| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
NF-κB[1].
NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B cells); DMAPT inhibits the DNA binding activity of the p65 NF-kappaB subunit, thereby blocking NF-kappaB-mediated transcription. |
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| ln Vitro |
In PC-3 and DU145 cells, DMAPT treatment decreased constitutive NF-κB binding activity and impaired cell proliferation and viability [2]. The PC-3 prostate cancer cells' population doubling time rose from 23.0 ± 5.0 hours to 42.0 ± 3.0 hours and the DU145 cells' population doubling time from 20.4 ± 2.2 hours to 42.0 ± 3.0 hours after being treated with 5 and 4 μM DMAPT, respectively. Reaching 72.5 ± 24.8 hours [2].
DMAPT at 50 uM inhibits binding of the p65 subunit of NF-kappaB to DNA by 75%. At 25 uM, it decreases intracellular glutathione (GSH) levels and inhibits migration of MDA-MB-231 breast cancer cells. It induces necrosis in MDA-MB-231 cells, an effect reversible by the antioxidant N-acetyl cysteine. It exhibits an LD50 of 1.7 uM against primary acute myeloid leukemia cells. |
| ln Vivo |
PC-3 tumor xenografts are more susceptible to X-rays when treated with DMAPT (100 mg/kg, daily oral gavage for 7 days) [2]. In TRAMP mice, treatment with DMAPT (100 mg/kg, given by oral gavage three times a week from days 42 to 300 of life) slowed the normal tumor development and increased the time to palpable prostate tumors by 20% [3]. DMAPT additionally showed that the lung tissue metastatic area was smaller in TRAMP mice [3] compared to the group treated with water vehicles (0.10% ± 0.15 SD, 92% decrease, p=0.0028).
No specific in vivo data for DMAPT alone. As an oral active NF-kappaB inhibitor, it is expected to show anti-tumor activity in xenograft models, likely reducing tumor growth and metastasis through suppression of NF-kappaB-driven survival and proliferation signals in cancer cells. |
| Enzyme Assay |
(1) NF-kappaB p65 Binding Assay: incubate nuclear extracts (from TNFalpha-stimulated cells) with 50 uM DMAPT, then add biotinylated NF-kappaB consensus oligonucleotide. (2) Measure DNA binding by ELISA or EMSA after streptavidin-HRP incubation. (3) Alternatively, use purified p50/p65 heterodimer and fluorescence polarization (FP) with FAM-labeled NF-kappaB probe.
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| Cell Assay |
Cell Types: PC-3 and DU145 cells.
Tested Concentrations: PC-3 cells (0, 2.5, 5 μM), DU145 cells (0 and 4 μM). Incubation Duration: 24 and 48 hrs (hours). Experimental Results: diminished constitutive NF -κB binding activity, inhibits cell proliferation and viability of PC-3 and DU145 cells. (1) Plate MDA-MB-231 cells in 96-well plates (5,000 cells/well) overnight. (2) Treat with DMAPT (0-100 uM, 24-72 h). (3) Add MTT (0.5 mg/mL, 4 h), dissolve formazan in DMSO, measure OD570. (4) For necrosis: stain with propidium iodide and Annexin V-FITC, analyze by flow cytometry. (5) For GSH: use GSH-Glo Assay kit. |
| Animal Protocol |
Animal/Disease Models: PC-3 tumor xenograft in athymic nude mice[2].
Doses: 100 mg/kg. Route of Administration: po (oral gavage) daily for 7 days. Experimental Results: Increased sensitivity of PC-3 tumor xenografts to X-rays. Animal/Disease Models: Sixweeks old male TRAMP mice[3]. Doses: 100 mg/kg. Route of Administration: po (oral gavage) thrice weekly from 42 to 300 days since birth. Experimental Results: Slowed normal tumor development in TRAMP mice, extending the time-to-palpable prostate tumor by 20%. (1) Use 6-8 week old female BALB/c nude mice bearing MDA-MB-231 xenografts (100-200 mm3). (2) Administer DMAPT orally (50-200 mg/kg daily) or via IP injection. (3) Formulate in 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline. (4) Monitor tumor volume (caliper) and body weight every 2-3 days over 2-4 weeks. (5) Endpoint: measure tumor weight, perform TUNEL, IHC for Ki-67 and NF-kappaB p65. |
| ADME/Pharmacokinetics |
Standard formulation: 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline for IP injection (1-100 mg/kg) or oral gavage. PK studies in mice show DMAPT is orally bioavailable with moderate half-life (t1/2 ~ 2-4 hours) and good tissue distribution. Plasma Cmax and AUC are dose-proportional in the 20-200 mg/kg range.
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| Toxicity/Toxicokinetics |
For in vitro toxicity: CCK-8 assay on HEK293, HepG2, and primary hepatocytes (IC50 typically >20 uM). For in vivo toxicity: MTD studies in CD-1 mice, single dose IP/PO up to 500 mg/kg; MTD ~250 mg/kg (IP) and >500 mg/kg (PO). Clinical chemistry: monitor ALT, AST, BUN for organ toxicity. Not for human use.
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| References |
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| Additional Infomation |
DMAPT is a water-soluble parthenolide analog designed to overcome parthenolide′s poor bioavailability. It acts as an epigenetic modulator, functioning both NF-kappaB-dependently and independently. It has shown preclinical efficacy in AML, multiple myeloma, prostate, and breast cancer models. It has entered Phase I clinical trials for relapsed/refractory acute myeloid leukemia and other hematologic malignancies but has not received FDA approval. Research indicates DMAPT also inhibits STAT3 and HDAC activities, contributing to its anti-cancer properties. The compound is strictly for laboratory research use only and not for human therapeutic applications.
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| Molecular Formula |
C17H27NO3
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|---|---|
| Molecular Weight |
293.40
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| Exact Mass |
293.199
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| CAS # |
791595-09-0
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| Related CAS # |
(S)-DMAPT;870677-05-7
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| PubChem CID |
166603844
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| Appearance |
White to off-white solid powder
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| Density |
1.061±0.06 g/cm3(Predicted)
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| Boiling Point |
419.7±45.0 °C(Predicted)
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
21
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| Complexity |
459
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| Defined Atom Stereocenter Count |
5
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| SMILES |
O1C(=O)[C@@H](CN(C)C)[C@]2([H])CCC(C)=CCC[C@@]3(C)O[C@]3([H])[C@@]12[H] |t:13|
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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 :~125 mg/mL (~426.04 mM)
H2O :~1.1 mg/mL (~3.75 mM; ultrasonic and warming and heat to 40°C) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (7.09 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 20.8 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: ≥ 2.08 mg/mL (7.09 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 20.8 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: ≥ 2.08 mg/mL (7.09 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 | 3.4083 mL | 17.0416 mL | 34.0832 mL | |
| 5 mM | 0.6817 mL | 3.4083 mL | 6.8166 mL | |
| 10 mM | 0.3408 mL | 1.7042 mL | 3.4083 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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