VPS34 inhibitor 1 (Compound 19)

製品コードS8456 バッチS845604

印刷

化学情報

Synonyms

PIK-III analogue

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₂₁H₂₅N₇O

分子量

391.47

CAS No.

1383716-46-8

Solubility (25°C)*

体外

DMSO

78 mg/mL (199.24 mM)

Water

Insoluble

Ethanol

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension

CMC-NA

≥5mg/ml

Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

* <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	VPS34 inhibitor 1 (Compound 19, PIK-III analogue) is a potent and selective inhibitor of VPS34 with an IC50 of 15 nM.
in vitro	VPS34 inhibitor 1 (Compound 19) is extraordinarily selective over other lipid and protein kinases. Its ability to prevent the degradation of autophagy substrates p62, NCOA4, NBR1, NDP52, and FTH1 is similar to PIK-III. In addition, treatment of cells with this compound leads to an increase in the lipidated and nonlipidated forms of LC3 similar to previous reports using PIK-III^[1].
in vivo	VPS34 inhibitor 1 (Compound 19) was evaluated for its pharmacokinetic profile in C57BL/6 mice. After oral administration at 10 mg/kg, it was rapidly absorbed and showed moderate mean systemic clearance (30 mL/min/kg, approximately 33% of hepatic blood flow), with good oral bioavailability (F% = 47). Based on these PK parameters and the cellular activity, this compound constitutes a suitable candidate for in vivo studies. Upon oral administration at 50 mg/kg twice a day (BID) for 7 days, LC3-II accumulates consistent with reduced autophagic capacity in time-dependent manner. It inhibits autophagy in vivo^[1].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	U2OS cells
	濃度	0, 1, 5, 10 μM
	反応時間	24 h
	実験の流れ	For inhibitor assay, cells are plated and the following day when cells had reached 90%, are treated with dimethyl sulfoxide (DMSO, vehicle) or the indicated concentration of PIK-III or VPS34 inhibitor 1 (Compound 19), both dissolved in DMSO. 24 hours later, cells are lysed in RIPA supplemented with 1% SDS and mini-EDTA protease inhibitors, homogenized by passage through a Qiashredder column and the protein is quantified by DC Lowry protein assay.
動物実験	動物モデル	C57BL/6 Mice
	投薬量	10 mg/kg(p.o.) or 2 mg/kg(I.V.)
	投与方法	oral administration or I.V.

参考

https://pubmed.ncbi.nlm.nih.gov/26819669/

カスタマーフィードバック

: Data from [Data independently produced by , , Oncotarget, 2017, 8(24):38099-38112]

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：

PROX1 induction by autolysosomal activity stabilizes persister-like state of colon cancer via feedback repression of the NOX1-mTORC1 pathway [ Cell Rep, 2023, S2211-1247(23)00530-2]	PubMed: 37224811
Upregulation of the EGFR/MEK1/MAPK1/2 signaling axis as a mechanism of resistance to antiestrogen‑induced BimEL dependent apoptosis in ER+ breast cancer cells [ Int J Oncol, 2023, 62(2)20]	PubMed: 36524361
Endosomal phosphatidylinositol 3-phosphate controls synaptic vesicle cycling and neurotransmission [ EMBO J, 2022, 10.15252/embj.2021109352]	PubMed: 35318705
Subtractive CRISPR screen identifies the ATG16L1/vacuolar ATPase axis as required for non-canonical LC3 lipidation [ Cell Rep, 2021, 37(4):109899]	PubMed: 34706226
Identification of Required Host Factors for SARS-CoV-2 Infection in Human Cells [ Cell, 2020, S0092-8674(20)31394-5]	PubMed: 33147445
Subtractive CRISPR screen identifies factors involved in non-canonical LC3 lipidation. [ bioRxiv, 2020, 10.1101/2020.11.18.388306]	PubMed: None
The Chick Chorioallantoic Membrane (CAM) Assay as a Three-dimensional Model to Study Autophagy in Cancer Cells [ Bio Protoc, 2019, 9(13):e3290]	PubMed: 33654803
Lysosomal regulation of cholesterol homeostasis in tuberous sclerosis complex is mediated via NPC1 and LDL-R. [Filippakis H, et al. Oncotarget, 2017, 8(24):38099-38112]	PubMed: 28498820

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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