BLZ945

Catalog No.S7725

For research use only.

BLZ945 is an orally active, potent and selective CSF-1R inhibitor with IC50 of 1 nM, >1000-fold selective against its closest receptor tyrosine kinase homologs.

BLZ945 Chemical Structure

CAS No. 953769-46-5

Selleck's BLZ945 has been cited by 21 publications

Purity & Quality Control

Choose Selective CSF-1R Inhibitors

Biological Activity

Description BLZ945 is an orally active, potent and selective CSF-1R inhibitor with IC50 of 1 nM, >1000-fold selective against its closest receptor tyrosine kinase homologs.
Targets
CSF-1R [1]
(Cell-free assay)
1 nM
In vitro

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. [1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
mouse M-NFS-60 cells M3fTOWFvfGmycn;sbYZmemG2aY\lJIF{e2G7 MV3BcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IH3veZNmKE1vTl\TMVYxKGOnbHzzJIhiemKxcnnu[{BEW0ZzLDDFR|UxKD1iMD6wO|Eh|ryPLh?= M{f4dlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7MkmzNFAxLz5{OUK5N|AxODxxYU6=
Assay
Methods Test Index PMID
Western blot pCSF1R / tCSF1R / pAKT / tAKT / p-mTOR / mTOR / pERK / ERK / p-NFKB / NFKB / p-P70S6K / P70S6K / Arg-1 30956894
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. [1] 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. [2]

Protocol (from reference)

Cell Research:[1]
  • Cell lines: Glioma cell lines, BMDM, CRL-2467, HUVEC and HBMEC cell lines
  • Concentrations: ~6700 nM
  • Incubation Time: 96 hours
  • Method: 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.
Animal Research:[2]
  • Animal Models: Female MMTV-PyMT transgenic mice
  • Dosages: 200 mg/kg
  • Administration: p.o.

Solubility (25°C)

In vitro

DMSO 79 mg/mL
(198.25 mM)
Water Insoluble
Ethanol '3 mg/mL warmed

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
4% DMSO+30% PEG 300+ddH2O
For best results, use promptly after mixing.

2.5mg/mL

Chemical Information

Molecular Weight 398.48
Formula

C20H22N4O3S

CAS No. 953769-46-5
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CNC(=O)C1=NC=CC(=C1)OC2=CC3=C(C=C2)N=C(S3)NC4CCCCC4O

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

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%DMSO %

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04066244 Recruiting Drug: BLZ945 Amyotrophic Lateral Sclerosis Novartis Pharmaceuticals|Novartis December 30 2019 Phase 2
NCT02829723 Active not recruiting Drug: BLZ945|Drug: PDR001 Advanced Solid Tumors Novartis Pharmaceuticals|Novartis October 21 2016 Phase 1|Phase 2

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

Question 1:
Does this molecule bind to any neurogenesis inhibiting enzymes? Which of the csf1r inhibitors is the most specific?

Answer:
The IC50 of this compound to CSF1R is about 0.001uM, C-Kit 3.2uM and PDGFR-β 4.8uM. So it is relative specific to CSF1R.

Question 2:
We want to deliver the drug by oral gavage to mice, can you provide some advice about formulation?

Answer:
S7725 BLZ945 can be dissolved in 0.5% CMC Na+1% Tween 80 at 20 mg/ml as a suspension.

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