SAR131675

製品コードS2842 バッチS284204

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₁₈H₂₂N₄O₄
	分子量	358.39	CAS No.	1433953-83-3
Solubility (25°C)*	体外	DMSO	72 mg/mL (200.89 mM)
		Water	Insoluble
		Ethanol	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	SAR131675 is a VEGFR3 inhibitor with IC50/K_i of 23 nM/12 nM in cell-free assays, about 50- and 10-fold more selective for VEGFR3 than VEGFR1/2, little activity against Akt1, CDKs, PLK1, EGFR, IGF-1R, c-Met, Flt2 etc.
in vitro	SAR131675 dose dependently inhibits the proliferation of primary human lymphatic cells, induced by the VEGFR-3 ligands VEGFC and VEGFD, with an IC50 of about 20 nM. SAR131675 dose dependently inhibits rh-VEGFR-3–TK activity with an IC50 of 23 nM. SAR131675 inhibits VEGR-3–TK activity with a K_i of about 12 nM. SAR131675 inhibits VEGFR-1–TK activity with an IC50 of > 3 μM and VEGFR-2–TK activity with an IC50 of 235 nM. SAR131675 inhibits VEGFR-1 autophosphorylation with an IC50 of about 1 μM and VEGFR-2 with an IC50 of about 280 nM. SAR131675 moderately inhibits VEGFR-2 and has very little effect on VEGFR-1, showing a good selectivity for VEGFR-3. SAR131675 inhibits VEGFA-induced VEGFR-2 phosphorylation in a dose-dependent manner, with an IC50 of 239 nM. SAR131675 potently inhibits lymphatic cell survival induced by VEGFC and VEGFD with IC50 of 14 nM and 17 nM, respectively. SAR131675 inhibits VEGFA-induced survival with an IC50 of 664 nM. SAR131675, significantly and dose dependently inhibits VEGFC-induced Erk phosphorylation, with an IC50 of about 30 nM. ^[1]
in vivo	In embryonic angiogenesis using the zebrafish model, SAR131675 efficiently impaires embryonic vasculogenesis. SAR131675 at 100 mg/kg/d has significantly reduced the levels of VEGFR-3 and hemoglobin content by about 50%. SAR131675 efficiently abrogates lymphangiogenesis and angiogenesis induced in vivo by FGF2. SAR131675 at a dose of 300 mg/kg is able to inhibit both VEGFR-2 and VEGFR-3 signaling. In the prevention study, 5 weeks treatment with SAR131675 is well tolerated and the number of angiogenic islets in the pancreas of SAR131675-treated mice is significantly decreased by 42%, compared with the vehicle-treated group. In the intervention study, daily oral administration of SAR131675 from week 10 to week 12.5 causes a significant decrease in tumor burden by 62%. Treatment with SAR131675 significantly reduces the tumor volume 24% and 50% at 30 mg/kg/d and 100 mg/kg/d, respectively. ^[1]
特徴	A potent and selective VEGFR-3–tyrosine kinase inhibitor.

プロトコル(参考用のみ)

キナーゼアッセイ	Tyrosine kinase assay
キナーゼアッセイ	Multiwell plates are precoated with a synthetic polymer substrate poly-Glu-Tyr (polyGT 4:1). The reaction is carried out in the presence of kinase buffer (10 ×: 50 mM HEPES buffer, pH 7.4, 20 mM MgCl₂, 0.1 mM MnCl₂, and 0.2 mM Na₃VO₄) supplemented with ATP and dimethyl sulfoxide (DMSO) for the positive control (C⁺) or SAR131675 (ranging from 3 nM–1,000 nM). ATP is used at 30 μM for VEGFR-1 and VEGFR-3 and at 15 μM for VEGFR-2. The phosphorylated poly-GT is probed with a phosphotyrosine specific monoclonal antibody (mAb) conjugated to horseradish peroxidase (HRP; 1/30,000) and developed in the dark with the HRP chromogenic substrate (OPD). The reaction is then stopped by the addition of 100 μL 1.25 M H₂SO₄, and absorbance is determined using an Envision spectrophotometer at 492 nm.
細胞アッセイ	細胞株	HEK cells
	濃度	20 nM
	反応時間	30 minutes
	実験の流れ	Cells were treated with various concentrations of SAR131675.
動物実験	動物モデル	BALB/c mice with 4T1 cells
	投薬量	30 mg/kg/d, 100 mg/kg/d, and 300 mg/kg/d
	投与方法	Oral

参考

[1] Alam A, et al. Mol Cancer Ther, 2012, 11(8), 1637-1649.

カスタマーフィードバック

: , , Neuroscience, 2015, 290C:90-102.

: Data from [Data independently produced by , , Clin Exp Metastasis, 2015, 32(8):789-98]

: Data from [Data independently produced by , , Biochem Biophys Res Commun, 2016, 472(1):182-8.]

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：

Piezo1 regulates meningeal lymphatic vessel drainage and alleviates excessive CSF accumulation [ Nat Neurosci, 2024, 10.1038/s41593-024-01604-8]	PubMed: 38528202
Fibroblasts facilitate lymphatic vessel formation in transplanted heart [ Theranostics, 2024, 14(5):1886-1908]	PubMed: 38505621
VEGFD signaling balances stability and activity-dependent structural plasticity of dendrites [ Cell Mol Life Sci, 2024, 81(1):354]	PubMed: 39158743
Lack of RAMP1 Signaling Suppresses Liver Regeneration and Angiogenesis Following Partial Hepatectomy in Mice [ In Vivo, 2024, 38(5):2261-2270]	PubMed: 39187322
VEGFR-3 signaling restrains the neuron-macrophage crosstalk during neurotropic viral infection [ Cell Rep, 2023, 42(5):112489]	PubMed: 37167063
Rotator cuff healing is regulated by the lymphatic vasculature [ J Orthop Translat, 2023, 38:65-75]	PubMed: 36313978
SAR131675 exhibits anticancer activity on human ovarian cancer cells through inhibition of VEGFR-3/ERK1/2/AKT signaling pathway [ Cell Signal, 2023, 111:110856]	PubMed: 37598918
Lymphangiogenic responses of lymphatic endothelial cells to steady direct-current electric fields [ Cell Adh Migr, 2023, 10.1080/19336918.2023.2271260]	PubMed: 37889090
Lymphangiogenesis contributes to exercise-induced physiological cardiac growth [ J Sport Health Sci, 2022, S2095-2546(22)00037-0]	PubMed: 35218948
Lymphangiogenesis in renal fibrosis arises from macrophages via VEGF-C/VEGFR3-dependent autophagy and polarization [ Cell Death Dis, 2021, 12(1):109]	PubMed: 33479195

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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