MS41
Based on 1 Customer Validation
MS41 is a selective ENL PROTAC degrader with DC50 values of 3.50 nM (MV4;11), 2.84 nM (SEMK2), 3.03 nM (Jurkat) and 26.58 nM (KASUMI1), respectively. MS41 recruits the VHL E3 ubiquitin ligase, induces ubiquitination and degradation of ENL (including mutant ENL carrying mutations in the YEATS domain), and reduces the chromatin occupancy of ENL-associated transcription elongation complexes. MS41 induces G1 phase cell cycle arrest and Apoptosis. MS41 inhibits leukemia progression in xenograft models. MS41 can be used in research related to mixed lineage leukemia-rearranged leukemia and Wilms tumor.
(Pink: ENL ligand (HY-169094); Blue: VHL ligand (HY-112078); Black: linker (HY-W105744)).
Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.
- Pureté: 98.97%
- CAS No.: 2768610-97-3
- Formule: C56H70N8O9S
- Masse moléculaire:1031.27
-
Stockage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Activité biologique
-
Chemical Information
-
Solvant et solubilité
- Pureté et documentation
- Références
-
Help & FAQs
-
Apoptosis Compound Library
HY-L003
-
Epigenetics Compound Library
HY-L005
-
Histone Modification Research Compound Library
HY-L024
-
Anti-Cancer Compound Library
HY-L025
-
Anti-Blood Cancer Compound Library
HY-L079
-
PROTAC Library
HY-L151
-
Highly Selective Activators Library
HY-L159
-
Cell Death Library
HY-L162
-
Anti-Hematopathy Compound Library
HY-L171
-
Bioactive Compound Library Max
HY-L181
-
Bioactive Compound Library
HY-L001
-
Non-Alcoholic Fatty Liver Disease (NAFLD) Compound Library
HY-L199
-
High-Throughput Bioactive Compound Library
HY-L205
Voir tous les produits spécifiques à Isoform PROTACs
More
Activité biologique
|
VHL |
ENL 2.84 nM (DC50) |
MS41 (0.1 nM-54 μM; 1 h) potently inhibits the interaction between the ENL YEATS domain and H3K9ac, with an IC50 of 119.43 nM; it binds to the AF9 YEATS domain with comparable affinity, and does not bind to the YEATS domains of GAS41 or YEATS2[1].
MS41 (0.25-256 nM; 24 h) potently, rapidly and reversibly degrades ENL in MV4;11 cells via a VHL- and ubiquitin-proteasome system-dependent mechanism, with a DC50 of 3.50 nM[1].
MS41 (days 6-12) potently inhibits the proliferation of ENL-dependent leukemia cell lines (MV4;11, RS4;11, SEMK2, KASUMI1), with GI50 values ranging from 21.28 to 406.46 nM, but exerts no effect on ENL-independent Jurkat and K-562 cells[1].
MS41 (100 nM; 24-72 h) induces time-dependent G1 phase cell cycle arrest and apoptosis in leukemia cell line MV4;11[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:MV4;11
-
Concentration:0.25, 0.5, 1, 2, 4, 8, 16, 32, 64, 128, 256 nM
-
Incubation Time:24 h
-
Result:Induced concentration-dependent ENL degradation with a DC50 of 3.50 nM and D_MAX of 99.8%.
-
Cell Line:human leukemia cell lines MV4;11, RS4;11, SEMK2, KASUMI1, Jurkat, K-562
-
Concentration:range of concentrations
-
Incubation Time:6-12 days
-
Result:Exhibited potent concentration-dependent growth inhibition in ENL-dependent cell lines: MV4;11 (GI50 = 21.28 nM), RS4;11 (GI50 = 25.06 nM), SEMK2 (GI50 = 406.46 nM), KASUMI1 (GI50 = 69.05 nM).
Had no significant growth inhibitory effect on non-ENL-dependent cell lines Jurkat and K-562 (GI50 > 50 μM).
-
Cell Line:human MLL-r leukemia cell line MV4;11
-
Concentration:100 nM
-
Incubation Time:24, 48, 72 hours
-
Result:Induced G1 cell cycle arrest in a time-dependent manner, with significant increases in G1-phase cells at 48 and 72 hours.
Increased late apoptosis, with significant increases at 48 and 72 hours.
Showed no such effects with MS41N and PFI-6.
| Species | Dose | Route | Cmax | Plasma Concentration |
|---|---|---|---|---|
| Mice[1] | 50 mg/kg | i.p. | 241.8 nM | >30 nM |
MS41 (50 mg/kg; i.p.; once daily; 30 consecutive days) exhibits no detectable in vivo toxicity in healthy C57BL/6J mice, with only mild, reversible effects on normal hematopoiesis[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:NOD.Cg-Prkdcscid Il2rgtm.Wjl/SzJ (NSG) (6 to 8 weeks old, sublethally irradiated, transplanted with luciferase/turboGFP-expressing MV4;11 cells via tail vein injection)[1]
-
Dosage:50 mg/kg
-
Administration:i.p.; once daily; starting 10 days post-transplant until study endpoint
-
Result:Prolonged median survival to 49.5 days compared to 37 days for vehicle controls.
Reduced percentages of human CD45+ leukemia cells in peripheral blood at days 14, 28, and 35 post-treatment initiation.
Drastically reduced bioluminescent signals (leukemia burden) at days 14 and 21 post-treatment.
Showed minimal leukemia cell infiltration in bone marrow, liver, and spleen compared to extensive infiltration in vehicle controls.
Reduced proliferation of leukemia cells confirmed by Ki-67 staining.
Induced complete ENL degradation in bone marrow leukemia cells.
Chemical Information
-
CAS No. 2768610-97-3
-
Appearance Solid
-
Masse moléculaire 1031.27
-
Formule C56H70N8O9S
-
Color White to off-white
-
SMILES
CC1=C(SC=N1)C2=CC=C(C=C2)[C@@H](NC([C@@H]3C[C@H](CN3C([C@H](C(C)(C)C)NC(CCCCCCCCCNC(C4=CC=C5CC[C@H](C5=C4)NC(C6=NOC(C7=CC(O)=C(C=C7)C(N(C)C)=O)=C6)=O)=O)=O)=O)O)=O)C
-
Livraison
Room temperature in continental US; may vary elsewhere.
-
Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvant et solubilité
DMSO : 100 mg/mL (96.97 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Pureté et documentation
-
Fiche technique (278 KB)
-
SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
-
Instruction de manipulation (2659 KB)
Références
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 0.9697 mL | 4.8484 mL | 9.6968 mL | 24.2420 mL |
| 5 mM | 0.1939 mL | 0.9697 mL | 1.9394 mL | 4.8484 mL | |
| 10 mM | 0.0970 mL | 0.4848 mL | 0.9697 mL | 2.4242 mL | |
| 15 mM | 0.0646 mL | 0.3232 mL | 0.6465 mL | 1.6161 mL | |
| 20 mM | 0.0485 mL | 0.2424 mL | 0.4848 mL | 1.2121 mL | |
| 25 mM | 0.0388 mL | 0.1939 mL | 0.3879 mL | 0.9697 mL | |
| 30 mM | 0.0323 mL | 0.1616 mL | 0.3232 mL | 0.8081 mL | |
| 40 mM | 0.0242 mL | 0.1212 mL | 0.2424 mL | 0.6060 mL | |
| 50 mM | 0.0194 mL | 0.0970 mL | 0.1939 mL | 0.4848 mL | |
| 60 mM | 0.0162 mL | 0.0808 mL | 0.1616 mL | 0.4040 mL | |
| 80 mM | 0.0121 mL | 0.0606 mL | 0.1212 mL | 0.3030 mL |
MS41 Related Classifications
HY-169093 Related Classifications
Powered by Bioz