Vps34-IN-4

SKU: orb1299362

Description

VPS34 inhibitor 1 (Compound 19, PIK-III analogue)

Research Area

Cell Biology, Signal Transduction

Key Properties

• CAS Number: 1383716-46-8
• MW: 391.47
• Purity: 98.60%
• Formula: C₂₁H₂₅N₇O
• SMILES: CC(C)(O)CNc1ncc(c(CC2CC2)n1)-c1ccnc(Nc2ccncc2)n1
• Target: Autophagy,PI3K
• Solubility: DMSO:78 mg/mL (199.25 mM)

Bioactivity

• Target IC50:
  VPS34:15 nM
• In Vivo:
  The pharmacokinetic profile of analogue 19 is determined in C57B-/- mice. After oral administration at 10 mg/kg the compound is 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 an the cellular activity, compound 19 constitutes a suitable andidate for in vivo studies.?Upon oral administration of compound 19 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
• In Vitro:
  VPS34 inhibitor 1 (Compound 19, PIK-III analogue) is extraordinarily Selective over Other lipid and protein kinases the ability of compound 19 to preven the degradation of autophagy substratees p62, NCOA4, NBR1, NDP52, and FTH1 is similar to PIK-III. In addition, treatment of cells with compound 19 leads to an increase in the lipidated and nonlipidated forms of LC3 similar to previous reports using PIK-III.
• Cell Research:
  Cell lines: U2OS cells concentration : 0, 1, 5, 10 μM. Incubation Time: 24 h.Method: For inhibitor assay, cells are plated an the following day when cells had reached 90%, are treated with dimethyl sulfoxide (DMSO, Vehicle) o the indicated concentration of PIK-III or 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 an the protein is quantified by DC Lowry protein assay.
• Animal Research:
  Animal Models: C57B-/- mice. Formulation: PG (20% v/v). Dosages: 10 mg/kg(p.o.) or 2 mg/kg(I.V.).Administration: oral administration or I.V.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Disclaimer: For research use only

Alternative Names

Autophagy, Compound 19, PIK-III analogue, degradation, lysosomal, oral, Inhibitor, inhibit, PI3K, PIK-III analogue, Phosphoinositide 3-kinase, selective, VPS34, Vps34, VPS34 inhibitor 1, VPS34 inhibitor 1 (Compound 19, PIK III analogue), VPS34 inhibitor 1 (Compound 19, PIKIII analogue), VPS-34 inhibitor 1 (Compound 19, PIK-III analogue)

Compound Identifiers

PubChem CID

67983918