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PIK-III
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
PIK-III图片
CAS NO:1383716-40-2
包装与价格:
包装价格(元)
5mg电议
25mg电议

产品介绍
PIK-III 是一种有效的选择性 VPS34 抑制剂,IC50 为 18 nM。
Cas No.1383716-40-2
化学名4'-(cyclopropylmethyl)-N2-(pyridin-4-yl)-[4,5'-bipyrimidine]-2,2'-diamine
Canonical SMILESNC1=NC=C(C2=NC(NC3=CC=NC=C3)=NC=C2)C(CC4CC4)=N1
分子式C17H17N7
分子量319.36
溶解度≥ 31.9mg/mL in DMSO
储存条件Store at -20℃
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.
Shipping ConditionEvaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
产品描述

IC50: 18 nM for VPS34

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].

Clinical trial: Up to now, PIK-III is still in the preclinical development stage.

Reference:
[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.