Art. -Nr.: HY-173422

MS2133

MS2133 is a VHL-recruiting DOT1L PROTAC degrader. MS2133 possesses antiproliferative activity with a human DOT1L IC₅₀ of 4.6 nM, forms a ternary complex with DOT1L and VHL E3 ligase to drive DOT1L ubiquitination and subsequent proteasomal degradation without affecting DOT1L mRNA transcription, inhibits the proliferation of mixed lineage leukemia-rearranged leukemia cells and downregulates H3K79Me2, restrains proliferation of both tumor and normal cells but lacks cytotoxicity against normal cells, and can be used for the research of mixed lineage leukemia-rearranged leukemia.
(Pink: DOT1L ligand (HY-173423); Blue: VHL ligand (HY-47070); Black: linker).

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Formel: C₅₈H₆₆ClF₃N₁₄O₁₁S₂
Molecular Weight:1291.81

Speicherung:

Please store the product under the recommended conditions in the Certificate of Analysis.

Data Sheet (285 KB)

MS2133 Chemical Structure

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Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- In Vitro
Chemical Information
Reinheit & Dokumentation
Verweise
Calculators
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

MS2133 is a VHL-recruiting DOT1L PROTAC degrader. MS2133 possesses antiproliferative activity with a human DOT1L IC₅₀ of 4.6 nM, forms a ternary complex with DOT1L and VHL E3 ligase to drive DOT1L ubiquitination and subsequent proteasomal degradation without affecting DOT1L mRNA transcription, inhibits the proliferation of mixed lineage leukemia-rearranged leukemia cells and downregulates H3K79Me2, restrains proliferation of both tumor and normal cells but lacks cytotoxicity against normal cells, and can be used for the research of mixed lineage leukemia-rearranged leukemia^[1]. (Pink: DOT1L ligand (HY-173423); Blue: VHL ligand (HY-47070); Black: linker).

IC₅₀ & Target

DOT1L

4.6 nM (IC₅₀)

Alle PROTACs Isoform-spezifische Produkte anzeigen :

Alle Histone Methyltransferase Isoform-spezifische Produkte anzeigen :

In Vitro

MS2133 (compound 13) (0.3-3 μM; 24 h) potently reduces DOT1L protein levels in THP-1 MLL-r leukemia cells, achieving 70% degradation at 0.3 μM and 77% degradation at 3 μM after 24 h treatment^[1].
MS2133 (0.5nM-3.3 μM; 24 h) induces potent concentration-dependent DOT1L degradation in THP-1 cells (DC₅₀ = 56 nM, D_max = 69%) after 24 h treatment^[1].
MS2133 (0.2 nM-3.0 μM; 24 h) induces potent concentration-dependent DOT1L degradation in MV4-11 cells (DC₅₀ = 25 nM, D_max = 93%) after 24 h treatment^[1].

MS2133 (3 μM; 1-48 h) induces time-dependent DOT1L degradation in THP-1 (maximal at 24 h) and MV4-11 (near-complete at 48 h) MLL-r leukemia cells, with downstream H3K79Me2 reduction delayed relative to DOT1L degradation in both cell lines^[1].
MS2133 (3 μM; 4-8 h) -induced DOT1L degradation in THP-1 MLL-r leukemia cells occurs via the ubiquitin-proteasome system, as pre-treatment with proteasome inhibitor or NEDD8-activating enzyme inhibitor blocks degradation^[1].
MS2133 (3 μM; 24 h) -induced DOT1L degradation in THP-1 MLL-r leukemia cells is VHL-dependent, as co-treatment with a competing VHL ligand blocks degradation^[1].
MS2133 (3 μM; 24 h) does not affect DOT1L mRNA expression in MV4-11 and MOLM-13 MLL-r leukemia cells after 24 h treatment at 3 μM^[1].
MS2133 (0.3-3 μM; 24 h) -induced DOT1L degradation in THP-1 MLL-r leukemia cells requires DOT1L binding^[1].
MS2133 (0.004-3.3 μM) potently inhibits DOT1L methyltransferase activity, achieving >95% inhibition at 4.6 nM^[1].
MS2133 (10 μM) is highly selective for DOT1L, showing no significant inhibition of 12 other tested DNA and protein methyltransferases at 10 μM^[1].
DOT1L degrader (0.3-3 µM; 24 h) induces dose-dependent degradation of DOT1L protein in MOLM-13 cells after 24-hour treatment at 0.3 µM and 3 µM^[1].
MS2133 (3 µM; 24 h) at 3 µM for 24 hours does not significantly alter DOT1L mRNA levels in MOLM-13 cells^[1].
DOT1L degrader (0.3-3 µM; 24 h) induces dose-dependent degradation of DOT1L and reduction of H3K79Me2 in MCF10A cells^[1].
MS2133 (0.23-30.0 µM; 7 days) exhibits minimal antiproliferative activity in MCF10A cells^[1].
DOT1L degrader MS2133 (0.3-3 µM; 24 h) induces dose-dependent degradation of DOT1L (without altering H3K79Me2 levels) in PNT2 cells^[1].
MS2133 (0.12-30.0 µM; 7 days) exhibits minimal antiproliferative activity in PNT2 cells^[1].
MS2133 (30 nM-15 μM; 7 days) potently inhibits growth of DOT1L-dependent MV4-11 (GI₅₀ = 212 nM) and MOLM-13 MLL-r leukemia cells after 7 days of treatment, while showing no toxicity to THP-1 cells or normal MCF10A and PNT2 cells^[1].
MS2133 (0.06-15.0 µM; 7 days) exhibits dose-dependent antiproliferative activity in MOLM-13 cells^[1].
MS2133 (0.01-30.0 µM; 7 days) exhibits dose-dependent antiproliferative activity in THP-1 cells over a 7-day treatment period at concentrations ranging from 0.01 µM to 30.0 µM^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis^[1]

Cell Line:

THP-1 mixed lineage leukemia-rearranged (MLL-r) leukemia cells
Concentration:

0.3 μM, 3 μM
Incubation Time:

24 h
Result:

Reduced DOT1L protein levels by 70% at 0.3 μM relative to DMSO control.
Reduced DOT1L protein levels by 77% at 3 μM relative to DMSO control.

Western Blot Analysis^[1]

Cell Line:

THP-1 and MV4-11 MLL-r leukemia cells
Concentration:

3.3 μM down to ~0.5 nM (3-fold serial dilutions, THP-1); 3 μM down to ~0.2 nM (3-fold serial dilutions, MV4-11)
Incubation Time:

24 h
Result:

Induced DOT1L degradation in THP-1 cells with a DC₅₀ of 56 nM and a D_maxof 69%.
Induced DOT1L degradation in MV4-11 cells with a DC₅₀ of 25 nM and a D_max of 93%.

Western Blot Analysis^[1]

Cell Line:

THP-1 and MV4-11 MLL-r leukemia cells
Concentration:

3 μM
Incubation Time:

1-24 h (THP-1); 1-48 h (MV4-11)
Result:

Substantially reduced DOT1L protein levels in THP-1 cells by 1 h, with maximum degradation at 24 h.
Significantly reduced H3K79Me2 levels in THP-1 cells only after 24 h.
Induced pronounced DOT1L degradation in MV4-11 cells starting at 2 h, with near-complete degradation at 48 h.
Reduced H3K79Me2 levels in MV4-11 cells starting at 2 h, with a substantial reduction at 48 h.

Western Blot Analysis^[1]

Cell Line:

THP-1 MLL-r leukemia cells
Concentration:

3 μM
Incubation Time:

1 h (proteasome inhibitor pre-incubation); 4 h (MS2133 post proteasome inhibitor); 1 h (NEDD8-activating enzyme inhibitor pre-incubation); 8 h (MS2133 post NEDD8-activating enzyme inhibitor)
Result:

Rescued MS2133-mediated DOT1L degradation in THP-1 cells when pre-treated with proteasome inhibitor.
Rescued MS2133-mediated DOT1L degradation in THP-1 cells when pre-treated with NEDD8-activating enzyme inhibitor.

Western Blot Analysis^[1]

Cell Line:

THP-1 MLL-r leukemia cells
Concentration:

3 μM
Incubation Time:

24 h
Result:

Significantly rescued the reduction in DOT1L protein level induced by MS2133 when co-treated with VHL ligand.

Real Time qPCR^[1]

Cell Line:

MV4-11 and MOLM-13 MLL-r leukemia cells
Concentration:

3 μM
Incubation Time:

24 h
Result:

Did not significantly alter DOT1L mRNA levels in MV4-11 and MOLM-13 cells.

Western Blot Analysis^[1]

Cell Line:

THP-1 MLL-r leukemia cells
Concentration:

0.3 μM, 3 μM
Incubation Time:

24 h
Result:

Significantly reduced DOT1L protein levels.
Showed no effect on DOT1L protein levels when using modified negative control compound 17 with disrupted DOT1L binding.
Showed no induction of DOT1L degradation when using existing DOT1L inhibitors (compound 2 and EPZ-5676).

Cell Viability Assay^[1]

Cell Line:

MV4-11, MOLM-13, and THP-1 MLL-r leukemia cells; MCF10A and PNT2 normal cells
Concentration:

30 nM-15 μM (2-fold serial dilutions, MV4-11); serial dilutions (MOLM-13, THP-1, MCF10A, PNT2)
Incubation Time:

7 days
Result:

Significantly inhibited growth of MV4-11 cells with a GI₅₀ of 212 nM.
Inhibited growth of MOLM-13 cells but was less potent than in MV4-11 cells.
Did not inhibit growth of THP-1 cells.
Showed no toxicity in MCF10A and PNT2 normal cells.

Western Blot Analysis^[1]

Cell Line:

MOLM-13
Concentration:

0.3 µM, 3 µM
Incubation Time:

24 h
Result:

Reduced DOT1L protein levels in a dose-dependent manner relative to DMSO control.

Real Time qPCR^[1]

Cell Line:

MOLM-13
Concentration:

3 µM
Incubation Time:

24 h
Result:

Showed no significant difference in DOT1L mRNA levels relative to DMSO control.

Cell Viability Assay^[1]

Cell Line:

MOLM-13
Concentration:

0.06 µM, 0.23 µM, 0.47 µM, 0.94 µM, 1.88 µM, 3.75 µM, 7.50 µM, 15.0 µM
Incubation Time:

7 days
Result:

Reduced normalized cell viability in a dose-dependent manner.

Cell Viability Assay^[1]

Cell Line:

THP-1
Concentration:

0.01 µM, 0.04 µM, 0.12 µM, 0.37 µM, 1.11 µM, 3.33 µM, 10.0 µM, 30.0 µM
Incubation Time:

7 days
Result:

Reduced normalized cell viability in a dose-dependent manner.

Western Blot Analysis^[1]

Cell Line:

MCF10A
Concentration:

0.3 µM, 3 µM
Incubation Time:

24 h
Result:

Reduced DOT1L and H3K79Me2 protein levels in a dose-dependent manner relative to DMSO control.

Cell Viability Assay^[1]

Cell Line:

MCF10A
Concentration:

0.23 µM, 0.47 µM, 0.94 µM, 1.88 µM, 3.75 µM, 7.50 µM, 15.0 µM, 30.0 µM
Incubation Time:

7 days
Result:

Caused minimal reduction in normalized cell viability across tested concentrations.

Western Blot Analysis^[1]

Cell Line:

PNT2
Concentration:

0.3 µM, 3 µM
Incubation Time:

24 h
Result:

Reduced DOT1L protein levels in a dose-dependent manner relative to DMSO control, with no change in H3K79Me2 levels.

Cell Viability Assay^[1]

Cell Line:

PNT2
Concentration:

0.12 µM, 0.23 µM, 0.47 µM, 0.94 µM, 1.88 µM, 3.75 µM, 7.50 µM, 15.0 µM, 30.0 µM
Incubation Time:

7 days
Result:

Caused minimal reduction in normalized cell viability across tested concentrations.

Chemical Information

Molecular Weight 1291.81
Formel C₅₈H₆₆ClF₃N₁₄O₁₁S₂
SMILES

O=C([C@H]1N(C([C@@H](NC(C2(F)CC2)=O)C(C)(C)C)=O)C[C@H](O)C1)N[C@H](C3=CC=C(C4=C(C)N=CS4)C=C3)CC(NCCCCCCNC(COC5=NC(N)=NC(NC6=CC(S(=O)(N)=O)=CC=C6N[C@H](C7=NC=CC=C7Cl)C8=C9OC(F)(F)OC9=CC=C8)=N5)=O)=O
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

Please store the product under the recommended conditions in the Certificate of Analysis.

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (285 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Yim H, et al. Discovery of the first-in-class DOT1L PROTAC degrader. European journal of medicinal chemistry. 2025 Jul 05;291:117595. [Content Brief]

Calculators

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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MS2133

Alle PROTACs Isoform-spezifische Produkte anzeigen

Alle Histone Methyltransferase Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Reinheit & Dokumentation

Verweise

Calculators

Help & FAQs

MS2133 Related Classifications

HY-173422 Related Classifications