MS41
Based on 1 Customer Validation
MS41 is a ENL PROTAC degrader with a DC50 of 3.50 nM. MS41 recruits the VHL E3 ubiquitin ligase, triggers ENL degradation via the ubiquitin-proteasome system, and simultaneously induces AF9 degradation. MS41 reduces the chromatin occupancy of ENL-associated transcription elongation complexes, suppresses oncogene expression, and activates differentiation gene expression. MS41 inhibits leukemia cell growth and induces cell cycle arrest and apoptosis. MS41 inhibits leukemia progression in xenograft mouse models. MS41 can be used for research on mixed lineage leukemia-rearranged leukemia and nephroblastoma.
(Pink: ENL ligand (HY-169094); Blue: VHL ligand (HY-112078); Black: linker (HY-W105744)).
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 純度: 98.97%
- CAS 番号: 2768610-97-3
- 分子式: C56H70N8O9S
- 分子量:1031.27
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保管条件: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]
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生物活性
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化学情報
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溶剤 & 溶解度
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
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生物活性
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VHL |
ENL 2.84 nM (DC50) |
MS41 (0.1 nM-54 μM; 1 hour) potently inhibits the ENL YEATS domain-H3K9ac interaction with an IC50 of 119.43 nM, binds comparably to AF9 YEATS domain, and does not bind GAS41 or YEATS2 YEATS domains[1].
MS41 (0.25-256 nM; 24 hours) 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 and >99% maximal degradation[1].
MS41 (0.25-256 nM; 24 hours) potently and rapidly degrades ENL in SEMK2, Jurkat, and KASUMI1 human leukemia cells, with DC50 values ranging from 2.84 to 26.58 nM and >93% maximal degradation[1].
MS41 is a highly selective ENL degrader in MV4;11 cells, with no detectable off-target protein degradation at the proteome-wide level[1].
MS41 (6 days, 12 days for Jurkat and K-562) potently inhibits proliferation of ENL-dependent human leukemia cell lines (MV4;11, RS4;11, SEMK2, KASUMI1) with GI50 values ranging from 21.28 to 406.46 nM, while having no effect on non-ENL-dependent Jurkat and K-562 cells[1].
MS41 (100 nM; 7-10 days) impairs the clonogenic potential of ENL-dependent human leukemia cell lines MV4;11, SEMK2, and KASUMI1, but not non-ENL-dependent Jurkat cells[1].
MS41 (10-300 nM; 24 h) suppresses ENL-dependent oncogenic gene expression programs in MV4;11 cells, down-regulating key leukemia-associated genes and up-regulating myeloid differentiation markers, with effects matching those of ENL knockout[1].
MS41 (100 nM; 6, 24 hours) reduces chromatin occupancy of ENL and its associated transcription elongation machinery (SEC, DOT1L, elongating Pol II) on target genes, leading to suppressed gene expression in MV4;11 cells[1].
MS41 (1-1000 nM; 24, 72 hours) potently degrades wild-type and YEATS domain mutant ENL proteins and suppresses the aberrant HOXA gene expression induced by mutant ENL in HEK293 cells[1].
MS41 (100 nM; 24-72 hours) induces time-dependent G1 cell cycle arrest and apoptosis in MV4;11 human leukemia cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human MLL-r leukemia cell line MV4;11
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Concentration:0.25, 0.5, 1, 2, 4, 8, 16, 32, 64, 128, 256 nM (24-hour treatment)
100 nM (washout and mechanism validation)
0, 0.2, 1, 5 μM PFI-6 (HY-155412), VH298 (HY-100947), MG132 (HY-13259) (pretreatment)
0, 0.1, 0.3, 1 μM MLN4924 (HY-70062) (pretreatment) -
Incubation Time:24 hours (concentration-dependent degradation)
0.5, 1, 2, 6, 12, 24, 48, 72 hours (washout)
2 hours (MS41 treatment with 1-hour pretreatment) -
Result:Induced concentration-dependent ENL degradation with a DC50 of 3.50 nM and Dmax of 99.8%.
Induced rapid ENL degradation detected as early as 30 minutes, maximal at 6 hours with 100 nM MS41.
Restored ENL levels by 6 hours and fully restored by 12 hours after washout.
Blocked MS41-mediated ENL degradation in a concentration-dependent manner with pretreatment of PFI-6, VH298, MG132, or MLN4924.
Completely abolished MS41-induced ENL degradation with CRISPR-Cas9-mediated VHL ablation.
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Cell Line:human leukemia cell lines SEMK2, Jurkat, KASUMI1
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Concentration:0.25, 0.5, 1, 2, 4, 8, 16, 32, 64, 128, 256 nM (24-hour treatment)
100 nM (time-course) -
Incubation Time:24 hours (concentration-dependent degradation)
0.5, 1, 2, 6, 12, 24, 48, 72 hours (time-course) -
Result:Induced concentration-dependent ENL degradation with DC50 values of 2.84 nM (SEMK2), 3.03 nM (Jurkat), and 26.58 nM (KASUMI1), with Dmax > 93% across all cell lines.
Induced rapid ENL degradation detected as early as 30 minutes, maximal at 6 hours with 100 nM MS41.
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Cell Line:human MLL-r leukemia cell line MV4;11
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Concentration:100 nM
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Incubation Time:24, 48, 72 h
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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.
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Cell Line:human MLL-r leukemia cell line MV4;11
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Concentration:100 nM
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Incubation Time:24, 48, 72 h
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Result:Induced time-dependent apoptosis in MV4;11 human leukemia cells.
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Cell Line:human MLL-r leukemia cell line MV4;11
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Concentration:10, 30, 100, 300 nM
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Incubation Time:24 h
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Result:Suppressed ENL-dependent oncogenic gene expression programs in MV4;11 cells, down-regulating key leukemia-associated genes and up-regulating myeloid differentiation markers.
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Cell Line:human MLL-r leukemia cell line MV4;11
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Concentration:100 nM
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Incubation Time:6, 24 hours
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Result:Reduced chromatin occupancy of ENL and its associated transcription elongation machinery (SEC, DOT1L, elongating Pol II) on target genes, leading to suppressed gene expression in MV4;11 cells.
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Cell Line:HEK293 cells
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Concentration:100 nM
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Incubation Time:72 h
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Result:Suppressed the aberrant HOXA gene expression induced by mutant ENL in HEK293 cells.
| 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.
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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]
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Dosage:50 mg/kg
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Administration:i.p.; once daily; starting 10 days post-transplant until study endpoint
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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.
Drastically reduced bioluminescent signals (leukemia burden).
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.
化学情報
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CAS 番号 2768610-97-3
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性状 Solid
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分子量 1031.27
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分子式 C56H70N8O9S
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Color White to off-white
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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
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
溶剤 & 溶解度
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.
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
純度とドキュメンテーション
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データシート (283 KB)
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SDS (254 KB)
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取扱説明書 (2659 KB)
参考文献
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 関連分類
HY-169093 関連分類
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