PD 174265
Based on 1 Customer Validation
PD 174265 is a highly selective, reversible EGFR/ErbB2 tyrosine kinase inhibitor (IC50=0.45 nM) and cell differentiation inducer. By blocking receptor autophosphorylation and the downstream ERK signaling pathway (with an IC50 of 0.45 μM for full-length ERK), PD 174265 effectively inhibits tumor growth and exhibits antitumor activity without obvious toxicity in in vivo models. PD 174265 drives oligodendrocyte precursor cells to switch from a proliferative state to a differentiated state, significantly upregulates the expression of myelin proteins such as CNP, PLP and MBP, and induces neurite branching. PD 174265 shows no inhibitory effect on other kinases including insulin, PDGF and basic FGF receptors, and serves as a crucial tool molecule for investigating the treatment of human epidermoid carcinoma and the mechanism of myelin repair in multiple sclerosis.
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- Pureza : 98.35%
- No. CAS: 216163-53-0
- Fòrmula: C17H15BrN4O
- Peso molecular:371.23
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Almacenamiento:
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Protocolo
- Pureza y Documentación
- Referencias
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Help & FAQs
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Actividad biológica
Descripciòn
IC50 & Target
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ErbB2 |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A-431 | GI50 |
0.021 μM
Compound: PD-168393
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Growth inhibition of human A431 cells after 72 hrs by MTT assay
Growth inhibition of human A431 cells after 72 hrs by MTT assay
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[PMID: 19969465] |
| BaF3 | GI50 |
<0.5 μM
Compound: 3d
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Growth inhibition of mouse BA/F3 cells expressing EGFR Del1 mutant after 96 hrs by cell titer-glo assay
Growth inhibition of mouse BA/F3 cells expressing EGFR Del1 mutant after 96 hrs by cell titer-glo assay
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[PMID: 20222733] |
| BaF3 | GI50 |
<0.5 μM
Compound: 3d
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Growth inhibition of mouse BA/F3 cells expressing EGFR Del3 mutant after 96 hrs by cell titer-glo assay
Growth inhibition of mouse BA/F3 cells expressing EGFR Del3 mutant after 96 hrs by cell titer-glo assay
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[PMID: 20222733] |
| BaF3 | GI50 |
<0.5 μM
Compound: 3d
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Growth inhibition of mouse BA/F3 cells expressing EGFR Del5 mutant after 96 hrs by cell titer-glo assay
Growth inhibition of mouse BA/F3 cells expressing EGFR Del5 mutant after 96 hrs by cell titer-glo assay
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[PMID: 20222733] |
| BaF3 | GI50 |
<0.5 μM
Compound: 3d
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Growth inhibition of mouse BA/F3 cells expressing EGFR L858R mutant after 96 hrs by cell titer-glo assay
Growth inhibition of mouse BA/F3 cells expressing EGFR L858R mutant after 96 hrs by cell titer-glo assay
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[PMID: 20222733] |
| BaF3 | GI50 |
>0.5 μM
Compound: 3d
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Growth inhibition of mouse BA/F3 cells expressing EGFR Del3 and Thr790Met mutant after 96 hrs by cell titer-glo assay
Growth inhibition of mouse BA/F3 cells expressing EGFR Del3 and Thr790Met mutant after 96 hrs by cell titer-glo assay
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[PMID: 20222733] |
| BaF3 | GI50 |
>5 μM
Compound: 3d
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Growth inhibition of mouse BA/F3 cells expressing EGFR Del1 and Thr790Met mutant after 96 hrs by cell titer-glo assay
Growth inhibition of mouse BA/F3 cells expressing EGFR Del1 and Thr790Met mutant after 96 hrs by cell titer-glo assay
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[PMID: 20222733] |
| BaF3 | GI50 |
>5 μM
Compound: 3d
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Growth inhibition of mouse BA/F3 cells expressing EGFR Del5 and Thr790Met mutant after 96 hrs by cell titer-glo assay
Growth inhibition of mouse BA/F3 cells expressing EGFR Del5 and Thr790Met mutant after 96 hrs by cell titer-glo assay
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[PMID: 20222733] |
| BaF3 | GI50 |
>5 μM
Compound: 3d
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Growth inhibition of mouse BA/F3 cells expressing EGFR L858R and Thr790Met mutant after 96 hrs by cell titer-glo assay
Growth inhibition of mouse BA/F3 cells expressing EGFR L858R and Thr790Met mutant after 96 hrs by cell titer-glo assay
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[PMID: 20222733] |
In Vitro
PD 174265 (1-10 μM; 72 h, 3 days) induces the differentiation of Oli-neu mouse oligodendrocyte precursor cells, which is characterized by increased axonal growth and upregulated expression of myelin-related markers CNP, PLP and MBP; specifically, when treated with 1 μM for 72 h, the induced expression level of MBP mRNA reaches approximately 8 times that of the control group, representing the maximum value[1].
PD 174265 (1 μM; 3 d) induces differentiation of primary rat oligodendrocyte precursor cells, as evidenced by increased mRNA and protein levels of myelin markers CNP, MBP and PLP following 3 days of treatment with 1 μM[1].
PD 174265 (2 μM; 1 h) reversibly inhibits EGF-dependent EGFr autophosphorylation in A431 human epidermoid carcinoma cells, and the activity recovers completely after 8 hr of culture in medium without this compound[2].
PD 174265 reversibly inhibits EGF-induced EGFR autophosphorylation in A431 human epidermal cancer cells (IC50=39 nM), as well as heregulin-induced erbB2 autophosphorylation in MDA-MB-453 human breast cancer cells (IC50=220 nM)[2].
PD 174265 (following 4 h of EGF/TGF pretreatment and under variable co-incubation conditions) reverses the EGF- and TGF-induced increase in PS-ASO activity in A431 cells by blocking the phosphorylation of EGFR and ERK, restoring the IC50 value of PS-ASO to the level of the control group[3].
PD 174265 (1 μM; 10 min preincubation) causes a non-specific false-positive increase in mitochondrial ROS production in adult rabbit ventricular myocytes, with a level comparable to that induced by acetylcholine[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Oli-neu mouse oligodendrocyte precursor cell
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Concentration:1-10 μM (screening); 1 μM (morphological analysis and Western blotting); serial dilutions (dose-response curve)
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Incubation Time:72 h (screening); 3 days (morphological analysis, Western blotting, dose-response curve)
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Result:Induced dose-dependent Oli-neu differentiation, with extensive cellular branching at optimal concentrations. Stimulated time-dependent upregulation of CNP, PLP, and MBP mRNA: by 72 h, MBP mRNA reached ~8-fold over control, CNP mRNA reached ~4-fold over control, and PLP mRNA reached ~4-fold over control. Induced time-dependent increases in CNP and MBP protein, with peak expression at 3 days of treatment. Produced a sigmoidal dose-response curve for the neurite outgrowth index, with activity increasing at concentrations above 0.1 μM.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Athymic nude mice with Epidermoid carcinoma[2]
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Dosage:58 mg/kg (antitumor activity); 58 mg/kg (EGFr phosphotyrosine analysis)
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Administration:i.p.; on days 10-14, 17-21, and 24-28 after tumor implant (antitumor activity); single dose (EGFr phosphotyrosine analysis)
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Result:Produced a tumor growth inhibition of 13%. Reduced EGFr phosphotyrosine content by ~80% at 4 hours post-injection. Returned EGFr phosphotyrosine content to ~75% of control levels by 8 hours post-injection. Restored EGFr phosphotyrosine content to 100% of control levels by 24 hours post-injection.
Chemical Information
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No. CAS 216163-53-0
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Appearance Solid
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Peso molecular 371.23
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Fòrmula C17H15BrN4O
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Color Light yellow to yellow
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SMILES
CCC(NC1=CC2=C(NC3=CC=CC(Br)=C3)N=CN=C2C=C1)=O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
Solvente y solubilidad
In Vitro:
DMSO : 125 mg/mL (336.72 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Pureza y Documentación
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Ficha de datos (279 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[1]. Joubert L, et al. Chemical inducers and transcriptional markers of oligodendrocyte differentiation. J Neurosci Res. 2010;88(12):2546-2557. [Content Brief]
[2]. Fry DW, et al. Specific, irreversible inactivation of the epidermal growth factor receptor and erbB2, by a new class of tyrosine kinase inhibitor. Proc Natl Acad Sci U S A. 1998;95(20):12022-12027. [Content Brief]
[3]. Wang S, et al. Cellular uptake mediated by epidermal growth factor receptor facilitates the intracellular activity of phosphorothioate-modified antisense oligonucleotides. Nucleic Acids Res. 2018;46(7):3579-3594. [Content Brief]
[4]. Krieg T, et al. Mitochondrial ROS generation following acetylcholine-induced EGF receptor transactivation requires metalloproteinase cleavage of proHB-EGF. J Mol Cell Cardiol. 2004;36(3):435-443. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.6937 mL | 13.4687 mL | 26.9375 mL | 67.3437 mL |
| 5 mM | 0.5387 mL | 2.6937 mL | 5.3875 mL | 13.4687 mL | |
| 10 mM | 0.2694 mL | 1.3469 mL | 2.6937 mL | 6.7344 mL | |
| 15 mM | 0.1796 mL | 0.8979 mL | 1.7958 mL | 4.4896 mL | |
| 20 mM | 0.1347 mL | 0.6734 mL | 1.3469 mL | 3.3672 mL | |
| 25 mM | 0.1077 mL | 0.5387 mL | 1.0775 mL | 2.6937 mL | |
| 30 mM | 0.0898 mL | 0.4490 mL | 0.8979 mL | 2.2448 mL | |
| 40 mM | 0.0673 mL | 0.3367 mL | 0.6734 mL | 1.6836 mL | |
| 50 mM | 0.0539 mL | 0.2694 mL | 0.5387 mL | 1.3469 mL | |
| 60 mM | 0.0449 mL | 0.2245 mL | 0.4490 mL | 1.1224 mL | |
| 80 mM | 0.0337 mL | 0.1684 mL | 0.3367 mL | 0.8418 mL | |
| 100 mM | 0.0269 mL | 0.1347 mL | 0.2694 mL | 0.6734 mL |
PD 174265 Related Classifications
HY-112411 Related Classifications
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