| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
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DB1976 (DB-1976), a selenophene analog of DB270, is a novel and potent transcription factor PU.1 inhibitor with apoptosis-inducing activity. It inhibits PU.1 binding (IC50 = 10 nM) and strongly inhibits the PU.1/DNA complex (with high DB1976-λB affinity, KD = 12 nM).
| ln Vitro |
DB1976 is a traditional heterocyclic dilabel, or single heteroatom, that exhibits high selectivity and affinity for AT-rich sequences that are frequently present in PU.1's homologous DNA binding site. When applied to PU.1-negative HEK293 cells, DB1976 has an IC50 value of 2.4 μM and suppresses PU.1-dependent reporter gene transactivation in a dose-dependent manner [3]. Treatment with DB1976 significantly inhibited the development of PU.1 URE–/– AML cells (IC50 of 105 μM), but had no effect on normal hematopoietic cells (IC50 of 334 μM) at identical dosages [3]. In mouse PU.1 URE–/– AML cells, DB1976 administration led to a 1.6-fold increase in apoptotic cells; same effects were noted in human MOLM13 cells [3]. When compared to cells treated with a vehicle, DB1976 treatment significantly decreased the number of viable cells (primary human AML cells) (mean reduction of 81%) and the clonogenic capability (mean reduction of 36%). The apoptotic cell fraction is increased by DB1976 by an average of 1.5 times [3].
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| References |
[1]. Munde M, et al. Structure-dependent inhibition of the ETS-family transcription factor PU.1 by novel heterocyclic diamidines. Nucleic Acids Res. 2014 Jan;42(2):1379-90.
[2]. Stephens DC, et al. Pharmacologic efficacy of PU.1 inhibition by heterocyclic dications: a mechanistic analysis. Nucleic Acids Res. 2016 May 19;44(9):4005-13. [3]. Antony-Debré I, et al. Pharmacological inhibition of the transcription factor PU.1 in leukemia. J Clin Invest. 2017 Dec 1;127(12):4297-4313. |
| Molecular Formula |
C20H16N8SE
|
|---|---|
| Molecular Weight |
447.354640960693
|
| Exact Mass |
448.066
|
| CAS # |
1557397-51-9
|
| Related CAS # |
DB1976 dihydrochloride;2369663-93-2
|
| PubChem CID |
141655595
|
| Appearance |
Typically exists as solid at room temperature
|
| Hydrogen Bond Donor Count |
6
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
29
|
| Complexity |
604
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
NXECULIQZLOKFU-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C20H16N8Se/c21-17(22)9-1-3-11-13(7-9)27-19(25-11)15-5-6-16(29-15)20-26-12-4-2-10(18(23)24)8-14(12)28-20/h1-8H,(H3,21,22)(H3,23,24)(H,25,27)(H,26,28)
|
| Chemical Name |
2-[5-(6-carbamimidoyl-1H-benzimidazol-2-yl)selenophen-2-yl]-3H-benzimidazole-5-carboximidamide
|
| Synonyms |
DB-1976 DB 1976
|
| 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 | 2.2354 mL | 11.1769 mL | 22.3539 mL | |
| 5 mM | 0.4471 mL | 2.2354 mL | 4.4708 mL | |
| 10 mM | 0.2235 mL | 1.1177 mL | 2.2354 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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