Sotuletinib hydrochloride - ≥98% , CAS No.2222138-31-8

CAS: 2222138-31-8 Cat. No.: S650346 Molecular Weight: 434.94

GRADE & PURITY ≥98%

Storage

Store at 2-8°C,Desiccated

Shipped In

Wet ice

Overview

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<0.05). MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Form:Solid

Specifications

Specifications & Purity

≥98%

Biochemical and Physiological Mechanisms

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.

Storage

Store at 2-8°C, Desiccated

Shipped In

Wet ice

This product requires cold chain shipping. Ground and other economy services are not available.

Purity

≥98%

Names and Identifiers

• Canonical Smiles: O=C(C1=NC=CC(OC2=CC=C3N=C(N[C@H]4[C@H](O)CCCC4)SC3=C2)=C1)NC.[H]Cl
• Molecular Weight: 434.94

Chemical and Physical Properties

• Solubility: H2O : 100 mg/mL (229.92 mM; Need ultrasonic) DMSO : 100 mg/mL (229.92 mM; Need ultrasonic)