P-S3iD3

P-S3iD3 is an experimental polymer-drug conjugate designed for the targeted delivery of a STAT3 inhibitor to tumor tissues. It consists of a novel small molecule STAT3 inhibitor, S3iD3, covalently attached to an N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer backbone via a pH-sensitive hydrazone bond. This linkage is stable at physiological pH but undergoes hydrolysis in the acidic environment of the tumor microenvironment or within endocytic compartments, releasing the active inhibitor. S3iD3 inhibits the Signal Transducer and Activator of Transcription 3 (STAT3) pathway, which is frequently overactivated in various cancers and contributes to chemoresistance. Preclinical studies in melanoma models have demonstrated that P-S3iD3 can effectively sensitize tumors to chemotherapy, such as HPMA-bound doxorubicin, leading to enhanced antitumor efficacy and improved survival.

Other names

HPMA-S3iD3HPMA-S-3iD3HPMA-S 3iD3HPMA copolymer-bound S3iD3