| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
| Targets |
MS1943 targets EZH2 (enhancer of zeste homolog 2), a histone-lysine N-methyltransferase that is the catalytic subunit of the polycomb repressive complex 2 (PRC2). EZH2 methylates histone H3 at lysine 27 (H3K27me3), leading to transcriptional repression of target genes. MS1943 acts as a selective degrader, reducing EZH2 protein levels through targeted protein degradation.
|
|---|---|
| ln Vitro |
MS1943 (0.625-5 μM; 3 days) inhibits cell growth with a GI50 of 2.2 µM[1]. MDA-MB-468 cells are exposed to MS1943 (0.625-5 μM; 4 days), which causes cell death. The TNBC cells BT549, HCC70, and MDA-MB-231, the lymphoma cells KARPAS-422 and SUDHL8, and the non-cancerous prostate cells PNT2 all exhibit effective reductions in EZH2 levels when exposed to MS1943[1]. Without influencing EED protein levels, MS1943 (1.25-5.0 μM; 2 days) suppresses the H3K27me3 mark and inhibits EZH2 and SUZ12 protein levels in a concentration- and time-dependent manner[1].
In vitro, MS1943 effectively reduces EZH2 protein levels in many triple-negative breast cancer and other cancer cell lines. It inhibits EZH2 methyltransferase activity with an IC50 of 120 nM. MS1943 effectively blocks the proliferation of multiple TNBC and other cancer cell lines. Its mechanism of action involves selective degradation of EZH2. |
| ln Vivo |
Tumor development is suppressed by MS1943 (150 mg/kg body weight; ip; once daily for 36 days)[1]. MS1943 causes the MDA-MB-468 xenograft model to undergo apoptosis[1]. A single intraperitoneal (i.p.) injection of MS1943 at a dose of 50 mg/kg body weight produced plasma concentrations above its cellular IC50 value for approximately two hours, with a peak plasma concentration (Cmax) of 2.9 µM. A single dose of 150 mg/kg body weight po produced a Cmax of 1.1 µM; however, the cellular IC50 value was not reached by the plasma concentrations[1].
In vivo, MS1943 is an orally bioavailable EZH2 selective degrader. As an orally bioavailable compound, it can be administered to animal models of cancer. Its ability to degrade EZH2 and inhibit tumor cell proliferation translates to in vivo efficacy. MS1943 has been studied in preclinical models of triple-negative breast cancer and other cancers. |
| Enzyme Assay |
In vitro enzyme assays for MS1943 involve measuring its inhibition of EZH2 methyltransferase activity. Recombinant EZH2 is incubated with increasing concentrations of the compound, S-adenosylmethionine (SAM), and a peptide substrate. The methylation of histone H3 lysine 27 (H3K27me3) is measured by ELISA or by using radiolabeled SAM. IC50 values are calculated from dose-response curves.
|
| Cell Assay |
Cell Viability Assay[1]
Cell Types: MDA-MB-468 cells Tested Concentrations: 0.625, 1.25, 2.5, 5 μM Incubation Duration: 3 days Experimental Results: Inhibits cell growth with an GI50 of 2.2 µM. Western Blot Analysis[1] Cell Types: MDA-MB-468 cells Tested Concentrations: 1.25, 2.5, 5.0 µM Incubation Duration: 2 days Experimental Results: decreased EZH2 protein levels in a concentration- and time-dependent manner. For in vitro cell-based assays, cancer cell lines (e.g., TNBC cells) are cultured and treated with MS1943 at various concentrations. EZH2 protein levels are measured by Western blot. H3K27me3 levels are assessed by Western blot or ELISA. Cell proliferation is assessed by MTT or CellTiter-Glo assays. Cell cycle analysis and apoptosis are evaluated by flow cytometry. |
| Animal Protocol |
Animal/Disease Models: Eightweeks old female BALB/c nude mice (MDA-MB-468 xenografts)[1]
Doses: 150 mg/kg body weight Route of Administration: ip; one time/day for 36 days Experimental Results: Suppresses tumor growth. In vivo animal studies with MS1943 are conducted in mouse xenograft models of cancer. Tumor-bearing mice are treated with the compound orally at doses determined from pharmacokinetic studies. Tumor growth inhibition is monitored. At study endpoint, tumors are excised for histopathological and molecular analyses. EZH2 and H3K27me3 levels in tumors are measured by Western blot or immunohistochemistry. |
| ADME/Pharmacokinetics |
MS1943 (CAS: 2225938-17-8) has a molecular weight of 718.93 g/mol and a molecular formula of C42H54N8O3. Appearance: solid powder. Purity: ≥98%. Solubility: DMSO. Storage: powder at -20°C. The compound is a first-in-class, orally bioavailable EZH2 selective degrader.
|
| Toxicity/Toxicokinetics |
MS1943 is a research compound and is not approved for human therapeutic use. In preclinical studies, it has shown a manageable safety profile. As an EZH2 degrader, it may affect normal cellular processes regulated by PRC2. The compound's selectivity for EZH2 over other proteins may reduce off-target effects. Standard laboratory safety precautions should be followed when handling the compound.
|
| References | |
| Additional Infomation |
MS1943 is a first-in-class, orally bioavailable selective EZH2 degrader. It effectively reduces EZH2 protein levels in many triple-negative breast cancer and other cancer cell lines, and inhibits EZH2 methyltransferase activity with an IC50 of 120 nM. It has a molecular weight of 718.93 g/mol and a molecular formula of C42H54N8O3. It is not FDA-approved and is intended for research use only.
|
| Molecular Formula |
C42H54N8O3
|
|---|---|
| Molecular Weight |
718.9300
|
| Exact Mass |
718.431
|
| CAS # |
2225938-17-8
|
| PubChem CID |
139211327
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
5.7
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
11
|
| Heavy Atom Count |
53
|
| Complexity |
1410
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C(C([H])([H])C12C([H])([H])C3([H])C([H])([H])C([H])(C([H])([H])C([H])(C3([H])[H])C1([H])[H])C2([H])[H])N([H])C([H])([H])C([H])([H])N1C([H])([H])C([H])([H])N(C2C([H])=C([H])C(C3=C([H])C(C(N([H])C([H])([H])C4C(N([H])C(C([H])([H])[H])=C([H])C=4C([H])([H])[H])=O)=O)=C4C([H])=NN(C([H])(C([H])([H])[H])C([H])([H])[H])C4=C3[H])=C([H])N=2)C([H])([H])C1([H])[H]
|
| InChi Key |
WQIQJFXBAJJKNT-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C42H54N8O3/c1-26(2)50-37-18-33(17-34(36(37)25-46-50)40(52)45-24-35-27(3)13-28(4)47-41(35)53)32-5-6-38(44-23-32)49-11-9-48(10-12-49)8-7-43-39(51)22-42-19-29-14-30(20-42)16-31(15-29)21-42/h5-6,13,17-18,23,25-26,29-31H,7-12,14-16,19-22,24H2,1-4H3,(H,43,51)(H,45,52)(H,47,53)
|
| Chemical Name |
6-[6-[4-[2-[[2-(1-adamantyl)acetyl]amino]ethyl]piperazin-1-yl]pyridin-3-yl]-N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-1-propan-2-ylindazole-4-carboxamide
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~173.87 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (8.69 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 6.25 mg/mL (8.69 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 6.25 mg/mL (8.69 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3910 mL | 6.9548 mL | 13.9096 mL | |
| 5 mM | 0.2782 mL | 1.3910 mL | 2.7819 mL | |
| 10 mM | 0.1391 mL | 0.6955 mL | 1.3910 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
