Amphethinile, an anti-tubulin agent, has a Ka with tubulin of 1.3 μM.

Tubulin: 1.3 μM (Ka)

Amphethinile exhibits strong binding affinity to microtubule proteins (Ka=1.3 µM) and effectively inhibits the assembly of tubulin without promoting its rapid disassembly. Its inhibitory concentration for assembly (12 μM) closely matches that of colchicine (11 μM), and it competes for the same binding sites as colchicine, though not for those targeted by vinca alkaloids. Furthermore, amphethinile enhances the GTPase activity of tubulin, akin to the effects observed with combretastatin A4 and 2-methoxy-5-(2',3',4'-trimethoxyphenyl) tropolone (MTPT). It causes a G2/M phase block in the cell cycle and demonstrates equal toxicity towards both parental and daunorubicin-resistant P388 cells. Unlike daunorubicin, vincristine, and vinblastine, where resistance in P388 cells is linked to reduced drug accumulation, amphethinile's effectiveness is less affected by such resistance mechanisms.

Pharmacokinetic studies in male mice reveal an AUC of 313 μg/L per hour at doses equivalent to the LD10. Following a bolus intravenous injection, the alpha half-life is 8 minutes, and the beta half-life is 100 minutes, which is relatively independent of the dose level [2].