AD80

Catalog No.S8518 Batch:S851801

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Technical Data

Formula

C22H19F4N7O
Molecular Weight 473.43 CAS No. 1384071-99-1
Solubility (25°C)* In vitro DMSO 94 mg/mL (198.55 mM)
Ethanol 94 mg/mL (198.55 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
2%DMSO 30%PEG300 2%Tween80 66%ddH2O
4.0mg/ml Taking the 1 mL working solution as an example, add 20 μL of 200 mg/ml clarified DMSO stock solution to 300 μL of PEG300, mix evenly to clarify it; add 20 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 660 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description AD80, a multikinase inhibitor, shows strong activity against human RET (c-RET), BRAF, S6K, and SRC but were much less active than either AD57 or AD58 against mTOR. The IC50 value for RET is 4 nM.
Targets
Raf [2]
(Cell-free)		 Src [2]
(Cell-free)		 S6 Kinase [2]
(Cell-free)		 RET V804M [1]
(Cell-free assay)		 RET V804L [1]
(Cell-free assay)		 View More
0.4 nM 0.6 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 AD80 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, AD80 and AD81 inhibit RET, RAF, SRC and S6K, with greatly reduced mTOR activity relative to AD57 and AD58. AD80 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. AD80 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 AD80 (25 mg/kg) is observed but not in tumors treated with cabozantinib or vandetanib[1].

Protocol (from reference)

Cell Assay:

[1]
  • Cell lines

    LC-2/AD cells

  • Concentrations

    0, 10, or 100 nM

  • Incubation Time

    4 h

  • Method

    Immunoblotting is performed in LC-2/AD cells treated with AD80, cabozantinib, or vandetanib (4 hours).
Animal Study:

[1]
  • Animal Models

    NSG mice

  • Dosages

    12.5 to 25 mg/kg 

  • Administration

    oral gavage

Selleck's AD80 has been cited by 8 publications

Distinctive molecular features of regenerative stem cells in the damaged male germline [ Nat Commun, 2022, 13(1):2500] PubMed: 35523793
Targeting RET Kinase in Neuroendocrine Prostate Cancer [ Mol Cancer Res, 2020, 18(8):1176-1188] PubMed: 32461304
Elucidating the Mechanism of RET Kinase Activity in Neuroendocrine Prostate Cancer [ Mol Cancer Res, 2020, 1176-1188] PubMed: None
Targeting RET Kinase in Neuroendocrine Prostate Cancer [ Mol Cancer Res, 2020, 27;molcanres.1245.2019] PubMed: 32461304
Neurturin regulates the lung-resident macrophage inflammatory response to viral infection [ Life Sci Alliance, 2020, 3(12)e202000780] PubMed: 33020210
RET Kinase Signaling as a Key Switch Toward the Neuroendocrine Phenotype [ Defense Technical Information Center, 2020, N/A] PubMed: N/A
Multi-kinase targeted therapy as a promising treatment strategy for ovarian tumors expressing sfRon receptor [ Genes Cancer, 2020, 11(3-4):106-121] PubMed: 33488949
[ Cell Rep, 2017, ] PubMed: 28877471

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.