sotuletinib   Click here for help

GtoPdb Ligand ID: 8250

Synonyms: BLZ 945 | BLZ-945 | BLZ945
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].
The chemical structure of BLZ945 matches that for the INN compound sotuletinib that was surfaced in WHO Proposed list 125.
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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
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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
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Summary of Clinical Use Click here for help
Phase 1/2 clinical trial NCT02829723 is evaluating BLZ945 alone or in combination with the anti-PD-1 mAb spartalizumab (PDR001) in advanced solid tumours. A Phase 2 study to evaluate the validity of CSF1R inhibition as a mechanism to modulate neuroinflammation and enhance remyelination in the brain [1], for the potential treatment of amylotrophic lateral sclerosis (ALS) has been initiated. Click here to link to's full list of BLZ945 studies.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02829723 Phase I/II Study of BLZ945 Single Agent or BLZ945 in Combination With PDR001 in Advanced Solid Tumors Phase 1/Phase 2 Interventional Novartis
NCT04066244 Study of Safety and of the Mechanism of BLZ945 in ALS Patients Phase 2 Interventional Novartis