KNG-I-322

KNG-I-322 is a **desmosdumotin B derivative** that acts as a selective anticancer agent specifically targeting cancer cells that overexpress **P-glycoprotein (P-gp)**, a membrane transporter associated with multidrug resistance in cancer. It directly interacts with P-gp and selectively induces anti-proliferative and apoptotic effects in P-gp overexpressed cells (such as Hep3B/VIN), with minimal impact on P-gp-deficient cells. The mechanism involves inhibition of the **mTOR signaling pathway** (phosphorylation at mTOR Ser2448, p70S6K Thr389, and 4E-BP Thr37/46) and down-regulation of **GRP78 expression**. The anti-cancer effect is fully blocked by P-gp gene knockdown, indicating the necessity of P-gp for KNG-I-322 activity.