compound 7d [PMID: 29672049]

Ligand id: 9937

Name: compound 7d [PMID: 29672049]

Structure and Physico-chemical Properties

2D Structure
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Calculated 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

Molecular properties generated using the CDK

Bioactivity Comments
Compound 7d inhibits activity of the oncogenic FLT3-internal tandem duplications (ITD) mutant kinase with an IC50 of 3 nM in a biochemical assay [1]. Potent inhibition of the FLT3D835Y point mutation is observed, with an IC50 of 8 nM (similar to the wild type IC50 of 13 nM). It inhibits proliferation of AML cells carrying FLT3-ITD mutations (MV4-11 cells; GI50 2 nM), and FLT3-ITD positive MOLM-13 cells (GI50 1 nM). The inhibition of MV4-11 cell proliferation is replicated in vivo, in xenografts grown in immunocompromised mice. Compound 7d also inhibits proliferation of K562 cells which don't have the FLT3-ITD mutation, although with a much lower efficacy (GI50 380 nM) [1]. In a selectivity screening panel of 309 kinases, 10 nM compound 7d inhibited several other kinases by > 90% (including PDGFRα/β, CLK1, TRK, QIK, CaMK2δ, SIK, YES, FMS, CAMK2γ, KITD816V, MNK2, ACK, and Src).
Selectivity at catalytic receptors
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
fms related receptor tyrosine kinase 3 Hs Inhibitor Inhibition 7.9 pIC50 - 1
pIC50 7.9 (IC50 1.3x10-8 M) [1]
Description: In a biochemical assay.