compound 5e [PMID: 28580438]   Click here for help

GtoPdb Ligand ID: 9712

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Compound 5e is a potent FMS-like tyrosine kinase 3 (FLT3, a type III receptor tyrosine kinase) inhibitor that is in preclinical evaluation for the treatment of acute myelogenous leukemia (AML) [3].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 5
Topological polar surface area 62.73
Molecular weight 305.16
XLogP 3.61
No. Lipinski's rules broken 0
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Canonical SMILES CC(Nc1ccnc(n1)Nc1cccc(c1)c1cccnc1)C
Isomeric SMILES CC(Nc1ccnc(n1)Nc1cccc(c1)c1cccnc1)C
InChI InChI=1S/C18H19N5/c1-13(2)21-17-8-10-20-18(23-17)22-16-7-3-5-14(11-16)15-6-4-9-19-12-15/h3-13H,1-2H3,(H2,20,21,22,23)
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Mechanism Of Action and Pharmacodynamic Effects Click here for help
FLT3 is required for the normal development and proliferation of hematopoietic stem cells via activation of the RAS, SRC, and STAT5 pathways [1-2,5]. However, constitutive activity of FLT3 (caused by mutation) is oncogenic [6], leading to uncontrolled hematopoietic stem cell proliferation, and this is found to be the causative mechanism in ~30% of cases of AML [4,7]. FLT3 inhibitors target this abnormal level of pathway activation to reduce hematopoietic stem cell proliferation.