3-Phenyl-1H-5-pyrazolylamine-based derivatives as potent and efficacious inhibitors of FMS-like tyrosine kinase-3 (FLT3).

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Hsu JT, Yeh TK, Yen SC, Chen CT, Hsieh SY, Hsu T, Lu CT, Chen CH, Chou LH, Chiu CH, Chang YI, Tseng YJ, Yen KR, Chao YS, Lin WH, Jiaang WT

3-Phenyl-1H-5-pyrazolylamine-based derivatives as potent and efficacious inhibitors of FMS-like tyrosine kinase-3 (FLT3).

Bioorg Med Chem Lett. 2012 Jul 15;22(14):4654-9. doi: 10.1016/j.bmcl.2012.05.116. Epub 2012 Jun 7.

PubMed ID

22726931 [ View in PubMed

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Abstract

A new class of FLT3 inhibitors has been identified based on the 3-phenyl-1H-5-pyrazolylamine scaffold. The structure-activity relationships led to the discovery of two carbamate series, and some potent compounds within these two series exhibited better growth inhibition of FLT3-mutated MOLM-13 cells than FLT3 inhibitors sorafenib (2) and ABT-869 (3). In particular, compound 8d exhibited the ability to regress tumors in mouse xenograft model using MOLM-13 cells.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Sorafenib	Receptor-type tyrosine-protein kinase FLT3	IC 50 (nM)	54	N/A	N/A	Details
Sorafenib	Vascular endothelial growth factor receptor 1	IC 50 (nM)	165	N/A	N/A	Details
Sorafenib	Vascular endothelial growth factor receptor 2	IC 50 (nM)	20	N/A	N/A	Details