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AD80

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Chemical Structure| 1384071-99-1 同义名 : -
CAS号 : 1384071-99-1
货号 : A712840
分子式 : C22H19F4N7O
纯度 : 99+%
分子量 : 473.426
MDL号 : MFCD31382193
存储条件：

粉末 Inert atmosphere,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(105.61 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+30% PEG300+water 0.5 mg/mL clear

PO 0.5% CMC-Na 45 mg/mL suspension

生物活性
靶点

  • c-RET

    RET wt, IC50:1.3 nM

    RET V804M, IC50:0.6 nM
描述 AD80 is a multikinase inhibitor targeting on RET, RAF, SRC and S6K, eliminated its binding with TOR. Oral administration of AD80 resulted in a notable 70–90% of animals developing to adulthood in our Drosophila ptc>dRetMEN2B model. It restored Src and Ras activities by the ectopic Src activation and thus strongly suppressed wing vein pattern phenotypes. AD80 inhibited proliferation of MZ-CRC-1 and TT thyroid cancer cells in culture, probably through the induction of apoptosis, with potent downregulation of phosphorylated Ret and several downstream biomarkers. AD80 also promoted enhanced tumour growth inhibition and reduced body-weight modulation relative to vandetanib in a mouse xenograft model. AD80 showed high activity in RET kinase gatekeeper mutant cells, Ba/F3 cells expressing KIF5B-RETV804M or CCDC6-RETV804M and inhibited phosphorylation of RET as well as of ERK, AKT, and S6K in these cells.
作用机制 AD80 specifically targets RET and tightly binds to RET fusion kinase, effectively inhibiting RET kinase in DFG-out conformation.[1]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.11mL

0.42mL

0.21mL

10.56mL

2.11mL

1.06mL

21.12mL

4.22mL

2.11mL
参考文献

[1]Dar AC, Das TK, et al. Chemical genetic discovery of targets and anti-targets for cancer polypharmacology. Nature. 2012 Jun 6;486(7401):80-4.

[2]Plenker D, Riedel M, et al. Drugging the catalytically inactive state of RET kinase in RET-rearranged tumors. Sci Transl Med. 2017 Jun 14;9(394). pii: eaah6144.