Substituted 4-amino-1H-pyrazolo[3,4-d]pyrimidines as multi-targeted inhibitors of insulin-like growth factor-1 receptor (IGF1R) and members of ErbB-family receptor kinases.

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Wang GT, Mantei RA, Hubbard RD, Wilsbacher JL, Zhang Q, Tucker L, Hu X, Kovar P, Johnson EF, Osterling DJ, Bouska J, Wang J, Davidsen SK, Bell RL, Sheppard GS

Substituted 4-amino-1H-pyrazolo[3,4-d]pyrimidines as multi-targeted inhibitors of insulin-like growth factor-1 receptor (IGF1R) and members of ErbB-family receptor kinases.

Bioorg Med Chem Lett. 2010 Oct 15;20(20):6067-71. doi: 10.1016/j.bmcl.2010.08.052. Epub 2010 Aug 13.

PubMed ID

20817523 [ View in PubMed

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Abstract

This Letter describes the lead discovery, optimization, and biological characterization of a series of substituted 4-amino-1H-pyrazolo[3,4-d]pyrimidines as potent inhibitors of IGF1R, EGFR, and ErbB2. The leading compound 11 showed an IGF1R IC(50) of 12 nM, an EGFR (L858R) IC(50) of 31 nM, and an ErbB2 IC(50) of 11 nM, potent activity in cellular functional and anti-proliferation assays, as well as activity in an in vivo pharmacodynamic assay.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Erlotinib	Epidermal growth factor receptor	IC 50 (nM)	51	N/A	N/A	Details
Lapatinib	Epidermal growth factor receptor	IC 50 (nM)	433	N/A	N/A	Details
Lapatinib	Receptor tyrosine-protein kinase erbB-2	IC 50 (nM)	140	N/A	N/A	Details