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actinium-225-macropa-polyethylene glycol-4-YS5-monomethyl auristatin E
- Development stage
- Preclinical
- Lead developer
- University of California, San Francisco
- Modality
- Antibody-Radionuclide Conjugates → Antibody Conjugates → Antibody-Based Therapeutics, Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics
- Administration
- Parenteral
01
Overview
**Actinium-225-macropa-polyethylene glycol-4-YS5-monomethyl auristatin E** is an investigational CD46-directed dual-payload radioimmunoconjugate developed by University of California researchers for prostate cancer and multiple myeloma. The single covalent construct incorporates the CD46-targeting YS5 antibody, a Macropa-PEG4 chelator complexed with the alpha-emitting radionuclide actinium-225, and the microtubule-disrupting cytotoxic payload monomethyl auristatin E delivered through an mc-vc-pab linker. CD46-mediated tumor targeting enables localized alpha-particle irradiation and intracellular delivery of monomethyl auristatin E, producing DNA damage and mitotic disruption. In preclinical prostate cancer models, the dual-labeled construct produced durable tumor regression and improved survival relative to either CD46-targeted alpha therapy or the YS5-monomethyl auristatin E antibody-drug conjugate alone.
- Other names
- 225Ac-Macropa-PEG4-YS5-MMAE[225Ac]-Macropa-PEG4-YS5-MMAE[225Ac]Macropa-PEG4-YS5-MMAEactinium-225-macropa-polyethylene glycol-4-YS5-monomethyl auristatin Eactinium225-macropa-polyethylene glycol-4-YS5-monomethyl auristatin Eactinium 225-macropa-polyethylene glycol-4-YS5-monomethyl auristatin ER-ADC
02
Targets
TUBB (Tubulin (alpha and beta subunits))CD46 (CD46 Molecule)DNA
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