product name BLZ945
Description: BLZ945 is a potent, orally bioactive, and selective CSF-1R inhibitor with IC50 of 1 nM, >1000-fold selective against its closest receptor tyrosine kinase homologs. It showed effects of CSF1R inhibition on other tumor-infiltrating immune cells. BLZ945 decreases the growth of malignant cells in the mouse mammary tumor virus-driven polyomavirus middle T antigen (MMTV-PyMT) model of mammary carcinogenesis. BLZ945 prevents tumor progression in the keratin 14-expressing human papillomavirus type 16 (K14-HPV-16) transgenic model of cervical carcinogenesis.
References: Nat Med. 2013 Oct;19(10):1264-72; Oncoimmunology. 2013 Dec 1;2(12):e26968.
398.48
Formula
C20H22N4O3S
CAS No.
953769-46-5
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 79 mg/mL (198.3 mM)
Water: <1 mg/mL
Ethanol: 3 mg/mL (7.5 mM)
Solubility (In vivo)
4% DMSO+30% PEG 300+ddH2O: 2.5 mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/1940940
| In Vitro |
In vitro activity: In bone marrow-derived macrophages (BMDMs), BLZ945 specifically inhibits CSF-1-dependent proliferation with EC50 of 67nM, and decreases CSF-1R phosphorylation. BLZ945 blocks the reciprocal effects between macrophages and glioma cells on the survival, proliferation and/ or polarization of each other to promote tumorigenesis. Kinase Assay: Cell Assay: 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. |
|---|---|
| In Vivo | In glioma-bearing mice, BLZ945 blocks tumor progression and significantly improves survival via CSF-1R inhibition. BLZ945 also inhibits orthotopic tumor growth of patient-derived proneural tumor spheres and cell lines in vivo. BLZ945 (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. |
| Animal model | Female MMTV-PyMT transgenic mice |
| Formulation & Dosage | Dissolved in 20% Captisol; 200 mg/kg; p.o. |
| References | Nat Med. 2013 Oct;19(10):1264-72; Oncoimmunology. 2013 Dec 1;2(12):e26968. |
