DB1976 hydrochloride |
| رقم الكتالوجGC39628 |
هيدروكلوريد DB1769 هو نظير سيلينوفين لـ DB270 ومثبط عامل النسخ PU.1 الفعال والقابل للنفاذ للخلايا. هيدروكلوريد DB1769 يمنع ارتباط PU.1 بقوة (IC50 من 10 نانومتر) ويثبط بشدة مركب PU.1 / DNA (مع تقارب DB1769-&Lambda ؛ B ، KD من 12 نانومتر) في المختبر. هيدروكلوريد DB1769 له تأثير محفز للاستماتة.
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Cas No.: 2369663-93-2
Sample solution is provided at 25 µL, 10mM.
DB1976 hydrochloride is a efficacious transcription factor PU.1 inhibitor. DB1976 dihydrochloride potently inhibits PU.1 binding (IC50 of 10 nM) and strongly inhibits the PU.1/DNA complex (with high DB1976-λB affinity, KD of 12 nM) in vitro. DB1976 dihydrochloride has apoptosis-inducing effect[1] [4].
DB1976 hydrochloride(0.1-100 mM，48h) led to decrease in the growth of PU.1 URE–/– AML cells (IC50: 105 μM); After DB1976(25uM,24h) treatment, PU.1 was lentivirally expressed in MOLM13 cells, and it was observed that the cytotoxic effects of the compound were rescued and cell viability was increased after treatment with DB1976[1].
DB1976 hydrochloride (5 mg/kg/day,28days)exposure decreased the interstitial, sub-epicardial and perivascular fibrosis induced by Ang-II in the atrial tissue[2]. DB1976 (5 mg/kg/day,28days)effectively attenuated Ang-II-induced increase in the number of atrial fibroblasts and reduced the expression of PCNA, α-SMA, SMemb, ED-A fibronectin, and DDR2 in vitro and in vivo[2]. In an asthma model, DB1976 (1 mg/kg and 2.5 mg/kg，5 days per week for 3 weeks) increased airway eosinophils and reduced small airway collagen deposition but had no effect on the number of mucus-secreting cells[3].
References:
[1]. 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.
[2]. Hu J, et al. PU.1 inhibition attenuates atrial fibrosis and atrial fibrillation vulnerability induced by angiotensin-II by reducing TGF-β1/Smads pathway activation. J Cell Mol Med. 2021 Jul;25(14):6746-6759.
[3]. Tu, X., Gomez, H.M., Kim, R.Y. et al. Airway and parenchyma transcriptomics in a house dust mite model of experimental asthma. Respir Res 24, 32 (2023).
[4].Stephens DC, Kim HM, Kumar A, Farahat AA, Boykin DW, Poon GM. Pharmacologic efficacy of PU.1 inhibition by heterocyclic dications: a mechanistic analysis. Nucleic Acids Res. 2016 May 19;44(9):4005-13.
| Cell experiment [1]: | |
Cell lines | URE–/–AML cells；HEK293 cells. |
Preparation Method | PU.1 URE+/–Msh2–/– cells were treated with DB1976(0.1-100mM) for 48 hours. HEK293 cells were treated with DB1976(25μM) for 24 hours. |
Reaction Conditions | PU.1 URE–/–AML cells: (0.1-100) mM,48h;PU.1-negative HEK293 cells:25 μM,24h. |
Applications | The IC50 value of DB1976 dihydrochloride in PU.1-negative HEK293 cells is 2.4 μM；DB1976 dihydrochloride treatment significantly inhibited the growth of PU.1 URE-/-AML cells (IC50 of 105 μM), whereas it had less effect on normal hematopoietic cells (IC50 of 334 μM). |
| Animal experiment [2]: | |
Animal models | PU.1 Inhibition Model |
Preparation Method | C57BL/6 mice were administered with Ang-II+ DB 1976 (5 mg/day/kg) by intraperitoneal injection once a day for 28 days. |
Dosage form | 5 mg/day/kg；28 days；ip. |
Applications | DB1976 exposure decreased the interstitial, sub-epicardial and perivascular fibrosis induced by Ang-II in the atrial tissue. |
References: [1].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 [2].Hu J, et al. PU.1 inhibition attenuates atrial fibrosis and atrial fibrillation vulnerability induced by angiotensin-II by reducing TGF-β1/Smads pathway activation. J Cell Mol Med. 2021 Jul;25(14):6746-6759.. | |
| Cas No. | 2369663-93-2 | SDF | |
| Canonical SMILES | N=C(C1=CC=C2N=C(C3=CC=C(C4=NC5=CC=C(C(N)=N)C=C5N4)[Se]3)NC2=C1)N.[H]Cl.[H]Cl | ||
| Formula | C20H18Cl2N8Se | M.Wt | 520.28 |
| الذوبان | DMSO : 62.5 mg/mL (120.13 mM; Need ultrason); H20 : 18.33 mg/mL (35.23 mM; Need ultrasonic） | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.922 mL | 9.6102 mL | 19.2204 mL |
| 5 mM | 0.3844 mL | 1.922 mL | 3.8441 mL |
| 10 mM | 0.1922 mL | 0.961 mL | 1.922 mL |
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Average Rating: 5 (Based on Reviews and 22 reference(s) in Google Scholar.)
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