BLZ945   Click here for help

GtoPdb Ligand ID: 8250

Synonyms: BLZ 945 | BLZ-945
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: BLZ945 is reported as an orally active, potent and selective inhibitor of colony stimulating factor 1 receptor (CSF1R) [4]. It is also brain-penetrant. The compound was designed to deplete pro-tumorigenic tumour-associated macrophages (TAMs) in the tumour microenvironment [4], and has also been reported to inhibit osteoclast CSF1R activity which reduces skeletal related events in metastatic disease [3].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 3
Rotatable bonds 6
Topological polar surface area 124.61
Molecular weight 398.14
XLogP 2.32
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES CNC(=O)c1nccc(c1)Oc1ccc2c(c1)sc(n2)NC1CCCCC1O
Isomeric SMILES CNC(=O)c1nccc(c1)Oc1ccc2c(c1)sc(n2)N[C@@H]1CCCC[C@H]1O
InChI InChI=1S/C20H22N4O3S/c1-21-19(26)16-10-13(8-9-22-16)27-12-6-7-15-18(11-12)28-20(24-15)23-14-4-2-3-5-17(14)25/h6-11,14,17,25H,2-5H2,1H3,(H,21,26)(H,23,24)/t14-,17-/m1/s1
InChI Key ADZBMFGQQWPHMJ-RHSMWYFYSA-N
Bioactivity Comments
In a kinase panel screen only three interactions with this compound were identified, CSF1R, cKIT and PDGFRβ, but selectivity for CSF1R is >3800-fold [4] (see Supplementary Figure S2). The highly selective nature of this compound limits its off-target activities which is common when targeting this kinase subfamily, so this should increase the interperatability of results from animal studies.
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
colony stimulating factor 1 receptor Hs Inhibitor Inhibition 8.5 pKd - 2
pKd 8.5 (Kd 3.4x10-9 M) [2]
colony stimulating factor 1 receptor Primary target of this compound Hs Inhibitor Inhibition 9.0 pIC50 - 4
pIC50 9.0 (IC50 1x10-9 M) [4]
KIT proto-oncogene, receptor tyrosine kinase Hs Inhibitor Inhibition 5.4 pIC50 - 4
pIC50 5.4 (IC50 3.88x10-6 M) [4]
platelet derived growth factor receptor beta Hs Inhibitor Inhibition 5.2 pIC50 - 4
pIC50 5.2 (IC50 5.86x10-6 M) [4]