Novel inhibitors of epidermal growth factor receptor: (4-(Arylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl)(1H-indol-2-yl)methanones and (1H-indol-2-yl)(4-(phenylamino)thieno[2,3-d]pyrimidin-6-yl)methanones.

Article Details

Citation

Beckers T, Sellmer A, Eichhorn E, Pongratz H, Schachtele C, Totzke F, Kelter G, Krumbach R, Fiebig HH, Bohmer FD, Mahboobi S

Novel inhibitors of epidermal growth factor receptor: (4-(Arylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl)(1H-indol-2-yl)methanones and (1H-indol-2-yl)(4-(phenylamino)thieno[2,3-d]pyrimidin-6-yl)methanones.

Bioorg Med Chem. 2012 Jan 1;20(1):125-36. doi: 10.1016/j.bmc.2011.11.023. Epub 2011 Nov 20.

PubMed ID
22169601 [ View in PubMed
]
Abstract

Several members of the quinazoline class of known tyrosine kinase inhibitors are approved anticancer agents, often showing selectivity for receptors of the HER/ErbB-family. Combining structural elements of this class with the bisindolylmethanone-structure led to a series of novel compounds. These compounds inhibited EGFR in the nanomolar range. Moreover, inhibition of EGFR autophosphorylation in intact A431 cells was shown, with IC(50) values ranging form 0.3-1muM for compound 42, and 0.1-0.3muM for 45. In a panel of 42 human tumor cell lines the sensitivity profile of the novel compounds was shown to be similar to that of the quinazoline class of tyrosine kinase inhibitors lapatinib and erlotinib (Tarceva(R)).

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
ErlotinibEpidermal growth factor receptorIC 50 (nM)3.1N/AN/ADetails
LapatinibEpidermal growth factor receptorIC 50 (nM)8.9N/AN/ADetails
LapatinibReceptor tyrosine-protein kinase erbB-2IC 50 (nM)60N/AN/ADetails