6LVL

Crystal structure of FGFR2 in complex with 1,3,5-triazine derivative

Summary for 6LVL

• Entry DOI: 10.2210/pdb6lvl/pdb
• Related: 6LVK
• Descriptor: Fibroblast growth factor receptor 2, SULFATE ION, N-ethyl-2-[[4-[[3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]amino]-1,3,5-triazin-2-yl]amino]benzenesulfonamide (3 entities in total)
• Functional Keywords: protein kinase, signaling protein, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 73160.19

Authors

Echizen, Y.,Tateishi, Y.,Amano, Y. (deposition date: 2020-02-04, release date: 2020-04-08, Last modification date: 2023-11-29)

Primary citation

Kuriwaki, I.,Kameda, M.,Hisamichi, H.,Kikuchi, S.,Iikubo, K.,Kawamoto, Y.,Moritomo, H.,Kondoh, Y.,Amano, Y.,Tateishi, Y.,Echizen, Y.,Iwai, Y.,Noda, A.,Tomiyama, H.,Suzuki, T.,Hirano, M.
Structure-based drug design of 1,3,5-triazine and pyrimidine derivatives as novel FGFR3 inhibitors with high selectivity over VEGFR2.
Bioorg.Med.Chem., 28:115453-115453, 2020

PubMed Abstract: Fibroblast growth factor receptor 3 (FGFR3) is an attractive therapeutic target for the treatment of bladder cancer. We identified 1,3,5-triazine derivative 18b and pyrimidine derivative 40a as novel structures with potent and highly selective FGFR3 inhibitory activity over vascular endothelial growth factor receptor 2 (VEGFR2) using a structure-based drug design (SBDD) approach. X-ray crystal structure analysis suggests that interactions between 18b and amino acid residues located in the solvent region (Lys476 and Met488), and between 40a and Met529 located in the back pocket of FGFR3 may underlie the potent FGFR3 inhibitory activity and high kinase selectivity over VEGFR2.

PubMed: 32278710
DOI: 10.1016/j.bmc.2020.115453

Experimental method

X-RAY DIFFRACTION (2.98 Å)