Vismodegib is an oral and high selective hedgehog (Hh) inhibitor used for the treatment of basal cell carcinoma (BCC). In this work, analogs of Vismodegib with deuterium-for-hydrogen replacement at certain metabolically active sites were prepared and found to have a better pharmacokinetic properties in mice. In particular, deuterated compound SKLB-C2211 obviously altered the blood circulation behavior compared to its prototype, which was demonstrated by significantly prolonged blood circulation half-life time (t_1/2) and increased AUC_0→∞. These results suggested SKLB-C2211 had the potential to be a long-acting inhibitor against Hh signaling pathway, and laid the foundation for the further research of its druggability.

Vismodegib是一种口服和高选择性刺猬（Hh）抑制剂，用于治疗基底细胞癌（BCC）。在这项工作中，制备了在某些代谢活性位点上具有氘代氢取代作用的Vismodegib类似物，并发现其在小鼠中具有更好的药代动力学特性。特别是，氘代化合物SKLB-C2211与原型相比明显改变了血液循环行为，这可以通过明显延长血液循环半衰期（t _1/2）和增加AUC _0→∞来证明。这些结果表明SKLB-C2211有可能成为Hh信号通路的长效抑制剂，并为进一步研究其可药用性奠定了基础。