Home Protein Tyrosine Kinase c-RET inhibitor - Src inhibitor - S6 Kinase inhibitor AD80

research use only

AD80 c-RET inhibitor

Cat.No.S8518

AD80, a multikinase inhibitor, shows strong activity against human RET (c-RET), BRAF, S6K, and SRC but was much less active than either AD57 or AD58 against mTOR. The IC50 value for RET is 4 nM.
AD80 c-RET inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 473.43

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: S851801 DMSO]94 mg/mL]false]Ethanol]94 mg/mL]false]Water]Insoluble]false Purity: 99.85%
99.85

Chemical Information, Storage & Stability

Molecular Weight 473.43 Formula

C22H19F4N7O

 Storage (From the date of receipt)
CAS No. 1384071-99-1 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles CC(C)N1C2=NC=NC(=C2C(=N1)C3=CC=C(C=C3)NC(=O)NC4=C(C=CC(=C4)C(F)(F)F)F)N

Solubility

In vitro
Batch:

DMSO : 94 mg/mL (198.55 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 94 mg/mL

Water : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
Batch:

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC50/Ki
Raf [2]
(Cell-free)
Src [2]
(Cell-free)
S6 Kinase [2]
(Cell-free)
RET V804M [1]
(Cell-free assay)
0.4 nM
RET V804L [1]
(Cell-free assay)
0.6 nM
RET wt [1]
(Cell-free assay)
1.3 nM
In vitro
AD80 prevents the phosphorylation of RET as well as of extracellular signa-regulated kinase (ERK), AKT, and S6K at low nanomolar concentrations in kinesin family member 5B (KIF5B)-RET-expressing Ba/F3 cells. Treatment with this compound results in up-regulation of genes that are typically repressed by active KRAS. On the contrary, genes that are activated by KRAS were down-regulated[1]. On the basis of in vitro human kinase profiles, this chemical and AD81 inhibit RET, RAF, SRC and S6K, with greatly reduced mTOR activity relative to AD57 and AD58. It inhibits proliferation of MZ-CRC-1 and TT thyroid cancer cells in culture, probably through the induction of apoptosis[2].
In vivo
AD80 is a highly potent RET inhibitor with a favorable pharmacokinetic profile in clinically relevant RET fusion-driven tumor models. This compound potently shrinks RET-rearranged tumors in patient-derived xenografts. A pronounced reduction in phosphorylation of RET as well as AKT and ERK in tumors treated with this chemical (25 mg/kg) is observed but not in tumors treated with cabozantinib or vandetanib[1].
References

Applications

Methods Biomarkers Images PMID
Western blot p-RET / RET / p-AKT / AKT / p-ERK / ERK / p-S6 / S6 S8518-WB1 28615362

Tech Support

Handling Instructions

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

If you have any other enquiries, please leave a message.

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.

Signaling Pathway Map