| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
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| Other Sizes |
| Targets |
- NSD2 (in vitro IC50 = 111 ± 11 µM for H3K36 mono-methylation). [1]
- NSD1 (in vitro IC50 = 418 ± 111 µM). [1] - NSD3 (in vitro IC50 = 60 ± 11 µM). [1] 418 μM (NSD1), 111 μM (NSD2), and 60 μM (NSD3)[1] NSD1, NSD2, NSD3 (Nuclear receptor-binding SET domain-containing proteins) |
|---|---|
| ln Vitro |
- Enzymatic Inhibition: LEM-14-1189 differentially inhibits the NSDs with in vitro IC50 values of 418 µM (NSD1), 111 µM (NSD2), and 60 µM (NSD3) for H3K36 mono-methylation. In contrast to LEM-14, which is only active on NSD2, LEM-14-1189 inhibits NSD3 and NSD1. [1]
- Binding Affinity (in silico): Molecular docking studies predicted that LEM-14-1189 binds to the histone-tail site and the coenzyme (AdoMet) site of NSD1, NSD2, and NSD3. Docking affinities (kcal/mol): NSD1 (histone-tail site: -13.2; AdoMet site: -10.1), NSD2 (-10.9; -11.7), NSD3 (-12.8; -15.0). The lowest docking energy (-15.0 kcal/mol) was observed for binding to the coenzyme pocket of NSD3. [1] The compound shows inhibitory activity against NSD family histone lysine methyltransferases, with IC50 values of 418 microM for NSD1, 111 microM for NSD2, and 60 microM for NSD3. Its primary selectivity is for NSD3, making it a useful tool for dissecting NSD3-specific functions. |
| ln Vivo |
No standardized in vivo data is available. As an NSD inhibitor, it shows potential for studying the role of these histone methyltransferases in tumorigenesis, particularly multiple myeloma where NSD2 is frequently dysregulated, as well as other hematologic malignancies.
|
| Enzyme Assay |
- Histone Methyltransferase Activity Assay for IC50: The methyltransferase activity of the NSD1-SET, NSD2-SET, and NSD3-SET domains was measured using a Methyltransferase Activity Assay kit. These assays were performed to determine the dose-response curve for LEM-14-1189 on the mono-methylation of H3K36. Assays were conducted in triplicate individual experiments. Results were normalized against a control that did not contain any enzymes. IC50 values were calculated by processing the data and plotting dose-response curves using graphing software. [1]
The in vitro enzymatic assay uses recombinant NSD SET domain proteins and a biotinylated histone H3 peptide substrate. After incubating with the compound and 3H-SAM as a methyl donor, the reaction is captured on streptavidin-coated plates. Radioactivity is measured to determine inhibition. |
| Cell Assay |
Histone methyltransferase assays are performed in cellular contexts. Cells are treated with the compound for 24-72 hours. Histones are extracted, separated by SDS-PAGE, and probed with modification-specific antibodies (e.g., H3K36me2) to evaluate inhibition of methylation by Western blotting.
|
| Animal Protocol |
No specific animal protocol is documented. Typically, mice bearing xenograft tumors are treated with varying doses of the compound via oral gavage or intraperitoneal injection. Tumor growth is measured, and tumor tissue is analyzed for target engagement via histone methylation status.
|
| ADME/Pharmacokinetics |
Comprehensive PK data is not publicly available. The compound is described as having good ADME (absorption, distribution, metabolism, and excretion) properties as part of its chemical design, suggesting potential for favorable pharmacokinetics.
|
| Toxicity/Toxicokinetics |
No formal toxicity data is publicly available. Given its micromolar potency, therapeutic indices may require careful evaluation. Preliminary studies would need to assess maximum tolerated doses and potential off-target epigenetic effects.
|
| References | |
| Additional Infomation |
- Chemical Properties: LEM-14-1189 has a molecular weight of 683.8 Da, a total polar surface area (TPSA) of 141.5 Ų, a calculated octanol/water partition coefficient (cLogP) of 1.1, 9.72 rotatable bonds, and 2 violations of Lipinski's Rule of 5. [1]
- Binding Mechanism (in silico): Molecular modeling suggests that, unlike LEM-14, LEM-14-1189 extends into the narrow lysine channel of NSD3 when bound to the active site. In NSD2, it appears to bind preferentially to the coenzyme site and is anchored tighter than LEM-14, with stabilization by hydrogen bonds to Lys1069, Trp1075, Thr1115, and Arg1192. The tighter interaction network of LEM-14-1189 with NSD3 explains its selective inhibition of NSD3 over NSD1 and NSD2. [1] - Proposed Use: The authors propose LEM-14-1189 as a tool for investigating the biology of the NSDs and for the further development of specific NSDs inhibitors suitable for treating malignancies including multiple myeloma. [1] This compound is an active biochemical for research purposes, specifically designed to inhibit NSD histone methyltransferases. It has not been approved for human clinical use by any regulatory agency and is strictly for investigational use. |
| Molecular Formula |
C35H34N6O5S2
|
|---|---|
| Molecular Weight |
682.81
|
| Exact Mass |
682.203210
|
| CAS # |
2987501-17-5
|
| Appearance |
White to off-white solid powder
|
| LogP |
5.3
|
| SMILES |
C1CCC2=C(C1)C3=C(S2)N=C(NC3=O)CN(CCCNC(=O)C4=CC5=CC=CC=C5C(=O)O4)CC6=NC7=C(C8=C(S7)CCCC8)C(=O)N6
|
| InChi Key |
YLIXLTMOWMXIPA-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C35H34N6O5S2/c42-30(23-16-19-8-1-2-9-20(19)35(45)46-23)36-14-7-15-41(17-26-37-31(43)28-21-10-3-5-12-24(21)47-33(28)39-26)18-27-38-32(44)29-22-11-4-6-13-25(22)48-34(29)40-27/h1-2,8-9,16H,3-7,10-15,17-18H2,(H,36,42)(H,37,39,43)(H,38,40,44)
|
| Chemical Name |
N-[3-[bis[(4-oxo-5,6,7,8-tetrahydro-3H-[1]benzothiolo[2,3-d]pyrimidin-2-yl)methyl]amino]propyl]-1-oxoisochromene-3-carboxamide
|
| Synonyms |
LEM-14-1189; 2987501-17-5; LEM14-1189; CHEMBL5416266; LEM-141189; orb1744526; BDBM50629737;
|
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4645 mL | 7.3227 mL | 14.6454 mL | |
| 5 mM | 0.2929 mL | 1.4645 mL | 2.9291 mL | |
| 10 mM | 0.1465 mL | 0.7323 mL | 1.4645 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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