SAR405

製品コードS7682 バッチS768201

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	C₁₉H₂₁ClF₃N₅O₂
	分子量	443.85	CAS No.	1523406-39-4
Solubility (25°C)*	体外	DMSO	88 mg/mL warmed with 50ºC water bath (198.26 mM)
		Ethanol	88 mg/mL (198.26 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	SAR405 is a low-molecular-mass kinase inhibitor of PIK3C3/Vps34 (KD 1.5 nM) showing high selectivity and not be active up to 10 μM on class I and class II PI3Ks as well as on mTOR. SAR405 prevents autophagy and synergizes with MTOR (mechanistic target of rapamycin) inhibition in tumor cells.
in vitro	SAR405 is an inhibitor that was highly specific for Vps34 with regard to protein kinases and other phosphoinositide kinases. SAR405 has an IC50 of 1 nM in the phosphorylation of a PtdIns substrate by human recombinant Vps34 enzyme. This compound shows a binding equilibrium constant KD of 1.52 ± 0.77 nM (± s.d.) and a dissociation rate constant, k_off, of 3.03 ± 0.55 10⁻³/s, corresponding to a residence half-life, t_1/2, of 3.8 min. SAR405 does not affect the Akt phosphorylation at concentrations up to 10 μM in the PC3 cell line. SAR405 affects vesicle trafficking from late endosomes to lysosomes. It is also a potent autophagy inhibitor^[1].
in vivo	SAR405 is a first-in-class, selective, and ATP-competitive PI3K class III (PIK3C3) isoform Vps34 inhibitor.

プロトコル(参考用のみ)

細胞アッセイ	細胞株	GFP-LC3 HeLa cells
	濃度	1 μM
	反応時間	4 h
	実験の流れ	GFP-LC3 HeLa cells are starved for 2 h in EBSS plus 10 μM hydroxychloroquine with Vps34 compound or DMSO. For mTOR inhibitor, GFP-LC3 H1299 cells are treated with 1 μM AZD8055 for 4 h in fed conditions (DMEM, 10% FCS, 1 mM L-glutamine with SAR405 or DMSO. Cells are then fixed with 4% PFA, and nuclei are stained using 2 μg/ml Hoechst 33342. Fluorescence is analyzed using an imaging cytometer. Cells are considered positive when there are more than four green spots per cell, with a total of 25 fields acquired. The activity of the product is estimated.
動物実験	動物モデル	Nude mice
	投薬量	2 mg/kg
	投与方法	s.c.

参考

カスタマーフィードバック

: Data from [Data independently produced by , , Urol Oncol, 2018, 36(4):160.e1-160.e13]

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：

Intercellular transfer of cancer cell invasiveness via endosome-mediated protease shedding [ Nat Commun, 2024, 15(1):1277]	PubMed: 38341434
Combining VPS34 inhibitors with STING agonists enhances type I interferon signaling and anti-tumor efficacy [ Mol Oncol, 2024, 10.1002/1878-0261.13619]	PubMed: 38506049
Targeting autophagy as a therapeutic strategy in pediatric acute lymphoblastic leukemia [ Sci Rep, 2024, 14(1):4000]	PubMed: 38369625
Inhibition of phosphoglycerate dehydrogenase induces ferroptosis and overcomes enzalutamide resistance in castration-resistant prostate cancer cells [ Drug Resist Updat, 2023, 70:100985]	PubMed: 37423117
Class 3 PI3K coactivates the circadian clock to promote rhythmic de novo purine synthesis [ Nat Cell Biol, 2023, 25(7):975-988]	PubMed: 37414850
TECPR1 is activated by damage-induced sphingomyelin exposure to mediate noncanonical autophagy [ EMBO J, 2023, 42(17):e113105]	PubMed: 37409525
Partial inhibition of class III PI3K VPS-34 ameliorates motor aging and prolongs health span [ PLoS Biol, 2023, 21(7):e3002165]	PubMed: 37432924
mTOR inhibition attenuates chemosensitivity through the induction of chemotherapy resistant persisters [ Nat Commun, 2022, 13(1):7047]	PubMed: 36396656
Rapalogs downmodulate intrinsic immunity and promote cell entry of SARS-CoV-2 [ J Clin Invest, 2022, 132(24)e160766]	PubMed: 36264642
Autophagy profiling in single cells with open source CellProfiler-based image analysis [ Autophagy, 2022, 10.1080/15548627.2022.2065617]	PubMed: 35435815

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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