SAR405

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

SAR405 是一种高效、选择性 PI3K III 类亚型 Vps34 抑制剂，IC50 为 1.2 nM。

SAR405 is a highly potent and selective PI3K class III isoform Vps34 inhibitor with IC50 of 1.2 nM, inhibits the formation of autophagosomes in GFP-LC3 cells with IC50 of 4 nM; displays no activity against class I and II PI3K isoforms (IC50>10 uM), as well as PIKKs, ATM, ATR and DNA-PK, SMG1; affects both late endosome-lysosome compartments and prevents autophagy, shows synergistic antiproliferative activity in renal tumor cell lines combined with mTOR inhibitor everolimus; enhances the antitumor efficacy of cisplatin in mouse xenograft model of HNSCC.

The activity of SAR405 is next evaluated on a dedicated Vps34 cellular assay using a GFP-FYVE–transfected HeLa cell line.SAR405 prevents autophagy and synergizes with mTOR inhibition in tumor cells. SAR405 prevents autophagosome formation with an IC50 of 42 nM. Treatment of starved cells with SAR405 completely inhibits the conversion to LC3-II in a dose-dependent manner. The effect of SAR405 on autophagy is then investigated. The GFP-LC3 model is used for the HTS and confirmed its activity on starved cells (IC50=419 nM). The conversion of LC3-I into LC3-II is also analyzed by western blotting on wild-type HeLa and H1299 cells.

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SAR-405 | SAR 405

PI3K/Akt/mTOR signaling

PI3K

PI3K

Cancer

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1523406-39-4

443.8506

C19H21ClF3N5O2

>98% (HPLC)

DMSO: ≥ 27 mg/mL

O=C1C=C(N2[C@H](C)COCC2)N=C3N(CC4=CC(Cl)=CN=C4)[C@H](C(F)(F)F)CCN31

4H-Pyrimido[1,2-a]pyrimidin-4-one, 9-[(5-chloro-3-pyridinyl)methyl]-6,7,8,9-tetrahydro-2-[(3R)-3-methyl-4-morpholinyl]-8-(trifluoromethyl)-, (8S)-

(-20℃)

With Ice Pack

≥ 2 years