Subtitle: Market Intelligence, Clinical Progress, and High-Purity Reagents for Th2 Inflammatory Disease Development.
Target Overview: IL-1RL1 (ST2) Biology and Key Features
IL-1RL1, commonly known as ST2, is the specific receptor for IL-33 and a critical mediator of Th2-type inflammation. The mature protein comprises three Ig-like C2-type domains (Ig-like C2-type 1, 2, 3) that constitute the extracellular region (ECD) essential for IL-33 binding and subsequent signal transduction via the co-receptor IL-1RAcP. Key single nucleotide polymorphisms (SNPs) have been documented in the IL1RL1 gene, including rs1041973, rs4988956, and rs10192036, which may influence receptor expression or function and are associated with asthma susceptibility. Understanding these features is crucial for designing selective and effective therapeutic agents.
TarMart Solution Ecosystem & Related Targets
Comprehensive reagent toolkit for IL-1RL1 (ST2) drug discovery. Select your modality below:
| Component / Network | Product Description | Product Link |
|---|---|---|
| Antigen | IL-1RL1 (ST2) ECD-Fc Fusion Protein High purity (>95%), Endotoxin <1EU/ug. Sequence Verified. HEK293 Expressed (Native Glycosylation). |
View IL-1RL1 Products |
| Ligand | IL-33 Recombinant Protein Full-length mature domain. Bioactive conformation for binding assays. |
View IL33 Products |
| Gene Delivery | IL-1RL1 Lentivirus Particles Full-length ORF for stable Ba/F3 or CHO cell line construction. Puromycin selection. |
View IL-1RL1 Products |
| Benchmark Ab | Anti-IL-1RL1 Reference Antibody (Sequence of Astegolimab) Recombinant positive control for blocking assay development. |
View IL-1RL1 Products |
| Validator | IL-1RL1 siRNA Set Validated sequences for target specificity confirmation and knockdown verification. |
View IL-1RL1 Products |
| Related Target A | IL-33 Primary ligand. Essential for competitive binding assays. |
View IL33 Products |
| Related Target B | IL-1RAcP (IL1R3) Co-receptor required for IL-33/IL-1RL1 signal transduction. Critical for ternary complex studies. |
View IL1RAcP Products |
| Related Target C | IL1R1 (IL-1 Receptor Type 1) Subfamily member for selectivity screening. |
View IL1R1 Products |
| Related Target D | IL1RL2 (IL-36 Receptor) Family homology comparison for off-target evaluation. |
View IL1RL2 Products |
Critical Assay Challenges & The TarMart Advantage
| Critical Assay Challenge | The TarMart Advantage (Technical Spec) |
|---|---|
| Cross-species cyno/mouse eval | Human/Mouse/Cynomolgus IL-1RL1 ECD-Fc proteins available with >95% purity; Sequence verified by Mass Spec |
| IL-1 Family selectivity screening | Homolog panel including IL1R1, IL1RL2, IL1R3 strictly verified by mass spec; Endotoxin controlled |
| Glycosylation-dependent ligand binding | HEK293 Expression ensures native mammalian glycosylation patterns necessary for accurate IL-33 interactions |
| Soluble vs Membrane isoform discrimination | Full-length Lentivirus for membrane presentation; ECD-Fc for soluble decoy mechanism studies |
| Lack of Controls | Clinical Benchmark Antibodies (Biosimilars) included for assay standardization |
| False Positives | Validated siRNA included for specificity checks in cell-based assays |
Live IL-1RL1 (ST2) R&D Tracker
Market data changes daily. Access the latest global pipeline status directly:
Global Clinical Landscape & Future Outlook
The race for IL-1RL1 (ST2) therapeutics is intensifying, with major players shifting focus from traditional anti-IL-5 biologics to IL-33/ST2 axis modulation for treatment-resistant asthma and fibrotic diseases. As first-generation anti-ST2 antibodies (Astegolimab from Roche/Genentech) advance through Phase 3 (NCT05131438) for severe asthma and COPD, the next wave of R&D is targeting combination strategies with TSLP/IL-13 pathways and soluble ST2 (sST2) biomarker-guided patient stratification. GSK’s Melrilimab and Sanofi’s IL-33-targeting agents represent additional competitive forces.
Cardiovascular applications represent a parallel growth vector, with sST2 serving as a validated biomarker in heart failure and emerging evidence supporting direct ST2 inhibition in cardiac remodeling. The differentiation battleground now centers on epitope selection—whether to block IL-33 binding exclusively or to induce receptor internalization—and the pharmacokinetic optimization for subcutaneous delivery in chronic respiratory indications. Extended half-life formulations (e.g., YTE mutations) enabling monthly or longer dosing intervals are becoming a core competitive advantage.
Competitive Modality & Indication Snapshot
Connect market trends to assay needs.
| Modality | Representative Players | Key Indications | Critical Assay Need (Why TarMart?) |
|---|---|---|---|
| Blocking mAb | Roche/Genentech (Astegolimab), Novartis, GSK | Severe Asthma, COPD, Atopic Dermatitis | IL-33 Competition ELISA (Need high-affinity ECD-Fc) |
| Soluble Receptor Trap | Preclinical Biotech | Fibrosis, Heart Failure | Sustained Release Assay (Need stable IL-1RL1-Fc fusion) |
| Bispecific | Emerging Startups | Severe Refractory Asthma, Atopic Dermatitis | Heterodimer Validation (Need Cross-reactive Abs & Co-receptors like IL-1RAcP) |
| Small Molecule Inhibitor | Academic/Discovery | Oral Asthma Therapy, Systemic Inflammation | Orthosteric vs Allosteric Screening (Need full-length Membrane Protein) |
Molecular Differentiation & Assay Strategy
Successful drug candidates targeting ST2 must differentiate on several key parameters:
- Affinity: High (pM range) affinity is required to compete with local IL-33 concentrations. Use SPR/BLI with HEK293-expressed ECD-Fc for accurate kinetics.
- Internalization: For ADC or receptor down-modulation strategies, internalization efficiency needs to be assessed using full-length ST2 lentivirus stable cell lines (e.g., Ba/F3-ST2) in flow cytometry internalization assays.
- Epitope Specificity: Avoid epitopes that interfere with IL-1RAcP recruitment (risk of off-target IL-1 signaling). Use IL-1RAcP recombinant protein in ternary complex competition ELISA.
- Selectivity: Ensure >100-fold selectivity over IL-1R1, IL-1RL2, and other IL-1 receptor family members. Use FACS cross-reactivity panels with stable cell lines.
- Soluble vs Membrane: Distinguish between neutralizing circulating IL-33 (via sST2 decoy) versus blocking membrane ST2 signaling. Compare binding affinities to full-length membrane protein (lentivirus) and soluble ECD-Fc.
TarMart provides the essential tools for each of these differentiations, including cross-species orthologs, mutant proteins for epitope binning, and validated positive controls.
Related Targets and Cross-Selling Opportunities
- IL-33: Primary ligand; required for binding and functional assays.
- IL-1RAcP (IL1R3): Co-receptor for signal transduction; essential for compound screening blocking ternary complex assembly.
- TSLPR/CRLF2: Th2 pathway synergy; used for developing bispecific antibodies or co-culture assays.
- IL-4Rα / IL-13Rα1: Downstream signaling nodes; for investigating crosstalk between ST2 and IL-4/IL-13 axes.