| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg | |||
| Other Sizes |
Purity: ≥98%
Autophinib is a novel and potent autophagy inhibitor, which inhibits starvation-induced or rapamyc induced autophagy. It acts by targeting the lipid kinase VPS34 with IC50 values of 90, 40 and 19 nM, respectively. Autophagy is a critical regulator of cellular homeostasis and metabolism. Interference with this process is considered a new approach for the treatment of disease, in particular cancer and neurological disorders. Therefore, novel small-molecule autophagy modulators such as autophinib are in high demand. Autophinib was identified by means of a phenotypic assay monitoring the formation of autophagy-induced puncta, indicating accumulation of the lipidated cytosolic protein LC3 on the autophagosomal membrane. Target identification and validation revealed that autophinib inhibits autophagy induced by starvation or rapamycin by targeting the lipid kinase VPS34.
| Targets |
Lipid kinase VPS34 (Class III Phosphatidylinositol 3-Kinases) [1]
|
||
|---|---|---|---|
| ln Vitro |
In starved MCF7-LC3 cells, autophinib (0.01-1 μM) suppresses LC3 lipidation to generate LC3-II in a dose-dependent manner. Autophinib dose-dependently suppressed autophagy-induced p62 degradation in MCF7-LC3 cells, which is consistent with its inhibition of autophagic flux [1]. By triggering apoptosis (EC50 234 nM) in MCF7 cells, autophinib increases cell death (EC50 264 nM) in starved cells relative to fed cells [1].
1. Potent autophagy inhibitory activity: Autophinib is identified as a potent autophagy inhibitor through a phenotypic assay that monitors the formation of autophagy-induced puncta. These puncta indicate the accumulation of the lipidated cytosolic protein LC3 on the autophagosomal membrane, and Autophinib interferes with this process [1] 2. Inhibits autophagy induced by specific stimuli: Autophinib effectively inhibits autophagy induced by starvation or rapamycin in relevant cell models [1] 3. Activity in multiple cell lines: The autophagy inhibitory effect of Autophinib is observed in various cell lines, including HEK293, HeLa, and MCF-7 cells [1] |
||
| ln Vivo |
|
||
| Cell Assay |
1. Phenotypic assay for autophagy-induced puncta detection: Cells (including HEK293, HeLa, MCF-7 cells) are cultured and subjected to conditions that induce autophagy (such as starvation or rapamycin treatment) in the presence or absence of Autophinib. The formation of autophagy-induced puncta, which reflect the accumulation of lipidated LC3 on autophagosomal membranes, is monitored and analyzed. This assay is used to identify and confirm the autophagy inhibitory activity of Autophinib [1]
2. Autophagy inhibition validation assay under different induction conditions: Cells are divided into groups: non-induced control group, starvation-induced autophagy group, rapamycin-induced autophagy group, and Autophinib-treated groups (under starvation or rapamycin induction). After appropriate incubation periods, the level of autophagy is evaluated by detecting the formation of LC3 puncta. The results are used to verify that Autophinib can inhibit autophagy induced by both starvation and rapamycin [1] |
||
| Animal Protocol |
|
||
| References | |||
| Additional Infomation |
1. Autophinib is a novel small-molecule autophagy inhibitor with a unique aminopyrimidine chemical structure (containing pyrazole and pyrimidine structural units) [1]
2. Autophagy is a key regulator of cellular homeostasis and metabolism, and interfering with this process is considered a potential approach to treat diseases such as cancer and neurological disorders [1] 3. Autophinib exerts its autophagy-inhibiting effect by specifically targeting the lipid kinase VPS34 [1] |
| Molecular Formula |
C14H11CLN6O3
|
|
|---|---|---|
| Molecular Weight |
346.73
|
|
| Exact Mass |
346.06
|
|
| Elemental Analysis |
C, 48.50; H, 3.20; Cl, 10.22; N, 24.24; O, 13.84
|
|
| CAS # |
1644443-47-9
|
|
| Related CAS # |
|
|
| PubChem CID |
129626605
|
|
| Appearance |
Light yellow to yellow solid powder
|
|
| LogP |
3.8
|
|
| Hydrogen Bond Donor Count |
2
|
|
| Hydrogen Bond Acceptor Count |
7
|
|
| Rotatable Bond Count |
4
|
|
| Heavy Atom Count |
24
|
|
| Complexity |
431
|
|
| Defined Atom Stereocenter Count |
0
|
|
| InChi Key |
CEUMAXLRGBKFQP-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C14H11ClN6O3/c1-8-6-13(20-19-8)17-12-7-11(15)16-14(18-12)24-10-4-2-9(3-5-10)21(22)23/h2-7H,1H3,(H2,16,17,18,19,20)
|
|
| Chemical Name |
|
|
| Synonyms |
|
|
| 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)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 0.5 mg/mL (1.44 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 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 2: ≥ 0.5 mg/mL (1.44 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 5.0 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 | 2.8841 mL | 14.4204 mL | 28.8409 mL | |
| 5 mM | 0.5768 mL | 2.8841 mL | 5.7682 mL | |
| 10 mM | 0.2884 mL | 1.4420 mL | 2.8841 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA