569
ES-1 cells 10 and 100 μM 96 hours To evaluate the effect of EPZ-011989 on cell growth, results showed that EPZ-011989 significantly inhibited H3K27me3 levels and increased H3K27ac levels, while inducing the accumulation of the autophagy marker LC3B-II. Cancers (Basel). 2019 Jul 19;11(7):1015
neural progenitor cells 1 µM 5 days To evaluate the effect of EZH2 inhibition on cell proliferation, results showed that EZH2 inhibition accelerated cell proliferation. Acta Neuropathol Commun. 2022 Apr 8;10(1):47.
MKL-1 3 μM 6 and 12 days To assess the transcriptional changes in MKL-1 cells treated with EPZ011989, observing upregulation of SIX1 and increased expression of its downstream gene MYO6 J Invest Dermatol. 2022 Oct;142(10):2783-2792.e15.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice Patient-derived xenograft (PDX) models of SCLC Oral 250 mg/kg Twice daily for 21 days To evaluate the effect of EPZ011989 in combination with standard chemotherapeutic agents on tumor growth control. Results showed that EPZ011989 combined with chemotherapy significantly enhanced disease control and prevented the emergence of chemoresistance. Cancer Cell. 2017 Feb 13;31(2):286-299
NCG mice MOLM-13 luciferase xenograft model Oral gavage 82 mg/kg increased to 300 mg/kg Daily administration until study endpoint EPZ-treated mice had slower leukemia development and a modest improvement in overall survival (20.5 vs. 23 days, p=0.02) Cancers (Basel). 2024 Jan 29;16(3):569
SCID mice INI1-deficient proximal-type epithelioid sarcoma patient-derived xenograft model (PDX ES-1) Oral 500 mg/kg Twice daily for 28 days To assess the antitumor activity of EPZ-011989 in vivo, results showed that EPZ-011989 significantly inhibited tumor growth (max tumor volume inhibition of 89%) and induced autophagy as a possible survival mechanism in residual tumor cells. Cancers (Basel). 2019 Jul 19;11(7):1015

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.65mL

0.33mL

0.17mL

8.25mL

1.65mL

0.83mL

16.51mL

3.30mL

1.65mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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