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CreTAC-1

Development stage: Preclinical
Modality: PROTACs (E3 ligase recruitment) → Targeted Protein Degraders (TPDs) → Small Molecules, Biodegradable Polymers → Polymer-based Nanoparticles → Nanoparticles → Drug Delivery Systems, Bivalent/Multivalent Binders → Multivalent & Scaffold-Based Small Molecules → Small Molecules
Administration: Intravenous

Overview

CreTAC-1 is a charge-reversal proteolysis-targeting chimera (CreTAC) designed for the tissue-specific degradation of the Stimulator of Interferon Genes (STING) protein. It is engineered using a pH-responsive polymer platform that maintains electroneutrality at physiological pH (7.4) to minimize systemic toxicity but undergoes protonation and charge inversion in the acidic microenvironment of rheumatoid arthritis joints (pH ~6.5). This transition facilitates a significant increase in joint accumulation, cellular uptake, and cytoplasmic affinity for STING. By promoting the degradation of STING variants, CreTAC-1 effectively suppresses synovitis and bone erosion in preclinical models of collagen-induced arthritis without the hematological toxicity associated with conventional treatments like methotrexate.

Other names: charge-reversal proteolysis-targeting chimera 1

Targets

STING (Stimulator of interferon genes protein)

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