Sotuletinib (BLZ945) is a potent, selective, orally active and brain-penetrant CSF-1R (c-Fms) inhibitor with an IC₅₀ of 1 nM, showing more than 1,000-fold selectivity against its closest receptor tyrosine kinase homologs. Sotuletinib can be used for microglia depletion, and for tumor and CNS-related disease research^[1][2][3][4].

IC50: 1 nM (CSF-1R), 3.2 μM (c-Kit), 4.8 μM (PDGFRβ), 9.1 μM (Flt3)^[1]

Treatment of bone marrow-derived macrophages (BMDMs) with Sotuletinib inhibits CSF-1-dependent proliferation (EC₅₀=67 nM), and decreases CSF-1R phosphorylation, similar to CSF-1R antibody blockade. Sotuletinib also reduces viability of CRL-2467 microglia, Ink4a/Arf ^/ BMDMs (PDG genetic background), and NOD/SCID BMDMs. Importantly, Sotuletinib treatment in culture does not affect proliferation of any PDG-derived tumor cell lines (all Csf-1r-negative), or U-87 MG human glioma cells, and PDG cell tumor sphere formation is unaffected. Thus, Sotuletinib has no direct effects on glioma cells, and perturbs macrophage survival through CSF-1R inhibition^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Sotuletinib (2,000 ppm in diet, 21 days) depletes more than 90% of microglia in C57BL6/J mice^[3].
Sotuletinib hydrochloride (200 mg/kg, p.o., 7 days) depletes more than 90% microglia in C57BL6/J mice, and subsequntenly used for microglia replacement^[4].
Sotuletinib (60-169 mg/kg, p.o., 5 days) dose- and time-dependently depletes microglia in C57BL6/J mice, and newly generated microglia after BLZ945 removal reached normal levels 3 days after last dose^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

398.48

C₂₀H₂₂N₄O₃S

953769-46-5

Solid

Off-white to light brown

O=C(C1=NC=CC(OC2=CC=C3N=C(N[C@H]4[C@H](O)CCCC4)SC3=C2)=C1)NC

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

• [1]. Pyonteck SM, et al. CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat Med. 2013 Oct;19(10):1264-72.  [Content Brief]

  [2]. Strachan DC, et al. 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. 2013 Dec 1;2(12):e26968.  [Content Brief]

  [3]. Chen Y, et al. Spatiotemporally selective astrocytic ATP dynamics encode injury information sensed by microglia following brain injury in mice. Nat Neurosci. 2024 Aug;27(8):1522-1533.  [Content Brief]

  [4]. Frosch M, et al. Microglia-neuron crosstalk through Hex-GM2-MGL2 maintains brain homeostasis. Nature. 2025 Oct;646(8086):913-924.  [Content Brief]

  [5]. Beckmann N, et al. Brain region-specific enhancement of remyelination and prevention of demyelination by the CSF1R kinase inhibitor BLZ945. Acta Neuropathol Commun. 2018 Feb 15;6(1):9.  [Content Brief]