AIM-100 is a potent and selective Ack1 (TNK2) inhibitor with IC50 value of 22nM, showing suppression phosphorylation of Tyr267 of theandrogen 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]
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