Sotuletinib (BLZ945) hydrochloride is a potent, selective and brain-penetrant CSF-1R (c-Fms) inhibitor with an IC 50 of 1 nM, showing more than 1,000-fold selectivity against its closest receptor tyrosine kinase homologs. In Vitro Sotuletinib hydrochloride inhibits CSF-1-dependent proliferation (EC 50 =67 nM) in bone marrow-derived macrophages (BMDMs), and decreases CSF-1R phosphorylation, similar to CSF-1R antibody blockade. Sotuletinib hydrochloride also reduces viability of CRL-2467 microglia, Ink4a/Arf ?/? BMDMs (PDG genetic background), and NOD/SCID BMDMs. Importantly, Sotuletinib hydrochloride 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 hydrochloride has no direct effects on glioma cells, and perturbs macrophage survival through CSF-1R inhibition. MCE has not independently confirmed the accuracy of these methods. They are for reference only. In Vivo Mice are treated with Sotuletinib hydrochloride or vehicle, and evaluated for symptom-free survival. Median survival in the vehicle-treated cohort is 5.7 weeks. In striking contrast, Sotuletinib hydrochloride significantly improves long-term survival with 64.3% surviving to the 26-week trial endpoint. This endpoint is chosen because Ink4a/Arf ?/? mice develop spontaneous tumors, including lymphomas and sarcomas, beginning at ~30 weeks. Sotuletinib hydrochloride is well-tolerated over long-term treatment, with no visible side-effects, consistent with histopathological studies. Histological grading revealed high-grade, invasive gliomas in all vehicle-treated mice. By contrast, Sotuletinib hydrochloride-treated animals have significantly less-malignant tumors, and no detectable lesions in 55.6% of asymptomatic mice at the endpoint . Mice receiving Sotuletinib hydrochloride shows reduced CSF1R staining in both cervical tumors and the associated stroma, with a significant decrease in CSF1R + stromal macrophages relative to vehicle-treated mice (P Form:Solid
All
Chemical Reagents
Biomedicine
Organic raw materials
Inorganic chemical industry
intermediate
Agricultural chemicals
Auxiliaries and catalysts
Fragrances and Flavors
Dyes and Pigments
Daily chemical industry
Sotuletinib hydrochloride
CAS number：2222138-31-8 molecular formula：C20H23ClN4O3S
overview
compound introduction
Specs
| Chinese alias | 盐酸索妥替尼 | ||
| English alias | - | ||
| CAS number | 2222138-31-8 | molecular formula | C20H23ClN4O3S |
| molecular weight | 434.94 g/mol | Exact mass | ≥98% |
| PSA | - | logp | - |
numbering system
No numbering system information yet
physicochemical properties
No physical and chemical property information yet
Safety information
No safety information yet
Production methods and uses
No production method and use information yet
Related
upstream information
No upstream information yet
downstream information
No downstream information yet
MSDS
Found 0 shareMSDS
