| Identification | Back Directory | [Name]
2-Pyridinecarboxamide, 4-[[2-[[(1R,2R)-2-hydroxycyclohexyl]amino]-6-benzothiazolyl]oxy]-N-methyl-, hydrochloride (1:1) | [CAS]
2222138-31-8 | [Synonyms]
Sotuletinib HCl
BLZ945 hydrochloride
Sotuletinib hydrochloride | [Molecular Formula]
C20H22N4O3S.ClH | [MOL File]
2222138-31-8.mol | [Molecular Weight]
434.94 |
| Hazard Information | Back Directory | [Uses]
Sotuletinib (BLZ945) hydrochloride is a potent, selective 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[1]. | [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[1]. 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<0.05)[2]. | [References]
[1] Pyonteck SM, et al. CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat Med. 2013 Oct;19(10):1264-72. DOI:10.1038/nm.3337
[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. DOI:10.4161/onci.26968 |
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