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BLZ945 (Synonyms: BLZ945)

Catalog No.GC12539

BLZ945 (BLZ945) is a potent, selective and brain-penetrant CSF-1R (c-Fms) inhibitor with an IC50 of 1 nM, showing more than 1,000-fold selectivity against its closest receptor tyrosine kinase homologs.

Products are for research use only. Not for human use. We do not sell to patients.

BLZ945 Chemical Structure

Cas No.: 953769-46-5

Size Price Stock Qty
10mM (in 1mL DMSO)
$73.00
In stock
5mg
$68.00
In stock
25mg
$188.00
In stock
100mg
$512.00
In stock

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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell experiment [1]:

Cell lines

BMDM cell line

Preparation method

The solubility of this compound in DMSO is > 19.9 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months.

Reacting condition

6.7 ~ 6700 nM; 96 hrs

Applications

In BMDM cell line, BLZ945 specifically inhibited CSF-1-dependent proliferation (EC50 = 67 nM), and reduced CSF-1R phosphorylation.

Animal experiment [2]:

Animal models

Female MMTV-PyMT transgenic mice

Dosage form

200 mg/kg; p.o.; q.d., for 16 days

Applications

In female MMTV-PyMT transgenic mice, BLZ945 decreased macrophages in tumors and livers, but showed no effect on lung macrophages, circulating monocytes and tumor cell proliferation.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Pyonteck SM, Akkari L, Schuhmacher AJ, Bowman RL, Sevenich L, Quail DF, Olson OC, Quick ML, Huse JT, Teijeiro V, Setty M, Leslie CS, Oei Y, Pedraza A, Zhang J, Brennan CW, Sutton JC, Holland EC, Daniel D, Joyce JA. CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat Med. 2013 Oct;19(10):1264-72.

[2]. Strachan DC, Ruffell B2, Oei Y et al. CSF1R inhibition delays cervical and mammary tumor growth in murine models by attenuating the turnover of tumor-associated macrophages and enhancing infiltration by CD8+ T cells. Oncoimmunology. 2013 Dec 1;2(12):e26968.

Background

BLZ945, also named as 4-[2((1R,2R)-2-Hydroxycyclohexylamino)-benzothiazol-6-yloxyl]-pyridine- 2-carboxylic acid methylamide , is a small molecule inhibitor of CSF-1R kinase with IC50 value of 1.2 nM. [2]
CSF-1R is the receptor for macrophage colony stimulating factor (M-CSF) which mediates the biological effects of this cytokine. The main biological effects of CSF-1R signaling are differentiation, proliferation, migration and survival of precursor macrophages and osteoclasts from the monocytic lineage [1].  
BLZ945 has the potential to treat an array of diseases associated with normal and deregulated function of precursor macrophages and osteoclasts from the monocytic lineage. [14C]BLZ945 metabolites were kinetically and structurally characterized from an in vitro across species comparison study using human hepatocytes and microsomes. Both compounds BLZ945 and M9 have significant anti-proliferative activity against the M-CSF dependent cell line MNFS-60 with EC50 of 71 and 140 mM, respectively. The biotransformation of BLZ945 in human liver micro-omes and recombinant cytochromes occurred predominantly via oxidative routes with also a secondary reductive pathway. [2]
BLZ945 decreased the growth of malignant cells in the mouse mammary tumor virus-driven polyomavirus middle T antigen (MMTV-PyMT) model of mammary carcinogenesis. BLZ945 prevented tumor progression in the keratin 14-expressing human papillomavirus type 16 (K14-HPV-16) transgenic model of cervical carcinogenesis. [3]
References:
[1]. Stanley ER, Berg KL, Einstein DB et al. Biology and action of colony--stimulating factor-1. Mol Reprod Dev. 1997 Jan;46(1):4-10.
[2]. Krauser JA, Jin Y, Walles M et al. Phenotypic and metabolic investigation of a CSF-1R kinase receptor inhibitor (BLZ945) and its pharmacologically active metabolite. Xenobiotica. 2015 Feb;45(2):107-23.
[3]. Strachan DC, Ruffell B2, Oei Y et al. CSF1R inhibition delays cervical and mammary tumor growth in murine models by attenuating the turnover of tumor-associated macrophages and enhancing infiltration by CD8+ T cells. Oncoimmunology. 2013 Dec 1;2(12):e26968.

Chemical Properties

Cas No. 953769-46-5 SDF
Synonyms BLZ945
Chemical Name 4-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-5-yl)oxy)-N-methylpicolinamide
Canonical SMILES O=C(NC)C1=NC=CC(OC2=CC3=C(N=C(N[C@@H]4CCCC[C@H]4O)S3)C=C2)=C1
Formula C20H22N4O3S M.Wt 398.48
Solubility ≥ 19.9mg/mL in DMSO Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
1 mg 5 mg 10 mg
1 mM 2.5095 mL 12.5477 mL 25.0954 mL
5 mM 0.5019 mL 2.5095 mL 5.0191 mL
10 mM 0.251 mL 1.2548 mL 2.5095 mL
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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.
3. All of the above co-solvents are available for purchase on the GlpBio website.

Reviews

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Average Rating: 5 ★★★★★ (Based on Reviews and 38 reference(s) in Google Scholar.)

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