DR5/TNFRSF10B/CD262/TRAIL-R2 Drug Discovery Landscape & Assay Solutions
- By admin
- 26 Aug 2026
- Comments
Market Intelligence, Clinical Progress, and High-Purity Reagents for TRAIL-Receptor Targeted Cancer Therapy Development.
Key Molecular Characteristics
- Death Domain: Contains a functional death domain (UniProt O14763 domain), essential for DISC formation and downstream caspase activation.
- Key Mutations: Documented single-nucleotide polymorphisms in dbSNP: rs1129424 (VAR_016153), rs1047266 (VAR_016154), and rs13265018 (VAR_059831). These variations may affect receptor function and therapeutic response.
- Alternative Names: Also known as TNFRSF10B, DR5, CD262, and TRAIL-R2. Primary UniProt entry: O14763.
TarMart Solution Ecosystem & Related Targets
Comprehensive reagent toolkit for DR5/TNFRSF10B drug discovery.
| Component / Network | Product Description | Product Link |
|---|---|---|
| Antigen | TNFRSF10B (DR5) ECD-Fc Fusion Protein High purity (>95%), Endotoxin <1EU/µg, Sequence Verified. HEK293 expressed (native glycosylation). Contains complete cysteine-rich domains (CRD1-3). |
View TNFRSF10B Products |
| Gene Delivery | TNFRSF10B Promise-ORF / Lentivirus Premade Particles Full-length ORF with native signal peptide for stable cell line construction. Preserves death domain (DD) signaling integrity. |
View TNFRSF10B Products |
| Benchmark Ab | Anti-DR5 (Reference Sequences) Recombinant agonistic antibody controls (monovalent/bivalent formats available). Sequence Verified. |
View TNFRSF10B Products |
| Validator | TNFRSF10B siRNA Set (3 Unique Sequences) For knockdown verification and apoptosis rescue assays. |
View TNFRSF10B Products |
| Related Target: DR4 | TNFRSF10A (TRAIL-R1/DR4) Pro-apoptotic paralog; critical for selectivity screening and off-target analysis. |
View TNFRSF10A Products |
| Related Target: DcR1 | TNFRSF10C (TRID) Decoy receptor (GPI-anchored, no death domain); major pathway competitor for TRAIL binding. |
View TNFRSF10C Products |
| Related Target: DcR2 | TNFRSF10D (TRUNDD) Decoy receptor (truncated death domain); screening essential for agonist specificity. |
View TNFRSF10D Products |
| Related Target: FAP | Fibroblast Activation Protein TME-restricted bispecific DR5 clustering target for tumor-localized activation. |
View FAP Products |
| Critical Assay Challenge | The TarMart Advantage (Technical Spec) |
|---|---|
| Oligomerization-Dependent Activity (Clustering Requirement) | Native-conformation ECD-Fc preserves CRD domain architecture; supports tetravalent/hexavalent agonist binding studies and clustering assays. |
| Cross-species Cyno/Mouse Evaluation | Human/Cyno/Mouse TNFRSF10B ortholog proteins available with >95% purity; critical for preclinical toxicology bridging studies. |
| Selectivity vs. Death Receptor 4 (DR4) & Decoys | Homolog panel (TNFRSF10A, TNFRSF10C, TNFRSF10D) strictly verified by mass spec; enables counter-screening for true DR5-selective agonists. |
| Internalization Efficiency (ADC Development) | Lentivirus-based stable overexpression lines in HEK293 and tumor backgrounds; preserves endosomal trafficking for ADC payload delivery validation. |
| Lack of Functional Controls | Clinical benchmark antibody sequences (biosimilar) and validated siRNA included for assay specificity verification. |
Global Clinical Landscape & Future Outlook
The DR5 (TNFRSF10B) therapeutic landscape has evolved significantly following the failure of first-generation bivalent antibodies (e.g., drozitumab, conatumumab). Early bivalent antibodies failed to induce sufficient receptor clustering and suffered from hepatotoxicity due to systemic FcγR-mediated crosslinking. Current R&D focuses on multivalent agonist formats (tetravalent/hexavalent/IgM) capable of inducing the high-order clustering required for DISC formation and caspase-8 activation.
Key clinical-stage assets include:
- INBRX-109 (Inhibrx): Tetravalent DR5 agonist, Phase 1/2 in sarcoma.
- APG-880 (Apogenix): Hexavalent COMR®-based construct, targeting colorectal and gastric cancers.
- IGM-8444 (IGM Biosciences): IgM-based decavalent agonist, in solid tumors.
- APX025 (Apexigen): Bispecific DR5 x tumor antigen.
The next wave also includes ADC strategies leveraging DR5’s tumor-selective expression and internalization capacity, as well as TME-restricted bispecifics (e.g., FAP x DR5) to avoid systemic liver toxicity. Combination therapies with chemotherapy, Bcl-2 inhibitors, or checkpoint inhibitors are expected to become standard clinical development paths.
Competitive Modality & Indication Snapshot
| Modality | Representative Players | Key Indications | Critical Assay Need (Why TarMart?) |
|---|---|---|---|
| Multivalent / IgM | IGM Biosciences, Genmab | Solid Tumors, Colorectal Cancer | Clustering Assay (Need high-purity ECD-Fc & Stable Cell Lines) |
| Tetravalent Agonist | Inhibrx (INBRX-109) | Sarcoma, Solid Tumors | Cell Death Assay (Need Lentivirus stable lines for functional clustering validation) |
| Hexavalent Agonist | Apogenix (APG-880) | Colorectal, Gastric | Oligomerization Assay (Need native-conformation ECD-Fc for avidity studies) |
| Bispecific (TME-targeted) | Biotheus, Roche, Apexigen | Gastric, Pancreatic | Selectivity Panel (Need TNFRSF10A/C/D homologs for off-target screening) |
| Antibody-Drug Conjugates (ADC) | Various early-stage, Daiichi Sankyo (Legacy) | DR5-high Solid Tumors | Internalization Assay (Need high-purity ECD-Fc for binding kinetics + Lentivirus lines for trafficking) |
Live DR5/TNFRSF10B R&D Tracker
Market data changes daily. Access the latest global pipeline status directly: