DPH |
Catalog No.GC35897
One-Click Copy Product Info
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DPH is a cell-permeable, small-molecule activator of c-Abl kinase.
Products are for research use only. Not for human use. We do not sell to patients.
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.
| 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 | |
| Canonical SMILES | O=C1NC(C(N1)C2=CN(N=C2C3=CC=C(C=C3)F)C4=CC=CC=C4)=O | ||
| Formula | C18H13FN4O2 | M.Wt | 336.32 |
| Solubility | DMSO: 100 mg/mL (297.34 mM) | 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. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 22 reference(s) in Google Scholar.)