Sotuletinib (BLZ945)

製品コードS7725 バッチS772506

印刷

化学情報

Chemical Structure Synonyms Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C20H22N4O3S
分子量 398.48 CAS No. 953769-46-5
Solubility (25°C)* 体外 DMSO 80 mg/mL (200.76 mM)
Ethanol 2 mg/mL warmed with 50ºC water bath (5.01 mM)
Water Insoluble
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
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]

プロトコル(参考用のみ)

細胞アッセイ 細胞株 Glioma cell lines, BMDM, CRL-2467, HUVEC and HBMEC cell lines
濃度 ~6700 nM
反応時間 96 hours
実験の流れ

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.
動物実験 動物モデル Female MMTV-PyMT transgenic mice
投薬量 200 mg/kg
投与方法 p.o.

カスタマーフィードバック

, , 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の高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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