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APR-246 + carboplatin + pegylated liposomal doxorubicin
- Development stage
- Phase 2
- Lead developer
- Aprea Therapeutics
- Modality
- Classical Binding Small Molecules → Small Molecules, Covalent Small Molecules → Small Molecules, Nucleic Acid-Directed Small Molecules → Small Molecules, Nanoparticles → Drug Delivery Systems
- Administration
- Intravenous
01
Overview
APR-246 + carboplatin + pegylated liposomal doxorubicin is a **combination therapy** under investigation for the treatment of cancer, especially TP53-mutant and platinum-resistant malignancies. - **APR-246** (also known as PRIMA-1MET) is a small molecule prodrug converted intracellularly to methylene quinuclidinone (MQ), which binds mutant TP53 and restores its wild-type conformation and transcriptional activity. This compound also induces various forms of programmed cell death, including apoptosis, necroptosis, and ferroptosis, and may act independently of TP53 mutation status[1][5]. - **Carboplatin** is a platinum-based DNA-alkylating agent that induces crosslinks in DNA, leading to apoptosis. - **Pegylated liposomal doxorubicin** (branded as Caelyx) is an anthracycline chemotherapeutic encapsulated within pegylated liposomes, enhancing tumor selectivity and reducing off-target toxicity. Doxorubicin itself intercalates DNA, inhibits topoisomerase 2, and generates free radicals that damage cellular macromolecules[2][4][8]. This combination regimen aims to induce cytotoxicity through complementary mechanisms: restoration of TP53 activity, direct DNA damage, and inhibition of DNA repair and replication.
- Other names
- carboplatinpegylated liposomal doxorubicindoxorubicin hydrochloride liposomePRIMA-1METPRIMA1METPRIMA 1MET
02
Targets
DNAGSH (Glutathione)TP53 (Cellular Tumor Antigen p53 R175H)TOP2A (DNA topoisomerase II)
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