Sotuletinib

SKU: orb1301056

Description

Sotuletinib

Research Area

Signal Transduction

Key Properties

• CAS Number: 953769-46-5
• MW: 398.48
• Purity: 98.09%
• Formula: C₂₀H₂₂N₄O₃S
• SMILES: CNC(=O)c1cc(Oc2ccc3nc(N[C@@H]4CCCC[C@H]4O)sc3c2)ccn1
• Target: CSF-1R,c-Fms
• Solubility: DMSO:257 mg/mL (644.95 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:5 mg/mL (12.55 mM);Ethanol:3 mg/mL (7.53 mM);H2O:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  FLT3:9.1 μM|PDGFRβ:4.8 μM|CSF1R:1 nM|CSF1R:67 nM (EC50)|c-Kit:3.2 μM
• In Vivo:
  In glioma-bearing mice, Sotuletinib blocks tumor progression and significantly improves survival via CSF-1R inhibition. Sotuletinib also inhibits orthotopic tumor growth of patient-derived proneural tumor spheres and cell lines in vivo. Sotuletinib (200 mg/kg, p.o.) decreases the growth of malignant cells in both mouse mammary tumor virus-driven polyomavirus middle T antigen (MMTV-PyMT) model of mammary carcinogenesis and keratin 14-expressing human papillomavirus type 16 (K14-HPV-16) transgenic model of cervical carcinogenesis.
• In Vitro:
  In bone marrow-derived macrophages (BMDMs), Sotuletinib specifically inhibits CSF-1-dependent proliferation with EC50 of 67 nM, and decreases CSF-1R phosphorylation. Sotuletinib blocks the reciprocal effects between macrophages and glioma cells on the survival, proliferation and/ or polarization of each other to promote tumorigenesis.
• Cell Research:
  Cell growth rate is determined using the MTT cell proliferation kit. Briefly, cells are plated in triplicate in 96-well plates: 1,000 cells per well for glioma cell lines, 5 x 1,000 cells per well for BMDM and CRL-2467, and 2.5 x 1,000 cells per well for HUVEC and HBMEC cell lines. For all experiments, media is changed every 48 h. Cells are grown in the presence or absence of 6.7–6,700 nM of BLZ945, or 8 μg/mL of CSF-1R neutralizing antibody. BMDM and CRL-2467 cells were supplemented with 10 ng/mL and 30 ng/ mL recombinant mouse CSF-1, respectively. Reduction of the MTT substrate is detected by colorimetric analysis using a plate reader as per the manufacturer's protocol, and measured at 595 nm and 750 nm on a spectraMax 340pc plate reader.(Only for Reference)

Storage & Handling

• Storage: keep away from direct sunlight,keep away from moisture,store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

BLZ 945, BLZ945, BLZ-945, CSF-1 receptor, CSF1R, CSF-1R, colony stimulating factor 1 receptor, c-Fms, cFms, Inhibitor, inhibit, Sotuletinib

Compound Identifiers

PubChem CID

46184986