compound 7d [PMID: 29672049]   

GtoPdb Ligand ID: 9937

Compound class: Synthetic organic
Comment: Compound 7d is a FLT3 inhibitor [1]. It was identified as a lead compound in a medicinal chemistry study to find novel chemical scaffolds that offer improved FLT3 inhibition, and that provide compounds with potential clinical oncology therapeutic value for FLT3-driven cancers. Similar levels of inhibition of wild type and D835Y-mutated FLT3 enzymes suggests that compound 7d is a Type I (ATP binding site) kinase inhibitor. In comparison to quizartinib, a single dose of compound 7d produces a longer-lived inhibition of FLT3 and STAT5 phosphorylation in xenograft mice.
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 8
Hydrogen bond donors 3
Rotatable bonds 7
Topological polar surface area 106.15
Molecular weight 490.32
XLogP 3.5
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES NC1CCC(CC1)Nc1nc(Nc2ccc(cc2)CN2CCOCC2)c2c(n1)n(cn2)C1CCCC1
Isomeric SMILES N[C@@H]1CC[C@H](CC1)Nc1nc(Nc2ccc(cc2)CN2CCOCC2)c2c(n1)n(cn2)C1CCCC1
InChI InChI=1S/C27H38N8O/c28-20-7-11-22(12-8-20)31-27-32-25(24-26(33-27)35(18-29-24)23-3-1-2-4-23)30-21-9-5-19(6-10-21)17-34-13-15-36-16-14-34/h5-6,9-10,18,20,22-23H,1-4,7-8,11-17,28H2,(H2,30,31,32,33)/t20-,22-
InChI Key SAEGVASGMTZGFI-AQYVVDRMSA-N
No information available.
Mechanism Of Action and Pharmacodynamic Effects
Compound 7d inhibits FLT3 autophosphorylation and down modulates its downstream signaling pathways. This action ultimately leads to cell cycle arrest and apoptosis of FLT3-ITD positive MV4-11 cells.