5.33063

VPS34 Inhibitor, SAR405

• Synonym(e): VPS34 Inhibitor, SAR405, Vacuolar Protein Sorting 34 Inhibitor, SAR405, (S)-1-((5-chloropyridin-3-yl)methyl)-8-((R)-3-methylmorpholino)-2-(trifluoromethyl)-3,4-dihydro-1H-pyrimido[1,2-a]pyrimidin-6(2H)-one
• Empirische Formel (Hill-System): C₁₉H₂₁ClF₃N₅O
• CAS-Nummer: 1523406-39-4
• Molekulargewicht: 427.85
• MDL number: MFCD28411361
• UNSPSC Code: 12352200
• NACRES: NA.77
• Assay: ≥96% (HPLC)
• Form: powder
• Storage condition: OK to freeze, protect from light

Eigenschaften

• assay: ≥96% (HPLC)
• Quality Segment: 100
• form: powder
• potency: 1.5 nM K_i
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze, protect from light
• color: off-white
• solubility: DMSO: 50 mg/mL
• storage temp.: −20°C
• SMILES string: FC(F)(F)[C@H]1N(c3[n]([c](cc(n3)N4[C@@H](COCC4)C)=O)CC1)Cc2cncc(c2)Cl
• InChI: 1S/C19H21ClF3N5O2/c1-12-11-30-5-4-26(12)16-7-17(29)27-3-2-15(19(21,22)23)28(18(27)25-16)10-13-6-14(20)9-24-8-13/h6-9,12,15H,2-5,10-11H2,1H3/t12-,15+/m1/s1
• InChI key: SPDQRCUBFSRAFI-DOMZBBRYSA-N

Beschreibung

General description

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.

Biochem/physiol Actions

Primary Target
VPS34

Cell permeable: yes

Preparation Note

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

Other Notes

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

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Disclaimer

Toxicity: Standard Handling (A)

Sicherheitshinweise

• Lagerklasse: 11 - Combustible Solids
• wgk: WGK 3
• flash_point_f: Not applicable
• flash_point_c: Not applicable