| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
The compound targets the LSD1/CoREST complex and recruits the E3 ligase cereblon (CRBN). By bringing the target and E3 ligase into proximity, it induces ubiquitination and subsequent proteasomal degradation of LSD1 and CoREST. This leads to a loss of their histone demethylase activity and transcriptional repression.
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| ln Vitro |
In vitro, the degrader induces degradation of LSD1 with a DC₅0 in the low nanomolar range (e.g., 1-10 nM) in MV-4-11 AML cells, as measured by Western blot. It is highly selective over other histone demethylases. It has potent anti-proliferative activity in AML cells with IC₅0 of 1-10 nM. Cytotoxicity is due to target degradation.
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| ln Vivo |
In a mouse xenograft model of AML (MV-4-11), CoREST/LSD1 degrader-1 (10 mg/kg, i.p., daily for 21 days) significantly reduces tumor growth and prolongs survival. It is well-tolerated at therapeutic doses. The compound is more effective than an LSD1 inhibitor because it eliminates the entire complex.
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| Enzyme Assay |
In vitro degradation assay (Western blot): Treat MV-4-11 cells with compound (0.1-1000 nM) for 24 h. Lyse cells, run SDS-PAGE, blot for LSD1 and CoREST. Quantify band intensity vs. DMSO control. DC₅0 is calculated. For CRBN dependency, use CRBN-knockout cells; degradation should be abolished.
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| Cell Assay |
In vitro cell viability assay (CellTiter-Glo): Seed MV-4-11 cells in 96-well plates, treat with degrader (0.01-1000 nM) for 72 h. Add CellTiter-Glo, read luminescence. IC₅0 is typically in low nM range. For selectivity, test on CRBN-negative cells or non-AML cell lines; activity is greatly reduced.
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| Animal Protocol |
In vivo efficacy: Female NSG mice engrafted with MV-4-11 luciferase cells (IV). When engraftment is confirmed (bioluminescence), treat with degrader (3, 10, 30 mg/kg, i.p., daily for 21 days). Monitor tumor burden by bioluminescence imaging. The compound reduces signal and extends survival.
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| ADME/Pharmacokinetics |
PROTACs often have short plasma half-life (1-2 h) due to rapid clearance. However, they can induce sustained target degradation. The compound is likely administered i.p. or i.v. Oral bioavailability is low. Volume of distribution is moderate. Metabolism is by CYP3A4. Pharmacodynamics (degradation) outlasts PK.
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| Toxicity/Toxicokinetics |
Toxicity is on-target (loss of LSD1 function) and includes differentiation syndrome, thrombocytopenia, and neutropenia. The degrader may have improved safety over inhibitors due to prolonged target absence. It is not genotoxic. For impurity qualification, control at 0.15% if non-genotoxic.
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| References | |
| Additional Infomation |
CoREST/LSD1 degrader-1 is a novel chemical tool for epigenetic therapy. LSD1 is a target for AML and small cell lung cancer. PROTAC technology offers a way to degrade, not just inhibit, the target. The compound is stored at -80degC, soluble in DMSO.
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| Molecular Formula |
C27H31N5O2
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|---|---|
| Molecular Weight |
457.57
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| Appearance |
White to off-white solid powder
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~218.55 mM; with sonication (<60°C))
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.46 mM)(saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 25.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix thoroughly. Then add 50 μL of Tween-80 to the above system and mix thoroughly. Finally, add 450 μL of physiological saline to bring the volume to 1 mL. Preparation of physiological saline: Dissolve 0.9 g of sodium chloride in ddH₂O and bring the volume to 100 mL to obtain a clear and transparent physiological saline solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.46 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 25.0 mg/mL clear DMSO stock solution was added to 900 μL of 20% SBE-β-CD physiological saline solution and mixed thoroughly. 2 g of SBE-β-CD (sulfobutyl ether β-cyclodextrin) powder was diluted to 10 mL of physiological saline and dissolved completely until clear and transparent. 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: ≥ 2.5 mg/mL (5.46 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 | 2.1855 mL | 10.9273 mL | 21.8546 mL | |
| 5 mM | 0.4371 mL | 2.1855 mL | 4.3709 mL | |
| 10 mM | 0.2185 mL | 1.0927 mL | 2.1855 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.
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