Market Intelligence, Clinical Progress, and High-Purity Reagents for Oxidative Stress, Inflammation, and Oncology Development.
TarMart Solution Ecosystem & Related Targets
Comprehensive reagent toolkit for KEAP1 cysteine-targeting drug discovery. Select your modality below:
| Component / Network | Product Description | Product Link |
|---|---|---|
| Antigen (WT) | KEAP1 Full-Length Recombinant Protein. High purity (>95%), Endotoxin <1 EU/μg. Native cysteine residues (C151, C273, C288) intact for electrophile reactivity studies. Sequence Verified. | View KEAP1 Cysteines Products |
| Antigen (Mutant) | KEAP1 Cysteine Mutant Panel (C151S, C273S, C288S, C434S, C489S, C583S, C624S). Single-point mutations for covalent binding site mapping. HEK293 expressed. | View KEAP1 Cysteines Products |
| Gene Delivery | KEAP1 Promise-ORF / Lentivirus. Full-length ORF for stable cell lines. | View KEAP1 Cysteines Products |
| Benchmark Ab | Anti-KEAP1 Recombinant Antibody. Sequence of commercial diagnostic standard, positive control for Western/IP. | View KEAP1 Cysteines Products |
| Validator | KEAP1 siRNA Set. For knockdown verification in secondary assays. | View KEAP1 Cysteines Products |
| Binding Partner (NRF2) | NRF2 (NFE2L2) Kelch Domain Protein. High-affinity ETGE motif containing fragment for competitive binding assays. | View NFE2L2 Products |
| E3 Complex Component (CUL3) | CUL3 Recombinant Protein. Scaffold for KEAP1 E3 ubiquitin ligase complex reconstitution. | View CUL3 Products |
| E3 Complex Component (RBX1) | RBX1 (ROC1) Recombinant Protein. RING domain essential for KEAP1-mediated ubiquitination. | View RBX1 Products |
Critical Assay Challenges & The TarMart Advantage
| Critical Assay Challenge | TarMart Advantage (Technical Spec) |
|---|---|
| Covalent Cysteine Selectivity Mapping | Complete cysteine mutant panel (C151S, C273S, C288S, C434S, C489S, C583S, C624S) with >95% purity, mass spectrometry verified. |
| KEAP1-NRF2 Disruption Quantification | High-purity WT KEAP1 Kelch domain and NRF2 ETGE peptide for FP/TR-FRET competitive binding assays. |
| Covalent Adduct Confirmation | Endotoxin controlled (<1 EU/μg) to prevent oxidative artifacts. Suitable for intact mass spectrometry. |
| Ubiquitination Cascade Reconstitution | CUL3 and RBX1 co-expressed components available for full E3 ligase complex assembly. |
| False Positive Control | Validated siRNA included for KEAP1 knockdown specificity verification. |
| Lack of Cellular Models | Lentivirus premade particles for rapid stable ARE-reporter or KEAP1 cell line construction. |
Live KEAP1 Cysteines R&D Tracker
Market data changes daily. Access the latest global pipeline status directly:
Global Clinical Landscape & Future Outlook
The race for therapeutics targeting KEAP1 Cysteines is intensifying. Major players are shifting focus from pan-reactive electrophiles like bardoxolone methyl (Reata Pharmaceuticals) and dimethyl fumarate (Biogen) to highly selective C151-targeted covalent inhibitors. First-generation NRF2 activators have demonstrated efficacy in chronic kidney disease (Alport syndrome), Friedreich's ataxia, and multiple sclerosis, but face safety challenges due to non-specific cysteine modifications. The next wave of R&D targets specific cysteine subsets (particularly C151 vs C273/C288) to dissociate therapeutic antioxidant effects from off-target toxicities. Concurrently, non-covalent inhibitors of the KEAP1-NRF2 PPI interface, PROTAC degraders, and peptide inhibitors are entering preclinical and early clinical stages, expanding the therapeutic landscape into NASH, idiopathic pulmonary fibrosis (IPF), and CNS diseases.
Competitive Modality & Indication Snapshot
| Modality | Representative Players | Key Indications | Critical Assay Need (Why TarMart?) |
|---|---|---|---|
| Covalent Small Molecule | Bristol Myers Squibb (Reata), Biogen | CKD (Alport), Friedreich's Ataxia, NASH, Multiple Sclerosis | Cysteine reactivity panel (Need C151S vs WT discrimination via mass spectrometry) |
| PPI Inhibitor (Non-covalent) | Vividion, AbbVie, structure-based design groups | Oncology, COPD, CNS diseases | Binding affinity (Need high-purity Kelch domain proteins for SPR/BLI) |
| PROTAC / Degrader | Targeted protein degradation companies | Refractory cancers, context-specific Oncology | Ternary complex validation (Need full-length KEAP1 with intact BTB domain + CUL3) |
| Peptide/Protein Inhibitor | Academic labs, emerging biotech | Inflammatory diseases, IPF | KEAP1-NRF2 TR-FRET (Need high-purity Kelch domain and ETGE peptide) |
Key Functional Domains & Clinically Relevant Mutations
KEAP1 (Kelch-like ECH-associated protein 1) contains two primary functional domains: the BTB domain (involved in CUL3 binding) and the BACK domain (connector region). Key somatic mutations reported in cancer patients include:
- Breast cancer sample: somatic mutation (UniProt VAR_036084)
- Lung adenocarcinoma patient: somatic mutation (UniProt VAR_032102)
- NSCLC cell line: somatic mutation (UniProt VAR_032103)
These mutations may alter cysteine reactivity or protein stability, underscoring the need for high-purity WT and mutant KEAP1 proteins in validation studies,