PD168393

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Chemical Structure| 194423-15-9 同义名 : -
CAS号 : 194423-15-9
货号 : A137778
分子式 : C17H13BrN4O
纯度 : 99%+
分子量 : 369.22
MDL号 : MFCD02179207
存储条件：

Pure form Sealed in dry, room temperature

In solvent -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：
生物活性
靶点

  • EGFR/ErbB1

    EGFR, IC50:0.70 nM

  • EGFR/ErbB1

    EGFR, IC50:0.70 nM

  • EGFR/ErbB1

    EGFR, IC50:0.70 nM
描述 Many of the tyrosine kinase enzymes which are early components of the growth signal transduction pathway in mammalian cells are encoded by proto-oncogenes, and their transformation or overexpression has been shown to occur in a large percentage of clinical cancers. The epidermal growth factor receptor (EGFR), one of the tyrosine kinase enzymes, has thus become important target for cancer therapy [3]. PD168393 selectively targets and irreversibly inactivates the EGFR TK (tyrosine kinase) with IC50 value of 0.70 nM. PD168393 completely suppressed EGF-dependent receptor autophosphorylation in A431 cells during continuous exposure to 2 μM this compound for 1 hr [4]. Treatment of 3T3-Her2 cells with PD168393 showed rapid and potent inhibition of Her2-induced tyrosine phosphorylation with half-maximal inhibition at ≈100 nM and substantial inhibition at 10 min after drug addition [5]. In nude mice bearing A431 human epidermoid carcinoma as a xenograft, PD 168393 produced tumor growth inhibition of 115% with 58 mg/kg i.p. dosing [4].
作用机制 PD168393 inactivates the EGFR TK through specific, covalent modification of a cysteine residue present in the ATP binding pocket .
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.71mL

0.54mL

0.27mL

13.54mL

2.71mL

1.35mL

27.08mL

5.42mL

2.71mL
参考文献

[1]Bose R, Molina H, et al. Phosphoproteomic analysis of Her2/neu signaling and inhibition. Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):9773-8.

[2]David W. F, Alexander J. B, 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 Sep 29; 95(20): 12022–12027.

[3]Bridges AJ, Zhou H, Cody DR, Rewcastle GW, McMichael A, Showalter HD, Fry DW, Kraker AJ, Denny WA. Tyrosine kinase inhibitors. 8. An unusually steep structure-activity relationship for analogues of 4-(3-bromoanilino)-6,7-dimethoxyquinazoline (PD 153035), a potent inhibitor of the epidermal growth factor receptor. J Med Chem. 1996 Jan 5;39(1):267-76. doi: 10.1021/jm9503613. PMID: 8568816.

[4]Fry DW, Bridges AJ, Denny WA, Doherty A, Greis KD, Hicks JL, Hook KE, Keller PR, Leopold WR, Loo JA, McNamara DJ, Nelson JM, Sherwood V, Smaill JB, Trumpp-Kallmeyer S, Dobrusin EM. 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 Sep 29;95(20):12022-7. doi: 10.1073/pnas.95.20.12022. PMID: 9751783; PMCID: PMC21758.

[5]Bose R, Molina H, Patterson AS, Bitok JK, Periaswamy B, Bader JS, Pandey A, Cole PA. Phosphoproteomic analysis of Her2/neu signaling and inhibition. Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):9773-8. doi: 10.1073/pnas.0603948103. Epub 2006 Jun 19. PMID: 16785428; PMCID: PMC1502529.