SAR-405 is a potent and selective PIK3C3/Vps34 inhibitor (IC50:1.2 nM; Kd:1.5 nM) that prevents autophagy and synergizes with MTOR inhibition in tumor cells. SAR405 treatment also inhibits autophagy induced either by starvation or by MTOR (mechanistic target of rapamycin) inhibition. Combining SAR405 with everolimus results in a significant synergy on the reduction of cell proliferation using renal tumor cells.

Autophagy:, VPS34:1.2 nM, VPS34:1.5 nM (kd)

SAR405是一种低分子量的PIK3C3激酶抑制剂，它对其他脂质和蛋白激酶具有高度的选择性和效力。通过抑制PIK3C3的催化活性，SAR405可阻断从晚期内体到溶酶体的囊泡运输。无论是由于饥饿还是受到MTOR（机械性靶向性雷帕霉素）抑制，SAR405处理都能抑制自噬，阻止自噬体的形成（IC50: 42 nM）。饥饿细胞经SAR405处理后能够完全以剂量依赖的方式抑制转化为LC3-II。GFP-LC3模型用于高通量筛选(HTS)，并证实了其在饥饿细胞上的活性（IC50=419 nM）[1][2]。