| Identification | Back Directory | [Name]
PIK-III | [CAS]
1383716-40-2 | [Synonyms]
PIK-III
Vps34-PIK-III
Vps34 inhibitor PIK-III
4'-(Cyclopropylmethyl)-N2-4-pyridinyl[4,5'-bipyrimidine]-2,2'-diamine
[4,5'-Bipyrimidine]-2,2'-diamine, 4'-(cyclopropylmethyl)-N2-4-pyridinyl- | [Molecular Formula]
C17H17N7 | [MOL File]
1383716-40-2.mol | [Molecular Weight]
319.36 |
| Chemical Properties | Back Directory | [Boiling point ]
657.4±65.0 °C(Predicted) | [density ]
1.380±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
≥31.9 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH | [form ]
solid | [pka]
6.19±0.26(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Biological Activity]
pik-iii is a vps34 inhibitor and is able to inhibit autophagy.vps34 kinase has been found to be responsible for synthesis and deposition of phosphatidylinositol-3-phosphate at autophagosome formation sites, resulting in the recruitment of ptdins(3)p-binding proteins. | [in vitro]
in previous study, pik-iii was identified as a selective inhibitor of vps34 binding in a hydrophobic pocket. in addition, pik-iii could acutely inhibit the autophagy and lipidation of lc3, which led to the stabilization of autophagy substrates. moreover, substrates such as ncoa4 were identified by conducting ubiquitin-affinity proteomic assay on pik-iii-treated cells, which accumulated in cells with atg7 deficience and co-localized with autolysosomes. ncoa4 could bind ferritin heavy chain-1 directly to target the iron-binding ferritin complex following starvation or iron depletion [1]. | [in vivo]
animal study showed that pik-iii-treated ncoa4-/- mice had a profound accumulation of iron in splenic macrophages that were important for iron reutilization from engulfed red blood cells. in summary, such in vivo results provided a novel mechanism for selective autophagy of ferritin and revealed a previously untouched role for autophagy and ncoa4 in the control of in-vivo iron homeostasis [1]. | [IC 50]
18 nm for vps34 | [References]
[1] dowdle we et al. selective vps34 inhibitor blocks autophagy and uncovers a role for ncoa4 in ferritin degradation and iron homeostasis in vivo. nat cell biol. 2014 nov;16(11):1069-79. |
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