| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
- NSD2 (in vitro IC50 = 132 ± 50 µM for H3K36 mono-methylation). [1]
- NSD1 (in vitro IC50 > 1000 µM). [1] - NSD3 (in vitro IC50 = n. a., indicating no inhibitory activity). [1] |
|---|---|
| ln Vitro |
- Enzymatic Inhibition: LEM-14 inhibits NSD2 with an in vitro IC50 of 132 ± 50 µM for H3K36 mono-methylation. It shows very weak activity against NSD1 (IC50 > 1000 µM) and no activity against NSD3. [1]
- Gene Expression Modulation: In bone marrow-derived macrophages (BMDMs) from normal diet (ND) mice, the LEM-14 (100 µM) inhibited the expression of fibrotic genes (Acta2, Col1a1, Col3a1). [3] |
| ln Vivo |
- Wound Healing: In vivo inhibition with LEM-14 blocked normal wound healing in mice at later time points. [3]
|
| Enzyme Assay |
- Histone Methyltransferase Activity Assay for IC50: The histone methyltransferase activity of the NSD2-SET domain on the mono-methylation of H3K36 was measured using a colorimetric quantification kit. Dose-response curves for LEM-14 were generated by following the manufacturer's protocol. The methyltransferase activity of NSD1-SET, NSD2-SET, and NSD3-SET treated with or without LEM-14 was measured using a Methyltransferase Activity Assay kit. Assays were performed in triplicate. Results were normalized against a control without any enzymes. IC50 values were calculated by processing data and plotting dose-response curves with graphing software. [1]
|
| Cell Assay |
- Macrophage Fibrotic Gene Expression: Bone marrow-derived macrophages (BMDMs) were harvested and used for experiments. Cells were treated with LEM-14 (100 µM), and its effect on gene expression was assessed. Wnsc1 knockdown and inhibitor studies were performed in BMDMs. For gene expression analysis, the effect of LEM-14 on TGF-β-dependent expression of fibrotic genes (Acta2, Col1a1, Col3a1) was measured. [3]
|
| Animal Protocol |
- Wound Healing Model: The LEM-14 inhibitor was used to block normal wound healing in an in vivo murine model. Punch biopsies were made in mice. Macrophages were isolated from wounds. The specific inhibitor concentration was 100 µM. Wnsc1 inhibition by LEM-14 was examined for its effect on normal wound healing at later time points. [3]
|
| References |
|
| Additional Infomation |
- Background & Role: NSD2 is a histone methyltransferase. LEM-14 was identified to inhibit NSD2. [1] NSD2 (Wnsc1) has been shown to regulate macrophage to myofibroblast transition during wound healing. LEM-14, as a Wnsc1-specific inhibitor, was used to demonstrate that Wnsc1 is a critical epigenetic switch in tissue repair. [3]
|
| Molecular Formula |
C25H26N4O4S
|
|---|---|
| Molecular Weight |
478.563344478607
|
| Exact Mass |
478.167
|
| Elemental Analysis |
C, 62.74; H, 5.48; N, 11.71; O, 13.37; S, 6.70
|
| CAS # |
1814881-70-3
|
| PubChem CID |
30843512
|
| Appearance |
Light brown to gray solid powder
|
| LogP |
2.9
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
34
|
| Complexity |
873
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
S1C2=C(C(NC(CN3CCN(C([C@H]4CC5C=CC=CC=5C(=O)O4)=O)CC3)=N2)=O)C2=C1CCCC2
|
| InChi Key |
ZJOXWRFJOUWUKX-GOSISDBHSA-N
|
| InChi Code |
InChI=1S/C25H26N4O4S/c30-22-21-17-7-3-4-8-19(17)34-23(21)27-20(26-22)14-28-9-11-29(12-10-28)24(31)18-13-15-5-1-2-6-16(15)25(32)33-18/h1-2,5-6,18H,3-4,7-14H2,(H,26,27,30)/t18-/m1/s1
|
| Chemical Name |
2-[[4-[(3R)-1-oxo-3,4-dihydroisochromene-3-carbonyl]piperazin-1-yl]methyl]-5,6,7,8-tetrahydro-3H-[1]benzothiolo[2,3-d]pyrimidin-4-one
|
| Synonyms |
LEM-14; LEM 14; 1814881-70-3; d]pyrimidin-4(3H)-one; CHEMBL4860876; (R)-2-((4-(1-oxoisochromane-3-carbonyl)piperazin-1-yl)methyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(1H)-one; LEM14
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~104.48 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.22 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0896 mL | 10.4480 mL | 20.8960 mL | |
| 5 mM | 0.4179 mL | 2.0896 mL | 4.1792 mL | |
| 10 mM | 0.2090 mL | 1.0448 mL | 2.0896 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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