LADR-8

LADR-8 is a preclinical, ultra-high potency oncology drug candidate developed by CytRx Corporation and its subsidiary, Centurion BioPharma, using the Linker Activated Drug Release (LADR) platform. It is an albumin-binding prodrug consisting of an auristatin E derivative (a cytotoxic antimitotic tubulin-binding peptide) conjugated to a pH-sensitive ester linker (AE-Ester-Sulf07). Designed for intravenous administration, LADR-8 features a maleimide group that rapidly and covalently binds to the Cys34 residue of endogenous serum albumin in the blood. This allows the drug to leverage albumin as a macromolecular carrier, facilitating accumulation in tumor tissues through the enhanced permeability and retention (EPR) effect. Within the acidic environment of the tumor, the linker undergoes pH-dependent cleavage to release the auristatin payload, which inhibits tubulin polymerization and induces cell death. In human xenograft models, LADR-8 has shown significant antitumor activity against various solid tumors, including melanoma, ovarian, renal, and lung cancers, though preclinical studies noted potential skin toxicity at certain doses. The development of LADR-8 is supported by the ACDx companion diagnostic, which is intended to identify patients most likely to benefit from LADR-based therapies.

Other names

AE-Ester-Sulf07AE-Ester-Sulf-07AE-Ester-Sulf 07