Sotuletinib (BLZ945)

Catalog No.S7725 Batch:S772511

Technical Data

Formula

C₂₀H₂₂N₄O₃S

Molecular Weight

398.48

CAS No.

953769-46-5

Solubility (25°C)*

In vitro

DMSO

80 mg/mL (200.76 mM)

Ethanol

5 mg/mL (12.54 mM)

Water

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution	5%DMSO 1 Corn oil	2.86mg/ml	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	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.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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 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]

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 Assay:^{^[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 Study:^{^[2]}	Animal Models Female MMTV-PyMT transgenic mice Dosages 200 mg/kg Administration p.o.

Cell Assay:^{^[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 Study:^{^[2]}

Animal Models
Female MMTV-PyMT transgenic mice
Dosages
200 mg/kg
Administration
p.o.

References

Customer Product Validation

: , , Clin Cancer Res, 2017, 23(20):6021-6030

: Data from [Data independently produced by , , Cancer Res, 2018, 78(15):4253-4269]

: Data from [Data independently produced by , , Clin Cancer Res, 2016, 22(15):3849-59.]

Selleck's Sotuletinib (BLZ945) has been cited by 32 publications

Lactate dehydrogenase A regulates tumor-macrophage symbiosis to promote glioblastoma progression [ Nat Commun, 2024, 15(1):1987]	PubMed: 38443336
Human microglia maturation is underpinned by specific gene regulatory networks [ Immunity, 2023, 56(9):2152-2171.e13]	PubMed: 37582369
Engineering an inhibitor-resistant human CSF1R variant for microglia replacement [ J Exp Med, 2023, 220(3)e20220857]	PubMed: 36584406
Hypoxia-driven protease legumain promotes immunosuppression in glioblastoma [ Cell Rep Med, 2023, S2666-3791(23)00415-9]	PubMed: 37858339
LDHA-regulated tumor-macrophage symbiosis promotes glioblastoma progression [ Res Sq, 2023, 10.1146/annurev-genet-022123-113904]	PubMed: 37886538
Patient-Specific Vascularized Tumor Model: Blocking TAM Recruitment with Multispecific Antibodies Targeting CCR2 and CSF-1R [ bioRxiv, 2023, 2023.11.28.568627]	PubMed: 38076998
LDHA-regulated tumor-macrophage symbiosis promotes glioblastoma progression [ Res Sq, 2023, rs.3.rs-3401154]	PubMed: 37886538
Integrative analysis of drug response and clinical outcome in acute myeloid leukemia [ Cancer Cell, 2022, S1535-6108(22)00312-9]	PubMed: 35868306
CSF-1 maintains pathogenic but not homeostatic myeloid cells in the central nervous system during autoimmune neuroinflammation [ Proc Natl Acad Sci U S A, 2022, 119(14):e2111804119]	PubMed: 35353625
Blocking iASPP/Nrf2/M-CSF axis improves anti-cancer effect of chemotherapy-induced senescence by attenuating M2 polarization [ Cell Death Dis, 2022, 13(2):166]	PubMed: 35190529

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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