PD 174265 

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^[1][2][3][4].

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.

PD 174265 (58 mg/kg; i.p.; on days 10-14, 17-21, and 24-28 after tumor implant) exhibits weak in vivo antitumor activity against A431 human epidermoid carcinoma xenografts in nude mice, with 13% tumor growth inhibition, and only transiently suppresses EGFR phosphotyrosine content^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

371.23

C₁₇H₁₅BrN₄O

216163-53-0

Solid

Light yellow to yellow

CCC(NC1=CC2=C(NC3=CC=CC(Br)=C3)N=CN=C2C=C1)=O

Room temperature in continental US; may vary elsewhere.

4°C, protect from light

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

* 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.

• [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]