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Chemical Structure| 2225938-17-8 Chemical Structure| 2225938-17-8

Structure of MS1943
CAS No.: 2225938-17-8

Chemical Structure| 2225938-17-8

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MS1943 is a first-in-class EZH2 selective degrader that effectively reduces EZH2 levels in cells.

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Product Details of MS1943

CAS No. :2225938-17-8
Formula : C42H54N8O3
M.W : 718.93
SMILES Code : O=C(NCC=1C(=O)NC(=CC1C)C)C2=CC(=CC3=C2C=NN3C(C)C)C=4C=NC(=CC4)N5CCN(CCNC(=O)CC67CC8CC(CC(C8)C6)C7)CC5
MDL No. :MFCD32671554
InChI Key :WQIQJFXBAJJKNT-UHFFFAOYSA-N
Pubchem ID :139211327

Safety of MS1943

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of MS1943

epigenetics
GPCR

Isoform Comparison

Biological Activity

Description
MS1943 represents a pioneering orally bioavailable EZH2 selective degrader, demonstrating an IC50 value of 120 nM. It notably diminishes EZH2 protein levels across various triple-negative breast cancer (TNBC) and other cancer and noncancerous cell lines. Additionally, MS1943 robustly impedes the proliferation of multiple TNBC and other cancer cell lines[1].

In Vitro:

Cell Line
Concentration Treated Time Description References
Daudi cells 2.5 μM, 5 μM, 10 μM 24 hours, 48 hours, 72 hours To evaluate the inhibitory effects of MS1943 on the proliferation of Burkitt's lymphoma cells, the results showed that MS1943 significantly inhibited cell proliferation at 24, 48, and 72 hours in a dose-dependent manner. Front Oncol. 2023 Sep 11;13:1252658
Ramos cells 2.5 μM, 5 μM, 10 μM 24 hours, 48 hours, 72 hours To evaluate the inhibitory effects of MS1943 on the proliferation of Burkitt's lymphoma cells, the results showed that MS1943 significantly inhibited cell proliferation at 24, 48, and 72 hours in a dose-dependent manner. Front Oncol. 2023 Sep 11;13:1252658
RPMI1788 cells 2.5 μM, 5 μM, 10 μM 24 hours, 48 hours, 72 hours To evaluate the inhibitory effects of MS1943 on the proliferation of Burkitt's lymphoma cells, the results showed that MS1943 significantly inhibited cell proliferation at 24, 48, and 72 hours in a dose-dependent manner. Front Oncol. 2023 Sep 11;13:1252658
MCF7 cells 4 μM 48 hours To evaluate the effect of MS1943 on EZH2 protein levels, results showed that MS1943 significantly reduced EZH2 protein levels Nat Chem Biol. 2020 Feb;16(2):214-222
PNT2 cells 4 μM 48 hours To evaluate the effect of MS1943 on EZH2 protein levels, results showed that MS1943 significantly reduced EZH2 protein levels Nat Chem Biol. 2020 Feb;16(2):214-222
SUDHL8 cells 4 μM 48 hours To evaluate the effect of MS1943 on EZH2 protein levels, results showed that MS1943 significantly reduced EZH2 protein levels Nat Chem Biol. 2020 Feb;16(2):214-222
KARPAS-422 cells 4 μM 48 hours To evaluate the effect of MS1943 on EZH2 protein levels, results showed that MS1943 significantly reduced EZH2 protein levels Nat Chem Biol. 2020 Feb;16(2):214-222
MDA-MB-231 cells 4 μM 48 hours To evaluate the effect of MS1943 on EZH2 protein levels, results showed that MS1943 significantly reduced EZH2 protein levels Nat Chem Biol. 2020 Feb;16(2):214-222
HCC70 cells 4 μM 6-48 hours To evaluate the effect of MS1943 on EZH2 protein levels, results showed that MS1943 significantly reduced EZH2 protein levels Nat Chem Biol. 2020 Feb;16(2):214-222
BT549 cells 4 μM 48 hours To evaluate the effect of MS1943 on EZH2 protein levels, results showed that MS1943 significantly reduced EZH2 protein levels Nat Chem Biol. 2020 Feb;16(2):214-222
MDA-MB-468 cells 5 μM 24-48 hours To evaluate the effect of MS1943 on EZH2 protein levels, results showed that MS1943 significantly reduced EZH2 and SUZ12 protein levels Nat Chem Biol. 2020 Feb;16(2):214-222
B16-F10 cells 2 μM 3 days MS1943 simultaneously reduced EZH2 and H3K27me3, and upregulated MITF. Similar to effects of siEZH2 and DZNep, MS1943-treated cells showed higher melanin content, greater senescence and reduced clonogenicity. Oncogene. 2023 Apr;42(17):1360-1373
Daudi cells 2.5 µM, 5 µM, 10 µM 24, 48, 72 hours MS1943 inhibited Daudi cell proliferation Cancers (Basel). 2023 Sep 8;15(18):4472
Ramos cells 2.5 µM, 5 µM, 10 µM 24, 48, 72 hours MS1943 inhibited Ramos cell proliferation Cancers (Basel). 2023 Sep 8;15(18):4472

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice MDA-MB-468 xenograft model Intraperitoneal injection 150 mg/kg Once daily for 36 days To evaluate the antitumor activity of MS1943 in vivo, results showed that MS1943 completely suppressed tumor growth Nat Chem Biol. 2020 Feb;16(2):214-222

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.39mL

0.28mL

0.14mL

6.95mL

1.39mL

0.70mL

13.91mL

2.78mL

1.39mL

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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