Market Intelligence, Clinical Progress, and High-Purity Reagents for TP53 Y220C Mutant Solid Tumor Therapeutics Development.
The Y220C mutation in TP53 creates a unique druggable crevice on the surface of the mutant protein, enabling small-molecule stabilizers to restore wild-type function. Leading the field is PMV Pharma's PC14586 (phase II), with others like Boehringer Ingelheim, Bayer, and Cullinan Oncology advancing candidates. The next wave targets combination strategies with MDM2/MDM4 inhibitors and immune checkpoint blockers.
TarMart Solution Ecosystem & Related Targets
Comprehensive reagent toolkit for TP53 Y220C drug discovery. Select your modality below:
| Component / Network | Product Description | Product Link |
|---|---|---|
| Mutant Antigen | TP53 Y220C Mutant Recombinant Protein (DBD / Full-Length). High purity (>95%), Endotoxin <1 EU/µg. Sequence Verified. Mutation confirmed by Mass Spec. | View TP53 Y220C Products |
| WT Control | TP53 Wild-Type DBD Protein. For selectivity screening and off-target liability assessment. | View TP53 Products |
| Gene Delivery | TP53 Y220C Promise-ORF / Lentivirus. Full-length ORF for stable cell line generation. | View TP53 Y220C Products |
| Benchmark Ab | Anti-TP53 (Clone DO-1) Recombinant Antibody. Pan detection for Western/IP. Also available: Y220C-specific antibody for mutation detection. | View TP53 Y220C Products |
| Validator | TP53 siRNA Set. For knockdown verification and rescue assays. | View TP53 Products |
| Related Target A | MDM2. E3 ubiquitin ligase & p53 negative regulator; major synergy combination target. | View MDM2 Products |
| Related Target B | MDM4. Synergistic negative regulator often overexpressed in tumors. | View MDM4 Products |
| Related Target C | CDKN1A (p21). Downstream effector & pharmacodynamic marker. | View CDKN1A Products |
| Critical Assay Challenge | The TarMart Advantage (Technical Spec) |
|---|---|
| Conformational Instability & Thermal Shift Screening | High-purity monomeric Y220C protein (SEC verified, >95%) optimized for DSF/TSA. Endotoxin controlled for cell-based assays. |
| Mutant vs WT Selectivity | Matched WT and Y220C pair with >95% purity; theoretical MW verified by Mass Spec. Ideal for SPR counter-screening. |
| Lack of Controls / False Positives | Validated siRNA and clinical benchmark antibodies included for target-specificity and detection precision. |
| Structural Biology (Co-crystallization) | Monomeric purity >95% by SEC-HPLC, suitable for co-crystal structure determination. |
Live TP53 Y220C R&D Tracker
Market data changes daily. Access the latest global pipeline status directly:
- ➤ View Active Clinical Trials
- ➤ Latest Resistance Research
- ➤ Recent Patent Filings
- ➤ The Biology of Y220C Mutants
Global Clinical Landscape & Future Outlook
The race for TP53 Y220C therapeutics is intensifying, with major players shifting focus from broad p53 modulators to precision small molecule stabilizers. PC14586 (PMV Pharma) is the first-in-class mutant-selective reactivator, now in phase II for advanced solid tumors (ovarian, breast, gastric). The next wave of R&D targets resistance mutations (e.g., Y220C double mutants) and rational combinations with MDM2/MDM4 pathway inhibitors, as well as immune checkpoint blockade. PROTAC degraders are in early research phase for refractory cancers. Indicative pipeline includes Bayer, Boehringer Ingelheim, and several early-stage biotechs.
Competitive Modality & Indication Snapshot
| Modality | Representative Players | Key Indications | Critical Assay Need (Why TarMart?) |
|---|---|---|---|
| Small Molecule Stabilizer | PMV Pharma, Boehringer Ingelheim, Bayer | Advanced Solid Tumors (Ovarian, Breast, Gastric, NSCLC, CRC) | Thermal Shift Assay (need high-purity monomeric Y220C protein) |
| PROTAC / Degrader | Early-stage Biotech | Refractory Cancers (Solid & Hematologic) | Degradation Assays (need mutant cell lines via lentivirus) |
| Combination Therapy (MDM2/PD-1) | Various (with MDM2/MDM4 inhibitors) | Refractory Solid Tumors | Pathway Analysis (need pathway-related proteins: MDM2, MDM4, p21) |
Key Scientific Context from Fact Payload
The Y220C mutation is a somatic hotspot in sporadic cancers. It abolishes phosphorylation at a key site, reduces interaction with ZNF385A, and is listed in dbSNP as rs587782646. These features underscore the importance of selective stabilization to restore p53 function without affecting wild-type.