VPS34 Inhibitor, SAR405

Cell permeable: yes

Primary Target
VPS34

Toxicity: Standard Handling (A)

A cell-permeable pyrimido[1,2-a]pyrimidin-6(2H)-one derivative that acts as a potent, selective, and ATP competitive inhibitor of vacuolar protein sorting 34 kinase activity (Vps34; K_d = 1.5 nM, IC₅₀ = 1.2 nM in a biochemical assay, and IC₅₀ = 27 nM in a cell based assay). Does not affect the activity of over 200 other protein kinases including class I and II PI 3 kinases and mTOR (~ 10 µM). However, it displays a weak inhibitory activity against SMG1 at higher concentrations (IC₅₀ = 1 µM). Does not affect the Akt phosphorylation even at higher concentrations (~10 µM), Shown to affect the late endosome-lysosome compartment formation and block the formation of autophagosomes in starved HeLa and H1299 cells (~ 1 µM). Acts synergistically with everolimus to block the proliferation of ACHN and 786-O renal tumor cells.

Ronan, B., et al. 2014. Nat. Chem. Biol.10, 1013.

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

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