First-in-class mitochondrial-targeting degradation drug development platform clearing damaged mitochondria via induced mitophagy.
Contact Us
Platform Overview
Current therapeutic approaches struggle to address diseases driven by mitochondrial dysfunction – damaged mitochondria accumulate, producing ROS, mtDNA mutations, and inflammatory signals that accelerate aging and neurodegeneration. Traditional PROTACs degrade individual proteins but cannot clear entire organelles. Protheragen introduces MitoClear™ – a groundbreaking mitochondrial-targeting degradation platform inspired by PROTAC design. Our bifunctional chimeric molecules recruit E3 ubiquitin ligases to the outer mitochondrial membrane (OMM), triggering K63-linked ubiquitination and subsequent mitophagy. This enables efficient clearance of damaged mitochondria, offering a novel therapeutic strategy for aging, neurodegenerative diseases, and mitochondria-related disorders.
Disruptive Technology
Excellent Team
Diversified Pipeline
Customized Solutions
Platform Core
The MitoClear™ platform is built upon a novel bifunctional chimeric molecule design that recruits E3 ubiquitin ligases to damaged mitochondria, triggering K63-linked ubiquitination and subsequent mitophagy. Unlike traditional PROTACs that degrade individual proteins via the proteasome, MitoClear™ clears entire dysfunctional organelles. Three integrated technologies form the foundation of this platform:
Precision Design of Bifunctional Chimeric Molecules
Each MitoClear™ molecule consists of three functional modules: a TSPO-targeting ligand that binds specifically to the outer mitochondrial membrane, an E3 ligase ligand (e.g., CRBN or VHL) that recruits ubiquitination machinery, and an optimized linker that tunes flexibility, solubility, and membrane permeability. This modular design ensures efficient ternary complex formation and potent mitophagy induction.
Non-Canonical Ubiquitination & Mitophagy Activation Mechanism
Upon recruitment of E3 ligases to the outer mitochondrial membrane, MitoClear™ catalyzes K63-linked ubiquitination of OMM proteins such as TSPO and MFN2 – distinct from the K48-linked ubiquitination that targets proteins for proteasomal degradation. These K63 ubiquitin chains act as "mitophagy tags," recruiting autophagy receptors including LC3 and p62 to form autophagosomes that fuse with lysosomes for mitochondrial clearance.
TSPO-Targeted Mitochondrial Localization Technology
TSPO (translocator protein) is a transmembrane protein specifically upregulated on damaged mitochondria and highly expressed in high-energy tissues such as brain, heart, and liver. Based on TSPO crystal structure, we have screened high-affinity, highly selective small molecule ligands that ensure precise mitochondrial anchoring. This targeting strategy directs MitoClear™ exclusively to dysfunctional mitochondria without affecting healthy organelles.
Platform Advantages
First-in-Class Mitochondrial Degradation Technology
The first platform combining PROTAC-inspired bifunctional design with mitophagy mechanism. Unlike traditional PROTACs that degrade single proteins, MitoClear™ clears entire damaged organelles – addressing a critical technology gap in mitochondrial dysfunction.
Efficient Clearance of Damaged Mitochondria
Induces K63-linked ubiquitination to trigger mitophagy, specifically removing dysfunctional mitochondria. Reduces ROS accumulation, mtDNA mutations, and inflammatory activation – restoring cellular homeostasis and slowing disease progression.
High Safety, Low Off-Target Risk
TSPO-specific targeting ensures localization only to mitochondria, avoiding interference with normal proteins or organelles. Non-proteasomal mechanism bypasses toxicity and resistance issues associated with proteasome inhibitors. Selectively clears damaged mitochondria while preserving healthy ones.
Excellent Druggability & Broad Applicability
Small molecule chimeras offer good oral bioavailability, metabolic stability, and blood-brain barrier penetration – ideal for CNS disorders. Modular design allows rapid exchange of E3 ligands or TSPO binders to optimize activity and PK properties across different disease contexts.
Platform Application
Clears damaged mitochondria in senescent cells, reducing ROS and DNA damage to delay aging and extend healthspan. Applicable to Alzheimer's disease (reducing Tau phosphorylation and Aβ deposition) and Parkinson's disease (clearing damaged mitochondria in dopaminergic neurons).
Removes dysfunctional mitochondria in ALS (protecting motor neurons) and Huntington's disease (reducing mutant huntingtin-associated mitochondrial toxicity). Offers a disease-modifying approach beyond symptomatic treatment.
Addresses primary mitochondrial disorders (e.g., MELAS syndrome, mitochondrial myopathy) by clearing mutation-laden mitochondria. Also applicable to secondary mitochondrial dysfunction in diabetic cardiomyopathy, NASH, and cardiovascular disease.
Combines with chemotherapy or radiotherapy to selectively clear therapy-resistant abnormal mitochondria in tumor cells, thereby overcoming drug resistance, enhancing treatment efficacy, and improving long-term patient outcomes.
Clears damaged mitochondria in immune cells to inhibit NLRP3 inflammasome activation and downstream inflammatory cascades – applicable to rheumatoid arthritis, lupus, inflammatory bowel disease, and other chronic inflammatory conditions.
Pipeline
| Projects | Mode | Indication | Discovery | Preclinical | IND | Phase I | Phase II | Phase III |
|---|---|---|---|---|---|---|---|---|
| MTC009 | TSPO – CRBN Bifunctional Chimera | Parkinson's Disease | ||||||
| MTC015 | TSPO – VHL Bifunctional Chimera | Alzheimer's Disease | ||||||
| MTC024 | TSPO – CRBN Bifunctional Chimera | Solid Tumors (Combination Therapy) | ||||||
Contact Us
FAQs
Q1: How is MitoClear™ different from traditional PROTACs?
Q2: What is TSPO and why target it?
Q3: Does MitoClear™ affect healthy mitochondria?
Q4: What is the mechanism of mitophagy induction?
Q5: Can MitoClear™ cross the blood-brain barrier?
MitoClear™ is a first-in-class mitochondrial-targeting degradation platform that clears damaged mitochondria via induced mitophagy to empower next-generation therapeutics for aging, neurodegeneration, and inflammatory diseases.
Copyright © 2026 Protheragen. All rights reserves.