CZ415

Catalog No.S8298

CZ415 Chemical Structure

Molecular Weight(MW): 459.56

CZ415, a potent ATP-competitive mTOR inhibitor with very good cell permeability.

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Biological Activity

Description CZ415, a potent ATP-competitive mTOR inhibitor with very good cell permeability.
Targets
mTOR [1]
(Cell-free assay)
8.07(pIC50)
In vitro

CZ415 shows no genotoxic potential and has very good cell permeability. Treatment of CZ415 leads to inhibition of phosphorylation for downstream targets of mTORC1 and mTORC2(IC50=14.5 nM for pS6RP and IC50=14.8 nM for pAKT). The immunosuppressive effect of CZ415 is measured by detecting secreted IFNγ after 18 h in stimulated human whole blood, and the resulting IC50 was 226 nM. CZ415 shows no genotoxic potential. It is neither mutagenic in a bacterial mutation assay (Ames test) nor does it show genotoxicity in the mouse lymphoma assay (MLA), in either the presence or absence of rat-liver S9 mix[1].

In vivo In vivo studies show that CZ415 has moderate clearance and good oral bioavailability. In an anti-CD3 mouse model CZ415 efficiently inhibits mTOR downstream signaling and, in a CIA mouse model, shows significant antiinflammatory effects. With its extraordinary selectivity, drug-like properties and proven efficacy in vivo, CZ415 represents an ideal molecule for the pharmacological investigation of mTOR pathophysiological role in vivo[1].

Protocol

Cell Research:[1]
+ Expand
  • Cell lines: HEK294T17 cells
  • Concentrations: 3 µM start, 8 points 1:3 dilution steps.
  • Incubation Time: 2 h
  • Method: Cells are seeded in 90 µL DMEM containing 2% FCS at 4x104 cells/well (for pS6RP S240/244 assay) or 8x104 cells/well (for pAKT S473 assay) in a 96well U-bottom plate. The plate is then incubated for 1h in a humidified incubator (37ºC, 5% CO2) to allow cells to adhere. CZ415: 3 µM start, 8 points 1:3 dilution steps, n=2. Positive control: 1 μM PI-103 (n=8). Negative control: DMSO (n=8). 10 µL of 10x compound concentration in 1% DMSO/99% (DMEM 2% FCS) are added to the cells followed by 2 h incubation in a humidified incubator (37ºC, 5% CO2). Cells are lysed by addition of 10 μL 5x Complete Lysis Buffer and gentle shaking at 4°C for 15 min
    (Only for Reference)
Animal Research:[1]
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  • Animal Models: Male SD rats
  • Formulation: 5% DMSO/95% (10% Kleptose in saline)
  • Dosages: 1 mg/kg
  • Administration: i.v.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 91 mg/mL (198.01 mM)
Water Insoluble
Ethanol Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 459.56
Formula

C22H29N5O4S

CAS No. 1429639-50-8
Storage powder
Synonyms N/A

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID