DPH
(Synonyms: 5-(3-(4-氟苯基)-1-苯基-1H-吡唑-4-基)咪唑烷-2,4-二酮) 目录号 : GC35897
DPH是一种具有细胞渗透性的小分子c-Abl激酶激活剂。
Cas No.:484049-04-9
Sample solution is provided at 25 µL, 10mM.
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DPH is a cell-permeable, small-molecule activator of c-Abl kinase [1]. DPH binds to the myristoyl binding site and prevents the formation of the bent conformation of the αI helix through steric hindrance [2]. DPH has been widely used to affect the intracellular localization of c-Abl and regulate the progression of breast cancer cells[3].
In vitro, DPH treatment (50μM) with for 3 hours resulted in a significant increase in the phosphorylation levels of α-synuclein at the Y39 and Y125 sites in SH-SY5Y cells[4]. Treatment with 40μM DPH for 60 hours significantly inhibited the proliferation of MDA-MB-231 cells with TTK expression deficiency[5]. Treatment with 0.5μM DPH for 2 hours led to a significant increase in the proportion of mitochondria fragmentation in primary cortical neurons of mice, and also elevated the phosphorylation level of Drp1 at Ser616[6].
In vivo, DPH treatment via tail vein injection at a dose of 5μg/day for 30 consecutive days significantly reduced the neuronal apoptosis rate in the striatum and cerebellum of Hax1 gene knockout mice[7].
References:
[1] Simpson G L, Bertrand S M, Borthwick J A, et al. Identification and optimization of novel small c-Abl kinase activators using fragment and HTS methodologies[J]. Journal of medicinal chemistry, 2019, 62(4): 2154-2171.
[2] Yang J, Campobasso N, Biju M P, et al. Discovery and characterization of a cell-permeable, small-molecule c-Abl kinase activator that binds to the myristoyl binding site[J]. Chemistry & biology, 2011, 18(2): 177-186.
[3] Morrison C D, Gilmore H, Schiemann W P. Abstract P4-05-08: Cellular localization dictates the role for c-Abl in breast cancer[J]. Cancer Research, 2015, 75(9_Supplement): P4-05-08-P4-05-08.
[4] Mahul-Mellier A L, Fauvet B, Gysbers A, et al. c-Abl phosphorylates α-synuclein and regulates its degradation: implication for α-synuclein clearance and contribution to the pathogenesis of Parkinson's disease[J]. Human molecular genetics, 2014, 23(11): 2858-2879.
[5] Morrison C D, Chang J C, Keri R A, et al. Mutant p53 dictates the oncogenic activity of c-Abl in triple-negative breast cancers[J]. Cell death & disease, 2017, 8(6): e2899-e2899.
[6] Zhou L, Zhang Q, Zhang P, et al. c-Abl-mediated Drp1 phosphorylation promotes oxidative stress-induced mitochondrial fragmentation and neuronal cell death[J]. Cell death & disease, 2017, 8(10): e3117-e3117.
[7] Dong Q, Li D, Zhao H, et al. Anti-apoptotic HAX-1 suppresses cell apoptosis by promoting c-Abl kinase-involved ROS clearance[J]. Cell Death & Disease, 2022, 13(4): 298.
DPH是一种具有细胞渗透性的小分子c-Abl激酶激活剂[1]。DPH结合在豆蔻酰基结合位点，并通过空间位阻阻止αI螺旋形成弯曲构象[2]。DPH已广泛应用于影响c-Abl的细胞内定位并调节乳腺癌细胞的进展[3]。
在体外，DPH处理（50μM）3小时导致SH-SY5Y细胞中α-突触核蛋白Y39和Y125位点的磷酸化水平显著增加[4]。用40μM的DPH处理60小时显著抑制了TTK表达缺陷的MDA-MB-231细胞的增殖[5]。用0.5μM的DPH处理2小时导致小鼠原代皮质神经元中线粒体碎片化的比例显著增加，并提高了Drp1 Ser616位点的磷酸化水平[6]。
在体内，以5μg/day的剂量连续30天尾静脉注射DPH显著降低了Hax1基因敲除小鼠纹状体和小脑中的神经元凋亡率[7]。
| Cell experiment [1]: | |
Cell lines | MDA-MB-231 cells |
Preparation Method | MDA-MB-231 cells were cultured in DMEM medium containing 10% fetal bovine serum (FBS) for 48 hours. 1% of dual antibiotics were added to the medium and the cells were incubated at 37°C in a 5% CO2 environment. MDA-MB-231 cells (1000 cells per well) were seeded in 96-well plates and then treated with BV02 (1.0μM), MPS1-IN-3 (0.5μM), or DPH (40μM) for culture, which were used alone or in combination, and analyzed for cell proliferation after 60 hours. |
Reaction Conditions | 40μM; 60h |
Applications | The combined treatment of DPH and MPS1-IN-3/BV02 significantly inhibited the proliferation of MDA-MB-231 cells. |
| Animal experiment [2]: | |
Animal models | C57 Hax-1−/+ mice |
Preparation Method | The C57 Hax-1−/+ mice were raised in a standard sterile environment and had free access to food and water. Before the experiment, 28-day-old wild-type (WT) or Hax-1−/+ mice female mice (8 mice per group) were randomly grouped. Then, mice were injected with DPH (5μg/day) or vehicle via the tail vein every day for 30 consecutive days. After the mice were sacrificed, and were immediately perfused with 4% paraformaldehyde for fixation. The striatum and cerebellum were then removed for analysis. |
Dosage form | 5μg/day for 30 days; tail vein injection |
Applications | DPH significantly reduced the neuronal apoptosis rate in the striatum and cerebellum of Hax-1−/+ mice. |
References: | |
| Cas No. | 484049-04-9 | SDF | |
| 别名 | 5-(3-(4-氟苯基)-1-苯基-1H-吡唑-4-基)咪唑烷-2,4-二酮 | ||
| Canonical SMILES | O=C1NC(C(N1)C2=CN(N=C2C3=CC=C(C=C3)F)C4=CC=CC=C4)=O | ||
| 分子式 | C18H13FN4O2 | 分子量 | 336.32 |
| 溶解度 | DMSO: 100 mg/mL (297.34 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.9734 mL | 14.8668 mL | 29.7336 mL |
| 5 mM | 594.7 μL | 2.9734 mL | 5.9467 mL |
| 10 mM | 297.3 μL | 1.4867 mL | 2.9734 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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计算结果:
工作液浓度： mg/ml；
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2.
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Quality Control & SDS
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- Purity: >98.00%
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