| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
IRE1α (inositol-requiring enzyme 1 alpha). The compound inhibits IRE1α oligomerization and its endoribonuclease activity, blocking XBP1 mRNA splicing and downstream XBP1s-dependent signaling.
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|---|---|
| ln Vitro |
3,6-DMAD diHClide (0-6 μM; 24 hours; RPMI 8226 and MM1.R human MM cells) is MM cell line-cytotoxic [1]. In HT1080 cells treated with Tg (0.3 μM), 3,6-DMAD dihydrochloride (0-30 μM; 14 hours) inhibits XBP1 splicing (XBP1s) in a dose-dependent manner [1]. IRE1α endonuclease activity is inhibited by 3,6-DMAD dihydrochloride (0.1-500 μM; 14 hours; HT1080 cells treated with Tg (0.3 μM)) [1]. Inhibiting IRE1α oligomerization and IRE1α-GFP foci formation, 3,6-DMAD dihydrochloride (1-60 μM; 2 hours; HEK293 cells) is one way to treat this [1].
3,6-DMAD diHCl inhibits IRE1α oligomerization and RNase activity with an IC50 of 2.53 μM in cell-free assays. It blocks XBP1 splicing in cells and is used at micromolar concentrations to probe UPR signaling. |
| ln Vivo |
In vivo XBP1 splicing is inhibited by 3,6-DMAD dihydrochloride (10 mg/kg; i.p.; administered three times every 12 hours for 84 hours) in NOD Scid mice bearing RPMI 8226 xenografts [1]. Multiple myeloma xenografts in vivo Graft growth is inhibited by 3,6-DMAD dihydrochloride (10 mg/kg; 24 hours; i.p.; every 48 hours for 12 days; NOD Scid mice using RPMI 8226 xenografts)[1].
In vivo, 3,6-DMAD inhibits XBP1 splicing and the growth of multiple myeloma tumor xenografts. It is a tool compound for studying IRE1α function in cancer and other diseases. |
| Enzyme Assay |
For cell-free IRE1α RNase assays, incubate recombinant IRE1α with a fluorescently labeled XBP1 RNA substrate and serial dilutions of 3,6-DMAD diHCl. Measure cleavage by gel electrophoresis or fluorescence.
|
| Cell Assay |
Cell Viability Assay[1]
Cell Types: RPMI 8226 and MM1.R Human MM Cell Tested Concentrations: 0, 0.5, 1, 2, 3, 4, 5 and 6 μM Incubation Duration: 24 hrs (hours) Experimental Results: Single dose inhibition of cell viability dependent Way. Cell viability assay[1] Cell Types: 0, 5, 10 and 30 μM Tested Concentrations: 0, 0.5, 1, 2, 3, 4, 5 and 6 μM 24 hrs (hours) Incubation Duration: 14 hrs (hours) Experimental Results: Shows XBP1s inhibition as low as 0.5μM . For cell-based assays, treat cells with 3,6-DMAD diHCl (1–50 μM) and measure XBP1s expression by qPCR or Western blot, and IL-6 secretion by ELISA. Include vehicle-treated and IRE1α-knockdown controls. |
| Animal Protocol |
Animal/Disease Models: NOD SCID (severe combined immunodeficient) mouse (4-6 weeks), RPMI 8226 Grafts inhibit XBP1-luciferase activity in NOD SCID (severe combined immunodeficient) mouse.
Animal/Disease Models: NOD SCID (severe combined immunodeficient) mouse (4-6 weeks), RPMI 8226 xenografts [1] Doses: 10 mg/kg Route of Administration: intraperitoneal (ip) injection; every 48 hrs (hrs (hours)) for 12 days Experimental Results: Using RPMI 8226 xenografts The agent inhibits tumor growth in NOD SCID (severe combined immunodeficient) mouse. Administer 3,6-DMAD diHCl intraperitoneally (e.g., 1–10 mg/kg) to mice and assess UPR markers and IL-6 levels in tissues. Include vehicle-treated controls. |
| References |
|
| Molecular Formula |
C22H32CLN5
|
|---|---|
| Molecular Weight |
401.98
|
| Exact Mass |
437.211
|
| CAS # |
2226511-77-7
|
| Related CAS # |
3,6-DMAD hydrochloride
|
| PubChem CID |
165412452
|
| Appearance |
Typically exists as solid at room temperature
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
29
|
| Complexity |
420
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CN(C)CCCNC1=C2C=CC(=CC2=NC3=C1C=CC(=C3)N(C)C)N(C)C.Cl.Cl
|
| InChi Key |
QFTZLLNIVBXXJG-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C22H31N5.2ClH/c1-25(2)13-7-12-23-22-18-10-8-16(26(3)4)14-20(18)24-21-15-17(27(5)6)9-11-19(21)22;;/h8-11,14-15H,7,12-13H2,1-6H3,(H,23,24);2*1H
|
| Chemical Name |
9-N-[3-(dimethylamino)propyl]-3-N,3-N,6-N,6-N-tetramethylacridine-3,6,9-triamine;dihydrochloride
|
| 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
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|---|---|
| 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 | 2.4877 mL | 12.4384 mL | 24.8769 mL | |
| 5 mM | 0.4975 mL | 2.4877 mL | 4.9754 mL | |
| 10 mM | 0.2488 mL | 1.2438 mL | 2.4877 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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