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.
Click here for help

Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

✖

View interactive charts of activity data across species
2D Structure
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

✖
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
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

✖
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
References
1. Beckmann N, Giorgetti E, Neuhaus A, Zurbruegg S, Accart N, Smith P, Perdoux J, Perrot L, Nash M, Desrayaud S et al.. (2018)
Brain region-specific enhancement of remyelination and prevention of demyelination by the CSF1R kinase inhibitor BLZ945.
Acta Neuropathol Commun, 6 (1): 9. [PMID:29448957]
2. Czako B, Marszalek JR, Burke JP, Mandal P, Leonard PG, Cross JB, Mseeh F, Jiang Y, Chang EQ, Suzuki E et al.. (2020)
Discovery of IACS-9439, a Potent, Exquisitely Selective, and Orally Bioavailable Inhibitor of CSF1R.
J Med Chem, 63 (17): 9888-9911. [PMID:32787110]
3. Krauser JA, Jin Y, Walles M, Pfaar U, Sutton J, Wiesmann M, Graf D, Pflimlin-Fritschy V, Wolf T, Camenisch G et al.. (2015)
Phenotypic and metabolic investigation of a CSF-1R kinase receptor inhibitor (BLZ945) and its pharmacologically active metabolite.
Xenobiotica, 45 (2): 107-23. [PMID:25180976]
4. Strachan DC, Ruffell B, Oei Y, Bissell MJ, Coussens LM, Pryer N, Daniel D. (2013)
CSF1R inhibition delays cervical and mammary tumor growth in murine models by attenuating the turnover of tumor-associated macrophages and enhancing infiltration by CD8(+) T cells.
Oncoimmunology, 2 (12): e26968. [PMID:24498562]