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Sotuletinib (BLZ945)

Name: Sotuletinib (BLZ945)
Brand: Selleck Chemicals
SKU: S7725
Rating: 5 (29 reviews)

Catalog No.S7725 Purity:99.99%

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

CAS No. 953769-46-5

Purity & Quality Control

Batch: Purity: 99.99%

99.99

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Signaling Pathway

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
Experimental Result Images	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
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-05-22)
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

References

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)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

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
	Clear solution	2%DMSO 1 40%PEG300 2 5%TWEEN80 3 53%ddH2O	1.6mg/ml (4.02mM)	Taking the 1 mL working solution as an example, add 20 μL of 80 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 530 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.	In vivo Formulation Calculator
Clear solution	5%DMSO 1 Corn oil	2.86mg/ml (7.18mM)	Taking the 1 mL working solution as an example, add 50 μL of 57.1 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	2.0mg/ml (5.02mM)	Taking the 1 mL working solution as an example, add 50 μL of 40 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

Preparing Stock Solutions

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Formulation Calculator (Clear solution)

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

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

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.

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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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