| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
PRMT5 (protein arginine methyltransferase 5). DW14800 is an inhibitor of PRMT5, an enzyme that catalyzes symmetric dimethylation of arginine residues on histones and other proteins. PRMT5 plays a role in transcriptional repression, splicing, and cancer. DW14800 reduces H4R3me2s levels and enhances HNF4alpha transcription.
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| ln Vitro |
DW14800 inhibits PRMT5 with an IC₅0 of 17 nM. It reduces H4R3me2s levels and enhances the transcription of HNF4alpha, but does not alter PRMT5 expression. The compound exhibits anticancer activity. HNF4alpha is a transcription factor involved in liver development, metabolism, and cancer, and its upregulation may contribute to the compound's anticancer effects.
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| ln Vivo |
In vivo, DW14800 would be expected to demonstrate antitumor efficacy in cancer models. By inhibiting PRMT5 and reducing H4R3me2s levels, the compound modulates gene expression and suppresses tumor growth. Efficacy would be assessed in xenograft models of PRMT5-dependent cancers (e.g., mantle cell lymphoma, lung cancer, breast cancer).
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| Enzyme Assay |
PRMT5 enzymatic activity is measured using a radiometric or fluorescence-based methyltransferase assay. Recombinant PRMT5 is incubated with a histone H4 peptide substrate and S-adenosylmethionine (SAM, the methyl donor) in the presence of serial dilutions of test compound. Incorporation of methyl groups into the substrate is quantified, and IC₅0 values are calculated from dose-response curves.
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| Cell Assay |
Cancer cell lines (e.g., mantle cell lymphoma, lung cancer, breast cancer) are treated with DW14800 at various concentrations for 48-72 hours. H4R3me2s levels are assessed by Western blotting. HNF4alpha mRNA and protein levels are measured by qPCR and Western blotting. Cell viability is assessed using MTT or CellTiter-Glo assays. Apoptosis and cell cycle changes are evaluated by flow cytometry.
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| Animal Protocol |
Mice bearing subcutaneous tumor xenografts are administered DW14800 orally or intraperitoneally. Tumor growth is monitored by caliper measurements. Tumors are harvested for pharmacodynamic analysis of PRMT5 inhibition (H4R3me2s levels), HNF4alpha expression, and apoptosis markers. Efficacy is determined by tumor growth inhibition.
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| ADME/Pharmacokinetics |
DW14800 has a molecular weight of 512.64 g/mol and formula C31H3₆N4O3. Standard PK parameters (half-life, Cmax, AUC, clearance, volume of distribution, oral bioavailability) would be determined in rodent studies following IV and PO administration. The compound is soluble in DMSO and formulated in suitable vehicles for in vivo administration.
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| Toxicity/Toxicokinetics |
Toxicology data for DW14800 are not publicly available. Standard preclinical safety assessment would include cytotoxicity screening, hERG testing, and repeat-dose toxicology studies in rodents. Given PRMT5's role in normal cellular processes, potential on-target toxicities would be evaluated.
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| References | |
| Additional Infomation |
DW14800 is a research compound for studying PRMT5 biology and cancer. It is not clinically approved. The compound's ability to enhance HNF4alpha transcription while inhibiting PRMT5 provides a unique mechanistic profile. DW14800 is useful for investigating the role of PRMT5 in cancer and for developing novel epigenetic therapies.
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| Molecular Formula |
C31H36N4O3
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|---|---|
| Molecular Weight |
512.64
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| Exact Mass |
512.278
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| CAS # |
2243709-60-4
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| PubChem CID |
138454790
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| Appearance |
White to off-white solid powder
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| LogP |
3.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
38
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| Complexity |
798
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1C2=C(C=C(C(NCC(O)CN3CCC4=C(C3)C=CC=C4)=O)C=C2)CCN1C(=O)C1=CC=C(N(C)C)C=C1
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| InChi Key |
MQBNHAAEDHNZCH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C31H36N4O3/c1-33(2)28-11-9-23(10-12-28)31(38)35-16-14-24-17-25(7-8-27(24)20-35)30(37)32-18-29(36)21-34-15-13-22-5-3-4-6-26(22)19-34/h3-12,17,29,36H,13-16,18-21H2,1-2H3,(H,32,37)
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| Chemical Name |
N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-2-(4-(dimethylamino)benzoyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide
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| Synonyms |
DW-14800 DW14800 DW 14800
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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 (~195.07 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.88 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. 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 (4.88 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 to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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 (4.88 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 | 1.9507 mL | 9.7534 mL | 19.5069 mL | |
| 5 mM | 0.3901 mL | 1.9507 mL | 3.9014 mL | |
| 10 mM | 0.1951 mL | 0.9753 mL | 1.9507 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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