VPS34-IN1 (VPS34-IN-1) is a novel and potent Vps34 (vacuolar protein sorting 34) inhibitor with potential antitumor activity. It has an IC50 of 25 nM for Vps34 inhibition and no activity for 350 closely related lipid or protein kinases. Phosphorylation of PtdIns (phosphatidylinositol) at endosomal membranes by the Vps34 class III PI3K results in PtdIns(3)P, which controls membrane trafficking processes by attracting a subset of proteins with PtdIns(3)P-binding PX (phox homology) and FYVE domains.
Physicochemical Properties
| Molecular Formula | C21H24CLN7O |
| Molecular Weight | 425.9146 |
| Exact Mass | 425.173 |
| Elemental Analysis | C, 59.22; H, 5.68; Cl, 8.32; N, 23.02; O, 3.76 |
| CAS # | 1383716-33-3 |
| Related CAS # | 1383716-33-3 |
| PubChem CID | 57404276 |
| Appearance | White to off-white Solid powder |
| Density | 1.4±0.1 g/cm3 |
| Boiling Point | 693.8±65.0 °C at 760 mmHg |
| Flash Point | 373.4±34.3 °C |
| Vapour Pressure | 0.0±2.3 mmHg at 25°C |
| Index of Refraction | 1.689 |
| LogP | 3.7 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 30 |
| Complexity | 549 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | ClC1C([H])=C(C([H])=C([H])N=1)N([H])C1=NC([H])=C([H])C(C2=C([H])N=C(N([H])C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])O[H])N=C2C([H])([H])C2([H])C([H])([H])C2([H])[H])=N1 |
| InChi Key | AWNXKZVIZARMME-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C21H24ClN7O/c1-21(2,30)12-26-19-25-11-15(17(29-19)9-13-3-4-13)16-6-8-24-20(28-16)27-14-5-7-23-18(22)10-14/h5-8,10-11,13,30H,3-4,9,12H2,1-2H3,(H,25,26,29)(H,23,24,27,28) |
| Chemical Name | 1-[[5-[2-[(2-chloropyridin-4-yl)amino]pyrimidin-4-yl]-4-(cyclopropylmethyl)pyrimidin-2-yl]amino]-2-methylpropan-2-ol |
| Synonyms | VPS34IN1; VPS34-IN1; VPS34 IN1 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | Vps34 (IC50 = 4 nM) |
| ln Vitro | Administration of VPS34-IN1 to cells induces a rapid dose-dependent dispersal of a specific PtdIns(3)P-binding probe from endosome membranes, within 1min, without affecting the ability of class I PI3K to regulate Akt. Additionally, it has the ability to quickly reduce SGK3 phosphorylation by between 50 and 60 percent in just one minute. When it comes to SGK2 isoforms lacking a PtdIns(3)P-binding PX domain, VPS34-IN1 has no inhibitory effect[1]. |
| References |
[1]. Characterization of VPS34-IN1, a selective inhibitor of Vps34, reveals that the phosphatidylinositol 3-phosphate-binding SGK3 protein kinase is a downstream target of class III phosphoinositide 3-kinase. Biochem J. 2014 Nov 1;463(3):413-27. [2]. Prolonged inhibition of class I PI3K promotes liver cancer stem cell expansion by augmenting SGK3/GSK-3β/β-catenin signaling. J Exp Clin Cancer Res. 2018 Jun 25;37(1):122. [3]. Autophagy in Cancer: Regulation by Small Molecules. Trends Pharmacol Sci. 2018 Dec;39(12):1021-1032. |
Solubility Data
| Solubility (In Vitro) |
DMSO: ~85 mg/mL (~199.6 mM) Ethanol: ~85 mg/mL (~199.6 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.87 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.87 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (5.87 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3479 mL | 11.7396 mL | 23.4791 mL | |
| 5 mM | 0.4696 mL | 2.3479 mL | 4.6958 mL | |
| 10 mM | 0.2348 mL | 1.1740 mL | 2.3479 mL |