PIK-III
- Product Name
- PIK-III
- CAS No.
- 1383716-40-2
- Chemical Name
- PIK-III
- Synonyms
- PIK-Ⅲ;PIK-III;Vps34-PIK-III;Vps34 inhibitor PIK-III;Vps34-PIK-III, 10 mM in DMSO;4'-(Cyclopropylmethyl)-N2-4-pyridinyl[4,5'-bipyrimidine]-2,2'-diamine;[4,5'-Bipyrimidine]-2,2'-diamine, 4'-(cyclopropylmethyl)-N2-4-pyridinyl-;4'-(Cyclopropylmethyl)-N2-(pyridin-4-yl)-[4,5'-bipyrimidine]-2,2'-diamine;PI3K,Autophagy,Vps34 PIK III,Vps-34-PIK-III,Inhibitor,Phosphoinositide 3-kinase,Vps34PIKIII,inhibit
- CBNumber
- CB43133178
- Molecular Formula
- C17H17N7
- Formula Weight
- 319.36
- MOL File
- 1383716-40-2.mol
PIK-III Property
- 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 and Precautionary Statements (GHS)
- Symbol(GHS)
-
- Signal word
- Warning
- Hazard statements
-
H302Harmful if swallowed
H315Causes skin irritation
H319Causes serious eye irritation
H335May cause respiratory irritation
- Precautionary statements
-
P261Avoid breathing dust/fume/gas/mist/vapours/spray.
P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.
N-Bromosuccinimide Price
- Product number
- 17002
- Product name
- PIK-III
- Purity
- ≥98%
- Packaging
- 1mg
- Price
- $74
- Updated
- 2024/03/01
- Product number
- 17002
- Product name
- PIK-III
- Purity
- ≥98%
- Packaging
- 5mg
- Price
- $220
- Updated
- 2024/03/01
- Product number
- 17002
- Product name
- PIK-III
- Purity
- ≥98%
- Packaging
- 10mg
- Price
- $365
- Updated
- 2024/03/01
- Product number
- 17002
- Product name
- PIK-III
- Purity
- ≥98%
- Packaging
- 25mg
- Price
- $699
- Updated
- 2024/03/01
- Product number
- AS118254
- Product name
- PIK-III
- Purity
- 98+%
- Packaging
- 25mg
- Price
- $773
- Updated
- 2021/12/16
PIK-III Chemical Properties,Usage,Production
Uses
Vps34-PIK-III is an orally active and selective VPS34 inhibitor (IC50=18 nM). Vps34-PIK-III effectively inhibits autophagy and can be used as a molecular tool. vps34-PIK-III is also a PI3K inhibitor that inhibits the expression of genes in liver cancer stem cells (CSCs)[1][2][3].
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.
Synthesis
1383716-87-7
50-01-1
1383716-40-2
Examples 10a-10v General method for the synthesis of 4'-(cyclopropylmethyl)-N-pyridin-4-yl-4,5'-bipyrimidinyl-2,2'-diamine. Preparation of 4'-(cyclopropylmethyl)-N-pyridin-4-yl-[4,5']bipyrimidinyl-2,2'-diamine (10a): to a (3Z)-1-cyclopropyl-4-(dimethylamino)-3-[2-(pyridin-4-ylamino)pyrimidin-4-yl]but-3-en-2-one (9) (80 mg, 0.247 mmol) of DMF (2.061 mL ) solution was added guanidine hydrochloride (35.3 mg, 0.371 mmol) and potassium carbonate (103 mg, 0.742 mmol) and the reaction mixture was heated at 60 °C for 4 hours. The crude product was purified by reversed-phase HPLC [30-90% organic phase over 15 min], followed by further purification using Biotage silica gel chromatography [10 g SNAP column, 100% DCM to 12% MeOH/DCM] to afford the target product as a white solid (24.72 mg, 31.3% yield).1H NMR (400 MHz, MeOD) δ ppm 0.01-0.14 (m, 2H), 0.39 (q, J = 6.06 Hz, 2H), 0.94-1.10 (m, 1H), 2.87 (d, J = 7.07 Hz, 2H), 7.10 (d, J = 5.05 Hz, 1H), 7.83 (d, J = 6.57 Hz, 2H), 8.30 (d, J = 6.57 Hz , 2H), 8.41 (s, 1H), 8.57 (d, J = 5.05 Hz, 1H). HRMS (ES+) C17H17N7H+ [MH+] calculated value: 320.1624; measured value: 320.1636. UV-LC: 100% UV purity at 254/214 nm; tR = 4.67 min, total run time 7.75 min.
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.
PIK-III Preparation Products And Raw materials
Raw materials
Preparation Products
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