DOT1L705
DOT1L705 is a PROTAC degrader that targets DOT1L. DOT1L705 recruits the VHL E3 ubiquitin ligase to induce proteasomal degradation of DOT1L. DOT1L705 reduces the viability of leukemia cells. DOT1L705 inhibits H3K79 methylation. DOT1L705 can be used in studies related to MLL-rearranged leukemia.
(Pink: DOT1L ligand (HY-135127); Blue: VHL ligand (HY-150802); Black: linker).
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- CAS No.: 3050756-34-5
- Formule: C61H72ClF3N12O13S2
- Masse moléculaire:1337.88
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
Description
In Vitro
DOT1L705 (0.026-1 μM) inhibits H3K79 methylation, reduces viability of MLL-rearranged acute myeloid leukemia cell lines.
DOT1L808 (5-46.6 nM) inhibits H3K79 methylation, reduces viability of MLL-rearranged acute myeloid leukemia cell lines.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:MV-4-11
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Concentration:0-10 μM
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Incubation Time:6 h-96 h
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Result:Induced dose-dependent degradation of DOT1L in MV-4-11 cells with a DC50 of 0.33 μM, achieving near-complete degradation within 4-6 hours (sustained for 96 hours).
Reduced H3K79me2 levels in MV-4-11 cells with an IC50 of 0.026 μM, 13-fold more potent than its effect on DOT1L protein levels.
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Cell Line:MLL-rearranged cell lines
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Concentration:0.01-100 μM
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Incubation Time:5 days
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Result:Selectively inhibited viability of MLL-rearranged cell lines (MV-4-11 IC50 = 0.29 μM; EOL-1 IC50 = 0.39 μM; Pfeiffer IC50 = 0.80 μM) while showing minimal activity against non-MLL-rearranged lines (KG-1 IC50 > 50 μM).
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57 BL/6 female mice ( 7−8 week old)[1]
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Dosage:1 mg/kg (pharmacokinetics); 10 mg/kg (in vivo efficacy)
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Administration:in vitro; i.p. (single dose, pharmacokinetics); i.p. (BID, in vivo efficacy)
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Result:
Reduced tumor volumes by >50% relative to vehicle control in an MV-4-11 subcutaneous xenograft model at 10 mg/kg BID i.p., with no significant body weight loss.
Showed reduced H3K79me2 levels in tumor lysates from the MV-4-11 subcutaneous xenograft model, confirming on-target activity.
Chemical Information
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CAS No. 3050756-34-5
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Masse moléculaire 1337.88
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Formule C61H72ClF3N12O13S2
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SMILES
ClC1=C(N=CC=C1)[C@H](C2=C3OC(F)(OC3=CC=C2)F)NC4=C(C=C(C=C4)S(C)(=O)=O)NC5=NC(N6CCNCC6)=NC(OCCOCCOCCOCCOC7=CC(C8=C(N=CS8)C)=CC=C7CNC([C@@H]9C[C@H](CN9C([C@@H](NC(C%10(CC%10)F)=O)C(C)(C)C)=O)O)=O)=N5
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocole
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Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
DOT1L705 Related Classifications
HY-181787 Related Classifications
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Keywords
- DOT1L705
- 3050756-34-5
- PROTACs
- Histone Methyltransferase
- H3K79 methylation
- orthotopic models
- VHL E3 ubiquitin ligase
- MLL-rearranged acute myeloid leukemia cell lines
- DOT1L
- proteasomal degradation
- MV-4-11 xenograft model
- MLL-rearranged leukemia cells
- menin inhibitor-resistant leukemia cells
- Inhibitor
- inhibitor
- inhibit