Home Protein Tyrosine Kinase CSF-1R inhibitor Sotuletinib (BLZ945) For research use only.

Sotuletinib (BLZ945)

Sotuletinib (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.

Sotuletinib (BLZ945) Chemical Structure

Sotuletinib (BLZ945) Chemical Structure

CAS No. 953769-46-5

Purity & Quality Control

Sotuletinib (BLZ945) Related Products

Signaling Pathway

CSF-1R Signaling Pathways

CSF-1R Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
mouse M-NFS-60 cells Antiproliferative assay Antiproliferative activity against mouse M-NFS-60 cells harboring CSF1, EC50 = 0.071 μM. 29293000
Click to View More Cell Line Experimental Data

Biological Activity

Description Sotuletinib (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 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 Research 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.
Experimental Result Images Methods Biomarkers Images PMID
Western blot pCSF1R / tCSF1R / pAKT / tAKT / p-mTOR / mTOR / pERK / ERK / p-NFKB / NFKB / p-P70S6K / P70S6K / Arg-1 30956894
In Vivo
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]
Animal Research Animal Models Female MMTV-PyMT transgenic mice
Dosages 200 mg/kg
Administration p.o.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT04066244 Active not recruiting
Amyotrophic Lateral Sclerosis
Novartis Pharmaceuticals|Novartis
 December 30 2019 Phase 2
NCT02829723 Terminated
Advanced Solid Tumors
Novartis Pharmaceuticals|Novartis
 October 21 2016 Phase 1|Phase 2

Chemical Information & Solubility

Molecular Weight 398.48 Formula

C20H22N4O3S
CAS No. 953769-46-5 SDF Download Sotuletinib (BLZ945) SDF
Smiles CNC(=O)C1=NC=CC(=C1)OC2=CC3=C(C=C2)N=C(S3)NC4CCCCC4O
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 80 mg/mL ( (200.76 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 2 mg/mL

Water : Insoluble


Molecular Weight Calculator

In vivo
Batch:

Add solvents to the product individually and in order.


In vivo Formulation Calculator

Preparing Stock Solutions

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo Formulation Calculator (Clear solution)

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

mg/kg g μL

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.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

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.

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

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.

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.

Tags: buy Sotuletinib (BLZ945) | Sotuletinib (BLZ945) supplier | purchase Sotuletinib (BLZ945) | Sotuletinib (BLZ945) cost | Sotuletinib (BLZ945) manufacturer | order Sotuletinib (BLZ945) | Sotuletinib (BLZ945) distributor