Novel camptothecin analogs as second generation camptothecin drugs emphasize on modification on E-ring with a group which not only stabilizes the active site but also functions as a strong radio-sensitizer to overcome radio- and chemo-resistance that is frequently encountered in clinical therapies, enabling Lipotecan® to tailor at unmet needs. Lipotecan® has been granted orphan drug status by US FDA and EU EMEA for the treatment of hepatocellular carcinoma (HCC).