Size | Price | Stock | Qty |
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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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Other Sizes |
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Purity: ≥98%
VPS34 inhibitor 1 (also known as Vps34-IN1, Compound 19, PIK-III analogue) is a potent and selective inhibitor of VPS34 the potential to serve as a chemical tool to modulate autophagy in Vivo. It inhibits VPS34 with an IC50 of 15 nM. VPS34 inhibitor 1 does not significantly inhibit the activity of over 340 additional kinases, including class I and II PI3Ks. Vps34-IN1 induces a rapid dose-dependent dispersal of a specific PtdIns-(3)-P-binding probe from endosome membranes, within one minute, without affecting the ability of class I PI3K to regulate Akt.
Targets |
VPS34 (IC50 = 15 nM)
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ln Vitro |
Compound 19 is extraordinarily selective over other lipid and protein kinases. Compound 19 and PIK-III have comparable abilities to stop the breakdown of the autophagy substrates p62, NCOA4, NBR1, NDP52, and FTH1. Additionally, compound 19 causes cells to produce more lipidated and nonlipidated forms of LC3, which is consistent with earlier studies using PIK-III[1].
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ln Vivo |
The pharmacokinetic profile of analogue 19 is determined in C57BL/6 mice. Oral administration of the compound at a dose of 10 mg/kg results in rapid absorption, moderate mean systemic clearance (30 mL/min/kg, or roughly 33% of hepatic blood flow), and good oral bioavailability (F% = 47). Compound 19 qualifies as a suitable candidate for in vivo studies based on these PK parameters and the cellular activity. When compound 19 is given orally twice daily (BID) at a dose of 50 mg/kg for seven days, LC3-II builds up in a way that is time-dependently consistent with decreased autophagic capacity. It prevents autophagy in living cells[1].
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Cell Assay |
For inhibitor assay, cells are plated and the following day when cells had reached 90%, are treated with dimethyl sulfoxide (DMSO, vehicle) or the indicated concentration of PIK-III or Compound 19, both dissolved in DMSO. After 24 hours, cells are lysed in RIPA supplemented with 1% SDS and mini-EDTA protease inhibitors, homogenized by passage through a Qiashredder column, and the protein is quantified by DC Lowry protein assay.
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Animal Protocol |
C57BL/6 Mice
10 mg/kg(p.o.) or 2 mg/kg(I.V.) oral administration or I.V. |
References |
Molecular Formula |
C21H25N7O
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Molecular Weight |
391.47
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CAS # |
1383716-46-8
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Related CAS # |
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Appearance |
Solid
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SMILES |
CC(C)(CNC1=NC=C(C(=N1)CC2CC2)C3=NC(=NC=C3)NC4=CC=NC=C4)O
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InChi Key |
CC(C)(CNC1=NC=C(C(=N1)CC2CC2)C3=NC(=NC=C3)NC4=CC=NC=C4)O
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InChi Code |
XJTIGGCBXFIZJV-UHFFFAOYSA-N
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Chemical Name |
1-[[4-(cyclopropylmethyl)-5-[2-(pyridin-4-ylamino)pyrimidin-4-yl]pyrimidin-2-yl]amino]-2-methylpropan-2-ol
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Synonyms |
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
DMSO: ~78 mg/mL (199.2 mM)
Water: <1 mg/mL Ethanol: <1 mg/mL |
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Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.5545 mL | 12.7724 mL | 25.5447 mL | |
5 mM | 0.5109 mL | 2.5545 mL | 5.1089 mL | |
10 mM | 0.2554 mL | 1.2772 mL | 2.5545 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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