AIM-100 is a potent and selective Ack1 (TNK2) inhibitor with IC50 value of 22nM, showing suppression phosphorylation of Tyr267 of the androgen receptor in prostate cancer cells.
AIM-100 is an Ack1 inhibitor. It inhibited EGF induced Ack1 activation on Tyr284 site at concentration of 0.8μM for 16h in serum-depleted MEFs, and suppressed EGF induced pTyr267-AR phosphorylation in serum and androgen-depleted LAPC4 cells. Treatment with 0.8μM AIM-100 for 16h inhibited pTyr267-AR binding to AREs, binding of AR to PSA, NKX3.1, and TMPRSS2 promoters in serum and androgen depleted LAPC4 cells and suppressed androgen-independent pTyr267-AR transcriptional activity and PSA gene expression[4]. AIM-100 suppressed Ack1 mediated ATM expression and mitigated the growth of radioresistant CRPC (castration-resistant prostate cancer) tumors[5]. AIM-100 promoted dramatic oligomerization, clustering and CIE (Clathrin-independent endocytosis) of human and mouse dopamine transporters (DAT), through an allosteric mechanism associated with the DAT conformational state[6].
作用机制
AIM-100 inhibits pTyr267-AR binding to AREs, binding of AR to PSA, NKX3.1, and TMPRSS2 promoters.[4]
AIM-100 细胞实验
Cell Line
Concentration
Treated Time
Description
References
A2780-CP cells
0.8 µM
overnight
Inhibited Ack1 activation and AKT tyrosine phosphorylation
Am J Pathol. 2012 Apr;180(4):1386-93
LNCaP cells
5 μM
24 h
To evaluate the effect of AIM-100 on IR-induced G2/M checkpoint
J Biol Chem. 2012 Jun 22;287(26):22112-22
PAE/YFP-DAT cells
20 μM
2 h
AIM-100 promotes DAT oligomerization
Elife. 2018 Apr 9;7:e32293
SH-SY5Y cells
20 μM
2 h
AIM-100 induces endocytosis of YFP-HA-DAT
Elife. 2018 Apr 9;7:e32293
HEK293 cells
20 μM
2 h
AIM-100 induces endocytosis of DAT
Elife. 2018 Apr 9;7:e32293
Porcine aortic endothelial (PAE) cells
20 μM
2 h
To investigate the effect of AIM-100 on DAT oligomerization and endocytosis
Neuropharmacology. 2019 Dec 15;161:107676
PAE/YFP-HA-DAT cells
20 μM
90 min
AIM-100 promotes redistribution of YFP-HA-DAT from the plasma membrane to intracellular vesicular compartments
Elife. 2018 Apr 9;7:e32293
A549 cells
20 μM
48 h
Evaluate the effect of AIM-100 on proliferation in lung cancer cells, results showed AIM-100 significantly inhibited proliferation of A549 cells.
Mol Med. 2023 Jan 16;29(1):6
A549 cells
20 μM
24 h
Evaluate the effect of AIM-100 on apoptosis in lung cancer cells, results showed AIM-100 significantly promoted apoptosis of A549 cells.
Mol Med. 2023 Jan 16;29(1):6
A549 cells
20 μM
12 h
Evaluate the effect of AIM-100 on autophagy-like response in lung cancer cells, results showed AIM-100 induced autophagy-like response.
Mol Med. 2023 Jan 16;29(1):6
Bone marrow-derived dendritic cells (BMDCs)
5, 10, 20 µM
2 h
Inhibition of ACK1 activity significantly attenuated LPS-, R848-, or CpG-1826-induced CD86 and CD40 expression, as well as IL-12 and TNF-α secretion.
Front Immunol. 2022 May 20;13:864995
T47D cells
10 µM
48 h
Inhibition of ACK1 kinase activity, significantly reduced HOXA1 gene expression, and inhibited cell proliferation.
J Biol Chem. 2014 Oct 10;289(41):28179-91
LAPC4 cells
1 μM
16 h
To evaluate the inhibitory effect of AIM-100 on Ack1-mediated AR Tyr267 phosphorylation
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