| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
PU.1 transcription factor.
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|---|---|
| ln Vitro |
Treatment with DB2313 significantly inhibited the proliferation of PU.1 URE–/– acute myeloid leukemia (AML) cells (IC50 of 7.1 μM), but at identical concentrations, had no effect on normal hematopoietic cells. In mouse PU.1 URE–/– AML cells, DB2313 therapy led to a 3.5-fold increase in apoptotic cells. Additionally, in the second and third rounds of plating, DB2313 significantly reduces clonogenicity; in the fourth and succeeding rounds, clonogenicity is completely disrupted [1]. PU.1 occupancy on the E2f1, Junb, and Csf1r promoters is decreased in AML cells by DB2313 [1].
DB2313 inhibits PU.1-dependent reporter gene transactivation with an IC50 of 5 μM. It reduces PU.1 occupancy at the E2f1, Junb, and Csf1r promoters in AML cells. By inhibiting PU.1, it induces apoptosis in AML cells and has anticancer effects. |
| ln Vivo |
Mice treated with DB2313 (17 mg/kg; intraperitoneal injection; three times per week; for three weeks) had enhanced survival and delayed the course of leukemia [1].
In vivo, DB2313 increases survival rates and reduces tumor burden in AML models. It has been shown to have significant anti-leukemic activity. It is a promising candidate for the treatment of AML and other PU.1-driven cancers. |
| Enzyme Assay |
DB2313 is evaluated in cell-free assays for PU.1 DNA binding. Electrophoretic mobility shift assays (EMSA) or fluorescence polarization assays are performed to assess the inhibition of PU.1 binding to its DNA response element. The compound is incubated with PU.1 protein and a labeled DNA probe, and the inhibition of complex formation is measured.
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| Cell Assay |
DB2313 is assessed in cell-based assays using AML cell lines. Cells are treated with DB2313, and PU.1 activity is measured by assessing reporter gene expression or target gene expression. Apoptosis is measured using flow cytometry or caspase activity assays. Cell viability and proliferation are also assessed.
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| Animal Protocol |
Animal/Disease Models: NSG mice receiving sublethal radiation (2.0 Gy) and injected with PU.1 URE–/– AML cells [1]
Doses: 17 mg/kg Route of Administration: intraperitoneal (ip) injection; three times per week; for 3 weeks Experimental Results: Tumor burden diminished and resulted in increased survival. DB2313 is administered in animal models of AML to evaluate its anti-leukemic efficacy. Efficacy is assessed by measuring tumor burden, survival rates, and apoptosis in tumor tissues. Pharmacokinetic studies are conducted to assess bioavailability and tissue distribution. |
| ADME/Pharmacokinetics |
No detailed PK data available. DB2313 has a molecular weight of 708.83. Soluble in DMSO (10 mg/mL). Purity ≥98%.
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| Toxicity/Toxicokinetics |
No detailed toxicity data available. For research use only.
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| References |
[1]. Iléana Antony-Debré, et al. Pharmacological inhibition of the transcription factor PU.1 in leukemia. J Clin Invest. 2017 Dec 1;127(12):4297-4313.
[2]. Zhang S, Zhao S, Qi Y, et al. SPI1-induced downregulation of FTO promotes GBM progression by regulating pri-miR-10a processing in an m6A-dependent manner. Mol Ther Nucleic Acids. 2022;27:699-717. |
| Additional Infomation |
DB2313 is a potent PU.1 inhibitor. Molecular formula: C42H41FN8O2; MW: 708.83. Induces apoptosis in AML cells. For research use only.
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| Molecular Formula |
C42H41FN8O2
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|---|---|
| Molecular Weight |
708.825752019882
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| Exact Mass |
708.333
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| CAS # |
2170606-74-1
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| PubChem CID |
138556040
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
6.9
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
53
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| Complexity |
1130
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)N=C(C1=CC2=C(C=C1)N=C(N2)C3=CC=C(C=C3)OCC4=C(C(=CC=C4)COC5=CC=C(C=C5)C6=NC7=C(N6)C=C(C=C7)C(=NC(C)C)N)F)N
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| InChi Key |
NUVPJXUYFGWDGB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C42H41FN8O2/c1-24(2)46-39(44)28-12-18-34-36(20-28)50-41(48-34)26-8-14-32(15-9-26)52-22-30-6-5-7-31(38(30)43)23-53-33-16-10-27(11-17-33)42-49-35-19-13-29(21-37(35)51-42)40(45)47-25(3)4/h5-21,24-25H,22-23H2,1-4H3,(H2,44,46)(H2,45,47)(H,48,50)(H,49,51)
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| Chemical Name |
2-[4-[[2-fluoro-3-[[4-[6-(N'-propan-2-ylcarbamimidoyl)-1H-benzimidazol-2-yl]phenoxy]methyl]phenyl]methoxy]phenyl]-N'-propan-2-yl-3H-benzimidazole-5-carboximidamide
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| Synonyms |
DB-2313; DB 2313; DB2313
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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 : ~3.7 mg/mL (~5.22 mM ()
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| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (7.05 mM) in 50% PEG300 +50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4108 mL | 7.0539 mL | 14.1078 mL | |
| 5 mM | 0.2822 mL | 1.4108 mL | 2.8216 mL | |
| 10 mM | 0.1411 mL | 0.7054 mL | 1.4108 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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